Since quinoa contains twice as much fiber in comparison to other grains, it is recommended for problems like constipation, hemorrhoids, and for controlling blood sugar. Quinoa is rich in iron, a mineral that helps carry oxygen to cells and is critical for brain functioning, retaining body heat, and producing energy.
The list of benefits goes on and on. Rich in vitamin B2, quinoa supports energy metabolism in the brain and muscle cells. Since it is rich in magnesium, it might help migraine patients. As an antioxidant, quinoa protects cells against the negative effects of free radicals and slows down aging. It also contains quercetin, a good support against spring allergies. The lignin in quinoa is a good protector against hormonal cancers, such as breast cancer.
As the world population grows and the global climate changes, there is projected to be a decrease in the harvest yields of essential grains, like wheat and rice. Many experts believe that highly efficient plants like quinoa are the way of the future. They can be used to fight famine and help humanity adapt to a changing planet.

References
FAO Web Site. Corporate Document Repository "Quinoa (Chenopodium quince) http://www.fao.org

DaMatta F M, Grandis A, Arenque B C ve Buckeridge M S (2009). Impacts of climate changes on crop physiology and food quality. Food Research International 43: 1814-1823

Jacobsen,S.E. 2003. The worldwide potential for quinoa ( Chenopodium quinoa Willd.), Food Rev. Int. 19(1–2):167–177.

Comai,S., A.Bertazzo, L.Bailoni, M.Zancato, C.V.L.Costa and G.Allegri. 2007. The content of proteic and nonproteic (free and protein bound) tryptophan in quinoa and cereal flours, Food Chem. 100:1350-1355.

Despite that, there are more than 100 types of amino acids found in nature; only 20 of them are employed for protein synthesis. Among these 20 amino acids, excepting glycine, which does not display chirality, only the L-form of the 19 is used for protein synthesis. This is because ribosomes, where protein synthesis occurs, do not feature the utilization of D-form amino acids. As nothing in the universe exists in vain but with multiple tasks, D-amino acids have a job in the maintenance of life after protein synthesis in very different fashions. The way D-amino acids are employed in the execution and control of physiological preferences amazes scientists.

Up until recent times, D-amino acids were believed to be synthesized mostly by bacteria and plants, unlike mammals, and were considered dysfunctional as they passed, via consumption of nutrients, from bacteria and plants. However when D-amino acids were noticed for having roles as important as L-amino acids during the 1990s, the field gained significance. It was demonstrated that D-amino acids were found widely in invertebrates, vertebrates, and humans as free forms or inside proteins, undertaking critical functions in the nervous and endocrine systems. The most interesting point is the conversion of amino acids from the L-form into the D-form after the protein synthesis occurs in the peptides that are present in the venomous secretions of various animals. This conversion leads to the alteration of the peptide identity and function. Racemase and isomerase (epimerase) enzymes are utilized as they are created for this task. Usually, one or two amino acids of the D-form peptides are in D-form.

When chemist Gunther Kreil of the Austrian Academy of Sciences learned about the use of South American poisonous tree frogs (Phyllomedusa sauvagei ) during Shamanic hunting ceremonies by local Peruvian tribe (Matses), he studied this poison in detail. Participants of the ceremony first caused a burn on their chest region, then applied the poison they obtained from the frog skin over it. Diarrhea and tachycardia started within a minute, followed by a brief faintness. Once they recovered after a few minutes, they were to find themselves in a much more vigorous and exhilarated state of mind. The poison they were applying to their chest contained the dermorphin peptide, which has psychoactive, hallucinogenic effects and a D-amino acid. This peptide is a pain killer 30-40 times more effective than morphine. Among the 7 amino acids found in this peptide (heptapeptide), all are in L-form, except for one. Only the alanine, as the second in the peptide sequence, is in D-form and is produced via the isomerase enzyme from the L-alanine after the protein synthesis. G. Kreil discovered this D-form synthesizing enzyme in 2005. When this peptide was synthesized artificially in the laboratory, it did not display any biological activity or hallucinogenic effect. After a careful investigation of the case, it was found that frog skin based peptide had a D-form alanine second in its sequence; however, the one produced in laboratory had an L-form alanine. It was the presence of only one D-amino acid that made the difference in discovering the identity and function to the natural peptide in the poison.

In recent years dermorphin has started to be used as an illegal performance enhancer during horse races because of its pain killer feature. Horses on dermorphin can run longer and faster since they cannot feel the pain related to foot fatigue.

P. Kuchel of Sydney University also showed a D-amino acid presence in the peptide structured of the poison in the Platypus, a semiaquatic egg-laying mammal. Males use this poison as a weapon to fend off competitors. In 2009, Matthew Waldor and his friends at Harvard University discovered that the sugar-protein mix (matrix) called peptidoglycan found in the composition of bacterial cell walls is structured in a way to contain primarily D-alanine, D-methionine, and D-leucine. More interestingly, D-amino acids of the peptidoglycan structure were able to play a stimulatory role in coordinating the activities of other bacteria in the colony. For example, they acted as light houses in the use of florescence and helped in the formation of thin layers (bio-films) on various surfaces in bacteria. Once we understand the way D-amino acids help in communication between bacteria, it will be possible to use them as a drug. It’s possible they can be used to disintegrate bacteria that forms on teeth, in the lungs of cystic fibrosis patients, on clogs in fuel lines and water tanks, and in medical devices such as catheters.

D-amino acid containing peptides found in lobsters help maintain salinity levels and facilitate courtship in mating seasons. In recent years, D-amino acid containing antimicrobial peptides were discovered (bombinines) in the secretion glands of fire-bellied toad skins (Bombina sp). In this peptide, the second amino acid was in the D-form (D-allo-isoleucine). Two different peptides were found containing D-amino acids in the second position of the amino acid sequence of the poison secreted by Platypus males.

One of the reasons for D-amino acids to exist in animal poisons is that peptides containing D-Amino acids can not be easily degraded by the proteases (peptide bond breaking enzyme) of the host or opponents. Even though proteases can quickly and easily digest proteins composed of L-form amino acids, they struggle to do so with peptide bonds between D and L form amino acids. Pharmaceutical companies are trying to add D-amino acids to the peptide-structured drugs to prevent the quick degradation of peptides and proteins used for treatments when ingested. However, the addition of a D-form amino acid brings the high possibility of a situation that changes the function of a peptide or protein, or causes the loss of a protein. Nonetheless, specialists in this field point out that at least some amount of the D-amino acids that are produced by trillions of bacteria found on the skin, in the digestive track, and among other parts of the body can still be utilized for human health and convenience.

The D-serine of the mammalian nerve systems (glial cells and neurons), the D-aspartate of the neuro-endcorine, endocrine tissues, and testicles, and the D-alanine and D-aspartate amino acids of aquatic animals are abundant. D-Serine in the brain is synthesized by the conversion of L-serine into D-serine by the serine racemase enzyme. D-aspartate is in charge of hormone synthesis and secretion, and the regulation of spermatogenesis, and is produced by aspartate racemase and degraded by D-aspartate oxidase. It is also predicted to play role in the synthesis of hormones such as melatonin and testosterone.

As of now, four enzymes have been detected to be in charge of D-amino acid metabolism in mammals. How these are controlled is still unknown.

Publications pertaining to the association of epilepsy, schizophrenia, and bipolar disorders with enzymes in charge of D-amino acid synthesis and break down have increased in recent years. From this point of view, serine racemase and D-amino oxidase can be used to develop new potential drugs regarding the treatment of similar NMDA receptor associated diseases.

The first data demonstrating the use of D-amino acids in saliva in organs outside of the human brain was obtained by Y. Nagata and his team at the University of Nihon, Tokyo. A team led by Kenji Hamase of the Kyushu University discovered high levels of D-alanine storage in the beta cells of the rat pancreas. Kuchel, who discovered the enzymes converting the L-amino acids in to D forms in duck-billed Platypus poison, also found similar enzymes in the hearts of mice and humans. According to Kuchel, the physiological roles of those in humans remain to be unknown.

As a result, the common feature of toxins and antimicrobial peptides that are produced and secreted by animals is to contain D-amino acid. These peptides can be the source of a potential drug in the treatment of diseases such as cystic fibrosis, schizophrenia, and macular degeneration of the eye.

These prove that, especially in biology, exceptions are common; life is enriched via examples of extraordinary lives, processes, and mechanisms in unexpected places by unpredictable molecules or interesting reactions that can’t be predicted. Such discoveries help deepen our wonder at the intricacy and wisdom of creation.

Where am I?

There are 46 chromosomes in your body, carrying 20-25 thousand genes. Chromosomes and the genes they contain shape the genetic memory of a human being. Genes can contain hundreds of features, and these are revealed over time. For instance, you do not have any teeth when you are a newborn, but the time when you will get your teeth is encoded into your genetic memory. Once genes receive the action command, teeth start to emerge.

There are hundreds of genes located on chromosomes, all the way from the chromosome number 1 and 2, to chromosome number 46. For example, there are around three thousand genes found on chromosome number 1. The Y chromosome, in charge of male development, only contains 125 genes. A distinct address (locus) for each gene on the chromosomes is recorded. If you ask about the address of the fibrillin gene that synthesizes me, it is 15q 21.1, i.e., 15th Avenue, Long arm street, 21st pl, Number 1.

In other words my residing address is the 1st subband of the 1st band of the 2nd region located at the long arm of chromosome number 15. We are three siblings, known as fibrillin1, fibrillin2 and fibrillin3.

We stretch and relax like an arch. We can expand and tighten like an inflated balloon and then return to our previous state. If by an error, we happen to fail to restore ourselves after inflation, the tissue’s architecture gets deformed and expanded fibers cannot regain their original shape anymore. When observed in veins, this situation is called an aneurysm. The frequency of this disease is approximately one in ten thousand, which is also called ballooning. That said, my flexing is necessary. Veins flex so that the blood pumping through them doesn’t cause any turbulence, as it would otherwise be during a vacuum occurring inside metal water pipes. Flexible sportsmen who do acrobatic moves do not compare with me. I can bend, curve, flex, relax and constrict, inflate, deflate and transform like elastic, from one shape to another, for your health and overall convenience – all because of the wondrous features granted to my nature.

What kind of a fiber am I?

I provide structural support for the fabrication of elastic fibers in the connective tissue as a protein synthesized according to the code of the fibrillin gene. In case of my failure or absence, weaknesses occur, especially in the connective tissues of organs that are rich in elastic fibers, such as the aorta, lungs, and eye balls. The iris (the colored part of the eye), pupil, and eye lens display changes in accordance with levels of light or distance of objects observed. These changes are controlled perfectly according to my work, and humans often don’t even notice this. We also help the eye lens constrict and relax. It can be understood that we are such a great blessing granted for your service. Of course, if we tried to count all the blessings we’ve been given, and never even consider, it would be impossible!

My weight is 350 kilo daltons. A Dalton is an atomic mass unit approximately equal to one hydrogen atoms’ mass, which is 1.66×10-24. I consist of 2.871 amino acids. I am formed by the sequential arrangement of 20 amino acids that exist in your body as the smallest unit of proteins. We bind each other to become 10-12 nanometers wide microfibers as the result of a process called polymerization that brings loops of a protein chain together. These microfibers are brought together with the elastin protein that provides elasticity in our body. The system that we form with elastic fibrils constantly serves the body’s blood vessels, primarily the vessels located in your eyes, heart, and many of your tissues, such as your skin and nerves.

What do I do? We fulfill commands that are requested from us in many tissues and organs, without any flaws. Scientists call us the wonderful building blocks of the body’s architecture. We can extend twice as much of our length. We are always on task: while you are breathing, when your heart is pumping blood and your stomach is digesting food, or the moment you are gazing at nature with your eyes. We are given the duty to prevent many organs from tearing, including the heart, lungs, stomach, and blood vessels. One of the places I work most frequently is the aorta, the body’s major artery. Your heart beats approximately a hundred thousand times a day. A high level of pressure develops in the arteries during the pumping process. You would suffer greatly without the help of our elastic fibers. Blood vessels would rupture, ending your life. This high pressure is tolerated only through the expansion of the vessel’s diameter without any decrease in length of the artery. This diameter regulation is designed so wondrously that blood flow remains the same; no shaking or waves are observed. This diameter control happens via the fibrillin protein located inside the vessel.

I also play a role in the vitality and tension of your skin. Skin is essentially a dense fibrous connective tissue composed of a protein called collagen. I am also one of the main elements of this connective tissue. As you age, this layer starts to dry and has lesser fibrous proteins; therefore, as fibers decrease, so does my tension, and I start to wrinkle. Elderly people do not like getting wrinkly, but this is your fate. Whatever you do, I will also age and die.

I cannot go without pressing this important issue: Staying under the sun for a long time degrades me. If done properly, sun light is useful for skin. But solar radiation damages the live tissues and organs. This radiation is an effective factor both in degradation of protein structures, and the formation of varicose veins and skin damage. It is reported in various sources that exposure to sun rays leads to alterations in the genetic material of skin. Ultraviolet rays speed up the degradation of skin. In medical language, this is called oxidation via free radicals. Please do not burn us and yourself while sunbathing. Even if you do not care for yourselves, you should still be considerate of us. If you say that sunbathing both helps, with vitamin D synthesis and reducing the risk of osteoporosis, I would like to remind you that for the vitamin D synthesis of skin, it is sufficient to expose your hands, feet and face to the sun.

How is life without me?

Though we were wisely designed, sometimes, you are tested by certain diseases in which we are not present. Absence, as they say, makes the heart grow fonder!

Life without me is unbearable. I could give a couple of examples, should you like. If I was not created, your skin would not be flexible. You wouldn’t be able to control your eye lenses. Your aorta would not be flexible and your heart, which beats thousands of times a day, would be torn under the high pressure in a short amount of time. Major problems would occur with the development of your stomach, lungs, and other organs.

I also have a significant job keeping TGF-Beta (which helps cells grow) function under control. To give you an idea of how important this is, imagine your communication system turned upside down. Now imagine how complicated are the communication systems connecting billions of people around the world, how a mess it would be when they are out of service. These are nothing when compared to the human body. There are 100 trillion cells in the human body, communicating with each other instantaneously. A cellular community that is fifteen thousand times more crowded than the earth’s population communicates via small molecules, like us. Cellular proliferation and tissue differentiation would fail if cells failed to communicate. The full spoon of food in your hand would not end in your mouth but maybe in your ear or your eyes.

If a mutation happens with the Fibrillin-1 gene, Marfan syndrome can occur. This disease, which was defined in the 1800s, is named after its discoverer. The frequency of this disease is one in five thousand. One of the major lethal consequences of Marfan syndrome is an aorta tear. This is in addition to many problems with the eyes, skeleton, and cardio-vascular systems. Many of the patients die in their 30s or 40s because of the flaws in the cardio-vascular system. Of course, death may occur at any age because of an aorta rupture. 14% of the patients with Marfan syndrome display chronic obstructive pulmonary disease (COPD), which is associated with breathing problems, because the integrity of lung tissue is compromised. Another disease I help prevent is called Ektopia lentis, in which the eye lens is displaced from its original position. Normally, I help eye functioning. When my fibers relax or constrict, depending on light, I help the eye to relax, enabling both near and far sightedness. With Ektopia lentis, anomalies on the front vestibule of the eye, a high degree of myopia, and retina damage occur.

If overproduced, I can cause another problem with the eye, called exfoliation syndrome. This is when fibrous connective tissue, like me, accumulates in the eye – it’s commonly called glaucoma, or ocular hypertension. In some people, as they age, a fibrous material like hair dandruff collects on the eye lens. This material, dislocated by movements of the iris, blocks the drainage channels that discharge the intraocular fluid. Eye pressure increases as the result of failed drainage. As you see, I am not a problem when I am synthesized normally, but can be trouble if over produced! My final request from you!

You have seen our amazing works and complicated functions. Therefore, please remember me and my friends. Please do not ignore our efforts and activities. Be grateful for the blessings provided through us, even if you can’t see them. And take care of us, please – don’t get carried away with too much tanning!

The first is the preservation of characteristic, long term data imprints that describes the development of an organism in the stable DNA sequences.

Second is the storage of medium term epigenetically featured data that is carried a couple of generations further down the cellular level. Epigenetic information is not stored within nucleotide sequences but in the chemical modifications of these sequences (like the methylation of repeated strings of GC dinucleotide).

Third is the storage of data generated as a result of dynamic interactions between proteins, RNA and DNA in order to adapt to the events and changes during cellular life cycle in the form of nucleoprotein or DNA-protein complexes.

The data generation and storage capacity of DNA in three different hierarchical levels and time periods demonstrates that genome plays a plethora of roles in cellular activities and heredity. Formatting of genome for its generation and storage of data is carried out via DNA sequences of various features. Genomic system is composed of repeating DNA sequences. DNA sequences (satellite) function as a marker as they repeat numerous times in various frequencies. Genome includes genomic folders similar to that of computer systems. These genomic folders, also known as the epigenetic index of genomes, are responsible for the remodeling of chromatin and the coordinated control of genomic functions. Repeating DNA sequences play a critical role in replication of genome (making a copy of DNA), dispersal of copied DNA into daughter cells and construction of support systems that enable organization of chromatins.

It is possible to better understand genomic functions in relation to examples such as memory sticks and hard drives that are used in electronic information systems. The difference between a genome as a basic data-information storage medium from a hard disc is that it can be replicated as required by its nature and these replicas can be transferred to daughter cells. Following examples could be given to illustrate that a genome gains function only when it interacts with various data processing modules in the cell.

1. A copy of genome is produced by cellular DNA replication system
2. Correct localization of each genome copy towards daughter cells is only possible when chromosome segregation system works (the centrosomes and microtubules)
3. The central transcription system is responsible for the copy of data from DNA to RNA. Different gene expression patterns are developed via regulation of transcription time and level with the help of transcription factors and a web of cell signalization.

Very intricately organized genomic system structures are designed through the successive combination of protein encoding sequences, signals distributed in various places and repeating DNA sequences. Formatting of genome resembles formatting of computer programs. Various repeated serial commands of computer software are used to allocate addresses to files independent of the original data contained; different computer systems use different signals and structures to manage programs. In a similar fashion, diverse living species often utilize repeating DNA sequences and chromosomal structures to organize the encoded information and to format their genomes.

Diversity and variation of repeating DNA sequences are building blocks that are constructed into different genomic system structures. Genomes of different organisms bear characteristic system morphology just like computers with various operating systems and hardware. For instance, animal cells are created as a good model to take and incorporate foreign DNA into their genomes. Genetic data transfer among organisms of the same kind is referred to as “vertical gene transfer” whereas transfers between different species, genuses and classes are called “horizontal gene transfer.” Mobile DNA sequences like transposons are very effective horizontal gene transfer agents.

Cellular differentiation and morphogenesis (formation of tissue and organ from cell) is not programmed completely in the primary structure of the DNA sequence. Components of modular programs are encoded in a flexible way and a continuous renewed and recombined arrangement is enabled when needed.

The reason behind creation of different organisms from a single genome is this utilization of such genomic structure. Metamorphosis, that is the development of different organisms like invertebrates such as a caterpillar and a butterfly, is a good example of this feature.

Two organisms from the perspective of the same genomic protein and RNA codes can be considered as two different species. Different genomic structures and repetition of sequences among different organisms are distinctive criteria for the identification of species since these features can lead to mismatch of reproductive cells, different expression patterns of genetic code sequences, and may cause ecological diversity as well. That is why repeated DNA sequences are very important in studying parental relationships. Today, microsatellite DNA as repeated DNA sequences are used to configure biological relations among individuals in forensic sciences. Plant species vary in respect to the repeated sequences in centromeres in their chromosomes; these variations are used for identification of species. Main determinants of genomic system structure are diversity, frequency, and genomic localization of repeated DNA sequences. To explain this with examples, we could say that successively repeated sequences at centromeres, telomere repetitions and transcription, packing of chromatin, repeated sequences that are spread throughout genome in charge of cellular functions like nucleus localization are the main elements of the genome system structure. Genome is a single integrated system that is controlled closely and remotely via communication webs that use repeated sequences.

While explaining the Qur’anic concept of the Manifest Record (36:12) Bediuzzaman Said Nursi, the great renovator of Islamic thought in Turkey in the twentieth century, wrote that the Manifest Record expresses one aspect of Divine knowledge that is related “more to the past and future than to the present. It is a book of Divine Destiny that contains the origins, roots, and seeds of things, rather than their flourishing forms in their visible existence” (30th Word, Second Aim).

Inspired from this view, a seed can be considered as a tiny adorned form of Divinely creative command as programs and indexes and as a determinant for those programs and indexes in the organization of an entire tree. Since the Manifest Record book, as a title of Divine knowledge and command, observes the past and the future rather than the present, the genome of a grain or a seed acts like a library and an archive in which the future and past of an organism is written.

Sequences encoding different information in DNA

Different information types corresponding with various DNA sequences exist in the genome. These DNA sequences that were considered junk for a long time because they were not coding proteins, have in fact been found to be responsible for an amazing array of functions in genomic structure. Some of these sequences include:

1. Group determining sequences that enable coordinated or successive expression of genes,
2. Sequences acting as a marker in charge of initiation and termination during transcription of DNA to RNA ,
3. Signal sequences responsible for conversion of primary immature RNA, sequences into smaller functional RNA molecules,
4. Transcription control sequences that determine the expression frequency of genes,
5. Sequences that identify and mark the initiation regions for intensification and remodeling of chromatins,
6. Sequences that make binding regions which affect the relocation of genome in nucleus or nucleolus,
7. Sequences that target regions where covalent DNA modification (methylation) with functional groups like methyl takes place,
8. Sequences that control and identify the regions responsible for initiation of DNA replication,
9. Sequences that make the structures which enable completion of replication at terminal ends,
10. Sequences at the segregation points that enable equal distribution of copied DNA molecules into daughter cells and centromere sequences,
11. Sequences responsible for guidance during repair of DNA bound errors and damages,
12. Start point sequences used for repackaging of genomes,

Recurring sequences exist in the genomes of many organisms and shows great structural diversity. Recurring elements function as an initiator or terminator for heterochromatin regions. Furthermore they form an important scaffold and binding spots for folding of DNA structure. As if they carry out the job of an architectural mold in specific shaping of genome to be packed into a very limited area. The ratio of repeating sequences in genome (60-90%) is much more than sequences that are encoding proteins and RNA (10-40%). To explain it with an example, chromosomes in human genome are made up of packages of protein-DNA such as heterochromatin and euchromatin. Heterochromatin regions usually make up the regions with no transcription whereas euchromatin regions feature DNA transcription.

The ratio of protein encoding sequences to the entire human DNA is approximately 1.2%. Around 43% of euchromatin regions are composed of recurring and mobile DNA elements. 18% of heterochromatin region is also made of satellite (dense repeating sequences) and mobile DNA elements. Therefore almost 50% of human genomic DNA is composed of these repeating DNA sequences. In bacteria however, these only make up around 5-10% of the genome. These sequences were described as parasitic and junk individual DNA structures up until today and still continues to be described thus by many researchers and scientist. Nevertheless, even today, mobile DNA elements and repeating sequences are accepted as genomic parasites. Recent advances in the last ten years that have demonstrated this is not true, have instead revealed the vital importance of repeating sequences in genomic functions.

Repeating DNA sequences affect chromatin (dense pack of DNA and protein) structure in two ways. Irregular repeating DNA sequence copies contain binding regions for proteins that organize DNA. Heterochromatin (darker since it is densely packed chromatin) inhibits transcription and recombination, delays replication, and generally blocks the reading of information in DNA sequences that contain genetic coding. Heterochromatin regions are distributed throughout the chromosome. Because of this, presence of regions with coupled successive repeated sequences triggers heterochromatin formation.

In fruit flies, placement of protein encoding loci required for eye pigmentation near the heterochromatin blocks in centromeres (phenomenon of position effect) is provided via organization of chromosomes and thus, formation of phenotypic characters are inhibited. The “phenomenon of position effect” is convincing evidence that genome is a major system which is integrated with composition of partially repeating DNA sequences. When heterochromatin amount is increased in XYY male fruit flies, reorganized pigmentation of eye expression decreases. In XO males, when heterochromatin amount decreases, inhibition becomes severe. Changes in levels of protein which binds to special heterochromatin specific DNA regions generate opposite effects. Decrease in these proteins reduces or suppresses “phenomenon of position effect.” Surplus synthesis of these proteins also enriches this effect.

Repeating DNA sequences play an important role in the transfer of genome into daughter cells. For instance, they function in formation of the centromeres as chromosomal binding regions for microtubules, during gamete formation as linear terminals of chromosomes are replicated, and during chromosomal matching. Distribution of repeating sequences plays a major role in configuration of genomic functions. Each genome has genomic system structure that is shaped dependent on the amount of repeating DNA sequences to a major extent.

Going back to Nursi’s explanation of the Manifest Record, we can draw a parallelism between the book of the universe and the book of revelation, the first of which shows us that certain sequences in the genome are repeated for significance and necessity, just as many verses are repeated frequently in the Qur’an with nuances to refer to different meanings, benefits, and purposes, opening a wider space for many interpretations.

A genome is not only a book that contains protein and RNA codes, but also has a complex system structure with many functions for cellular vitality. The most needed sequences are those that are repeated more frequently. They are not pieces of junk DNA as predicted, they are jewels Divinely constructed.

References

• Shapiro J. A. 2001. “Genome Formatting for Computation and Function :Genome Organization and Reorganization in Evolution: Formatting for Computation and Function.” Presented at a symposium on “Contextualizing the Genome,” Ghent University, Belgium, November 25 – 28, 2001 (Ann. N.Y. Acad. Sci., in press)
• Shapiro, J.A. 2005. “A 21st century view of evolution: genome system architecture, repetitive DNA, and natural genetic engineering.” Gene 345, pp: 91–100.
• Shapiro J. A. and Sternberg R. V. 2005. “Why repetitive DNA is essential to genome function.” Biol. Rev., 80, pp. 1–24. Cambridge Philosophical Society.

The cell is the structural, functional, and biological unit of all organisms. All information needed for numerous processes in a cell, including repair and division, is contained in DNA (Deoxyribonucleic acid). DNA is a huge single molecule with intriguing features. How can a single molecule have such a dominant role in preserving information essential for the continuation of life? What are the mechanisms and levels of organization during its function? What does DNA mean for a single cell or for a human being? It’s impossible to answer these great questions in a single article; however, understanding the ways DNA exerts its role, DNA’s impact on multiple levels ranging from a single cell to an organism, and coordination between various levels, can potentially open up new frontiers in our mind and in our perception of life.

“Double helix” architecture of DNA DNA has an elegant structure that forms the basis for all of its functions. DNA is a repeating structure of nucleotides. Each nucleotide is formed of a phosphate group, 5-carbon sugar (deoxyribose) and a nitrogen-containing base attached to the sugar from outside to inside (See Figure 1a for a schematic view of DNA). There are four types of nucleotides in DNA, differing only in bases. We can consider bases as the identity of nucleotides. These four nucleotides are shown with letters A (adenine), T (thymine), G (guanine) and C (cytosine). Thousands of nucleotides bound with sugar-phosphate covalent bonds come together to form long strings. The sugar-phosphate backbone can be imagined as the steelwork of a skyscraper. The nice thing about nucleotides is their specific match to each other in double helix. A forms a base pair with only T, and G forms a base pair with only C. These pairs are bound to each other with hydrogen bonds. This feature is the key that makes DNA a double ladder. Two strings of nucleotides form a double helix by selective interactions of As with Ts, and Gs with Cs (See Figure 1b for 3-D structure of DNA). In DNA structure, hydrophobic bases tend to stay inside of double helix and hydrophilic sugar-phosphates stay outside interacting with water in nucleus. This feature helps DNA to form a double ladder. The length of the sugar-phosphate backbone is more than the bases. To compensate for the length difference, the sugar-phosphate backbone wraps around the bases inside, as a road wraps around a mountain to climb to the top. This simple difference is the main reason for DNA to form a helix.

The double-stranded nature of DNA with specific base pairing is one of its key features as genetic material. DNA is replicated using one strand as a template. Replication machinery reads one strand of DNA and builds the second strand by putting As against Ts and Gs against Cs. If a mutation occurs in one strand, it can be repaired using the second strand. This system is like photocopying DNA from itself instead of building it from scratch every time. That is why specific base pairing of nucleotides in the double helix makes it possible to replicate DNA through generations, protecting its integrity and information content. The code of DNA, an alphabet with four letters DNA contains the information to produce nano-sized cellular machineries called proteins. We mentioned that there are four types of nucleotides. Nucleotides are like letters in DNA, three of them are code for one amino acid of protein. We can make it more understandable by giving an example: “ATG-GCC-CTG-TGG-ATG” as a nucleotide sequence of DNA corresponds to the first five amino acids of a protein called insulin (a hormone regulating blood glucose level that is important in diabetes) and amino acid sequence is methionine-alanine-leucine-tryptophan-methionine. The code is so sensitive that even a single mistake in the sequence of DNA can cause serious diseases in humans such as sickle-cell disease or cystic fibrosis. With all these nucleotides, DNA can be thought of as a book containing amino acid sequence information for thousands of proteins (about 30,000 in humans). The amount of information contained in DNA is incredible: a typical human cell contains 2 meters of DNA that is tightly packed by proteins in the nucleus. If we tried to write the information from DNA into books, the book would contain over one billion words and 1,500,000 pages. DNA-protein interdependency and the cell as a micro-factory DNA can be thought of as an instruction manual that stores information for proteins and RNAs. Proteins, as molecular machines, perform particular tasks such as energy production and synthesis of DNA and RNA (See Figure 2 for the structure of proteins). Certain proteins read the information on DNA and make a transient copy of certain regions of DNA. These copies are called messenger-RNAs (mRNAs) and mRNAs are transported from nucleus to cytoplasm (See Figure 3 for representation of mRNA production from DNA by proteins). In cytoplasm, the information on mRNAs is read by protein complexes called ribosome. Ribosomes produce new proteins processing the data from mRNAs. This information flow from DNA to proteins is called central dogma in molecular biology (Figure 4). The data that is encoded in DNA can be read, translated, and put into the form of product only by proteins. We can conclude that for a protein to be produced, DNA is essential; for DNA regions to be read into proteins, proteins are essential. So, there is interdependency between proteins and DNA. Proteins without DNA have no future and no ability to regenerate and DNA without proteins is just like an instruction and manufacture manual of a computer without the user and computer itself. We can imagine the cell as a sophisticated factory, and proteins as the machines of the factory. DNA includes the instructions for the factory to be rebuilt and for itself to be rewritten for every new factory. It has instructions on how to build every machine in the factory. It has also codes for when and how much of these machines should be produced (we will discuss more about these codes on DNA in the next section). On the other hand, the timing and control of all these productions also depend on machines in the factory. Some of these machineries read and decode the instruction manual, some of them produce new machines by reading the decoded copies of the instruction manual, some of them act as sensors for the signals, some of them transmit signals to other machines, some of them produce signals by measuring the levels of materials in the factory, some of them function in communication with other factories, and so on. As we can see, DNA and proteins are meaningful for life only when they are together in the excellent cell context. This is a perfect example of the principle that the whole is bigger than the sum of its parts, because each element of the cell system has limited potential, until it comes together with the others to blossom into life.

The famous term “Gene” We can think of genes as functional units of DNA. A gene has the information content for at least one protein. Humans have about 20,500 genes that are read by protein machineries to produce proteins. Special proteins read the information on genes and make a transient copy of these certain regions of DNA. The process of making a copy of a gene as an mRNA is called transcription.

Genes don’t only store information; they have an intrinsic architecture of design to coordinate transcription utilizing three main components: promoter, coding region, and terminator. The promoter is the gene region that signals for the start of transcription. Protein machineries bind to the promoter and activate transcription. The coding region has the information for the amino acid sequence of the protein. The terminator region gives the stop signal for transcription. There are different functional regions on DNA located between separate genes such as enhancer regions that are platforms for binding regulatory proteins to tune the transcription.

The coding region of genes has multiple reading blocks for amino acid sequences and these reading blocks are called as exons. For some genes, different combinations of exons can be put together to give rise to different proteins. This mechanism allows one gene to be able to produce multiple proteins, increasing the efficiency of genetic material. A similar mechanism is used to produce antibodies (proteins recognizing foreign antigens) by the immune system. Different regional genes come together by a mechanism of DNA rearrangement (V(D)J recombination) and their differential combinations form many different antibodies. For example, a part of the antibody that is called a heavy chain is produced by a DNA region containing 65 variable (V) genes plus 27 diversity (D) genes and 6 joining (J) genes (5, 6). This produces a combination of 65 V genes x 27 D genes x 6 J genes = 10,530 heavy chains. There is a similar mechanism of rearrangement for light chain and variable region of antibodies, which result in millions of different antibodies for host antigens. A single example in the immune system shows us that DNA not only has a decent design for the coding system, but it also has ingenious and creative mechanisms to maximize its potential.

Gene expression is orchestrated during development and formation of organs The human body which consists of more than 1013 (ten trillion) cells is generated from a single cell called the zygote (see Figure 5). This tells us that, in a single cell, all the information and instructions to build and coordinate the systems of human body is encoded. Different tissues and organs including muscles, nerve cells, connective tissue, and eyes are fruits of one single cell. They all contain the same genetic information. Then what makes them different?

Promoters, enhancers, and repressors located in and nearby genes are important in spatial and temporal control of gene expression in different cell types of the body. Each cell type in our organs expresses a different subset of genes; this is what gives a cell its identity. For example, in muscles, myosin is expressed and in the eye’s retina, rhodopsin is expressed. Myosin functions in contraction and rhodopsin functions in vision. What determines the expression of rhodopsin in the eye but not in a muscle? The determination process occurs during development by programmed interactions of specific proteins called transcription factors, and restricted regions of DNA including promoters and enhancers. During development, certain regulatory proteins in a specific cell type, bind to DNA regions of only some genes (for example, in future retinal cells of the eye, rhodopsin gene would be activated but not myosin) and this predetermination orchestrates differential expression of genes to give rise to hundreds of different types of cells.

Different layers of complexity and organization related to DNA

There are different layers of function for DNA—each subtitle of this article tries to focus on a certain layer of function. DNA as a molecule has a double helix structure and is replicated through generations to preserve genetic information. It stores genetic information and has a four-letter alphabet for the expression of proteins. In the second layer, DNA has an informational unit called gene and thousands of genes are encoded in DNA to contain information for proteins. Each gene is controlled individually by making use of promoters and enhancers. In the third layer, all processes in the cell micro-factory as an entity are performed through interactions of DNA and proteins with each other and among themselves. Proteins read DNA code and work as cellular nano-machineries. In another layer, temporal and spatial expression of genes on DNA are orchestrated and different subsets of genes give rise to different cell types and organs. Organs communicate with each other to function properly and keep the balance and homeostasis of the body. The information stored in DNA not only coordinates highly sophisticated processes of a single cell, it simultaneously projects the whole body system of a human being, which is billions times bigger than a single cell.

DNA functions in all these different layers and keeps a great harmony in coordination between various layers of function. After grasping this complexity, organization and communication from a single molecule, to proteins, to a single cell, to tissues and organs, and to a human being by utilization of DNA, should not we ask ourselves, “can these elements come into existence by random forces and collisions?

References

1. Calladine, C. R. et al. 2004. Understanding DNA: The Molecule and How It Works, Academic Press

2. http://www.genome.gov

3. Li A, Rue M, Zhou J, et al. 2004. “Utilization of Ig heavy chain variable, diversity, and joining gene segments in children with B-lineage acute lymphoblastic leukemia: implications for the mechanisms of VDJ recombination and for pathogenesis.” Blood 103 June (12): 4602–9.

A particularly interesting class of all these non-coding RNAs comprises riboswitches. Riboswitches are structured mRNA elements that regulate gene expression upon binding of a specific small metabolite. These biosensors were first discovered in 2002 in bacteria. Later, it was shown that plants, green algae and fungi also posses riboswitches. Although, only one type of riboswitch is found in plants and none has beeen detected in mammals yet, metabolite-sensing riboswitches are commonly used for the regulation of fundamental biochemical pathways in bacteria. Riboswitches help cells monitor the environmental conditions and determine if a compound is present at sufficient levels or not. Based on this decision, production, degradation or transport of the related metabolite is either turned on or off.

Architecture of a Riboswitch

A standard riboswitch is divided into two parts: a ligand-binding domain and a gene expression domain (Figure 1). Small molecular metabolites bind to the ligand-binding domain, which is called aptamer, of riboswitches with astonishing specificity. For instance, purine riboswitches differentiate guanine from adenine by at least 10,000-fold based on the identity of a single pyrimidine (thymine or cytosine) that binds to the ligand (1). When a ligand binds to aptamer, conformational changes of the RNA’s structure occur at the gene expression domain. Eventually, this leads to the modulation of gene expression. Some of the riboswitch mechanisms to regulate the expression of genes include formation of stem-loops, lollipop-like RNA structures, which lead to the blocking of transcription or translation, which are the processes where proteins are synthesized using the mature mRNA, self cleavage or mRNA destabilization (Figure 2).

Classes of Riboswitches

The numerous distinct classes of riboswitches discovered so far are differentiated by their ligands and remarkably, the same class of riboswitches can control gene expression through different mechanisms in various organisms. For example, a riboswitch that recognizes and binds thiamin pyrophosphate (TPP), a derivative of vitamin B1, is called as TPP riboswitch (2). In plant cells, when TPP levels are high, excess TPP binds to a TPP riboswitch located in one of the TPP biosynthesis genes. As a result of TPP binding, conformation of that RNA segment changes, which leads to the formation of an unstable mRNA product which degrades quickly. Although, a very little amount of stable mRNA is also produced, it is not enough for the protein synthesis of an important component of TPP biosynthesis. Therefore, TPP biosynthesis can not be completed and consequently TPP levels drop in the cell. On the other hand, when TPP levels are low in plants, more stable mRNA is formed because there is not enough TPP that can bind to the riboswitch and cause structural changes which will result in the formation of unstable mRNA. The stable mRNA produced in the absence of excess TPP is used for the protein biosynthesis of TPP metabolism successfully and thus TPP levels increase in the cell. Unlike plants in bacteria, when TPP concentration is high, riboswitches down-regulate expression of thiamin biosynthesis genes by either blocking the formation of any type of mRNA (both stable and unstable) or preventing the mRNA process rather than destabilizing the mRNA. Some of the other riboswitches that bind vitamin derived compounds are adenosylcobalamin, the coenzyme form of vitamin B12, and flavin mononucleotide, a biomolecule produced from vitamin B2, riboswitches. There are also riboswitches that can bind to amino acids such as lysine riboswitch. The cyclic diguanylate (c-di-GMP) riboswitch is the first known example of an RNA that binds a second messenger, which carries signals from receptors on the cell surface to target molecules inside the cell (3). Purine riboswitches selectively recognize guanine or adenine and regulate purine biosynthesis and transport, which is important for DNA/RNA synthesis. Another interesting type of riboswitch is the glmS riboswitch. It modulates gene expression by undergoing self-cleavage when there is a sufficient concentration of glucosamine-6-phosphate, an important amino sugar. The spectrum of ligands that can be recognized by riboswitches also includes a metal ion, as well. Mg(2+) riboswitches control Mg(2+) transportation when cells are grown in high Mg(2+) environments. In brief, the growing list of studies on riboswitches shows how novel mechanisms are which they use to regulate the gene expression of many fundamental metabolic pathways.

Applications for Riboswitches as drug targets and chemosensors

Riboswitches are powerful and essential components in all three domains of life which are bacteria, archaea (a group of single-celled microorganisms) and eukaryotes ( organisms whose cells contain complex structures inside membranes such as plants and fungi) functioning as intracellular biosensors and regulators. They regulate gene expression in a highly efficient, precise and fast way. Therefore, they can be engineered for various applications.

First of all, riboswitches are excellent candidates as drug targets since they control many important bacterial and fungal genes. Chemical analogs that mimic the actual ligands of the riboswitches can be designed to silence or regulate the expression of defective genes responsible for disease development or even kill certain bacterial pathogens by turning off the genes that are involved in fundamental metabolic pathways. A great example of this strategy is presented by the Breaker laboratory at Yale University. The Breaker group chose guanine-binding riboswitches as targets for the development of novel antibacterial compounds. They have designed several guanine analogues and tested their ability to be bound by the riboswitch and repress bacterial growth (4). They have been able to inhibit the bacterial growth by inducing guanine riboswitch action. Their approach could be used to discover new antibacterial compounds that specifically target other riboswitch classes.

In addition to being drug targets, riboswitches can open new frontiers in bioremediation, bionanotechnology, and synthetic biology. In 2007 Shana Topp and Justin P. Gallivan from Emory University demonstrated that Escherichia coli can be reprogrammed to detect, follow, and precisely localize to a completely new chemical signal by using a synthetic riboswitch (5). They suggest that the bacteria with synthetic or mutated riboswitches could be used to follow and degrade pollutants in soil or target small-molecule signals of disease. Overall, their work to equip the bacteria which can autonomously follow chemical signals, degrade, synthesize or release compounds can help scientists invent new technologies in bioremediation, drug transport, and synthetic biology.

Furthermore, riboswitches are ideal candidates for use in analytical devices and techniques. Their binding features make them suitable in all specific analytical applications in which selective recognition is required. Therefore, these powerful molecular tools can be utilized in analytical chemistry, molecular biology and biosensor technology (6).

As a result, living systems utilize riboswitches to detect the concentrations of small-molecule metabolites and to modulate the expression of related genes via numerous elegant mechanisms. The use of genetic engineering of riboswitches holds enormous potential for inventing new applications to sense and destroy pathogens, deliver drugs, perform bioremediation, detect chemicals and many others that might have significant impacts on our lives. It is also remarkable that only a couple of decades ago most of the non-coding RNAs were assumed to be useless, and are called junks since they do not provide any information for protein synthesis. Yet riboswitches by themselves are enough to prove that God has created everything with a purpose. He is All-Wise and he does nothing in vain. Riboswitches are not useless at all. They are such complex, and perfectly working systems that they can serve humanity as well-designed on/off switches in numerous applications.

Safiye Arslan is a research fellow in the area of biological chemistry and lives in Nevada.

References

1. Gilbert SD, Reyes FE, Edwards AL, Batey RT. 2009. Adaptive ligand binding by the purine riboswitch in the recognition of guanine and adenine analogs. Structure 17, 857-868

2. Wachter A, Tunc-Ozdemir M, Grove BC, Green PJ, Shintani DK, Breaker RR. 2007. Riboswitch control of gene expression in plants by splicing and alternative 3′ end processing of mRNAs. Plant Cell 19, 3437-3450.

3. Kulshina N, Baird NJ, Ferré-D’Amaré AR. 2009. Recognition of the bacterial second messenger cyclic diguanylate by its cognate riboswitch. Nature Structural & Molecular Biology 16, 1212-1217.

4. Kim JN, Blount KF, Puskarz I, Lim J, Link KH, Breaker RR. 2009. Design and antimicrobial action of purine analogues that bind Guanine riboswitches. ACS Chemical Biology 4, 915-927.

5. Topp S, Gallivan JP. 2007. Guiding bacteria with small molecules and RNA. Journal of the American Chemical Society 129, 6807-6811.

6. Mairal T, Ozalp VC, Lozano Sanchez P, Mir M, Katakis I, O’Sullivan CK. 2008. Aptamers: molecular tools for analytical applications. Analytical and Bioanalytical Chemistry 390, 989-1007.

Decisions within the cell: mathematical and algorithmic character

In order to enable Escherichia coli bacteria to use lactose (disaccharide), the genetic information of the enzymes that have role in transporting the lactose into the cell and converting it into glucose is coded in the bacteria’s genome. The binding and decoding structure which enables the genes to be transcribed at the right time in the appropriate amount is called the operon. The operons are model mechanisms which work on the synthesis or destruction of every chemical molecule (metabolite). One of these, lactose operon, is a good example that demonstrates how the decoding information contained in DNA is regulated and controlled in the bacteria. E. Coli is equipped with a system that distinguishes lactose and glucose when they are combined and this system functions perfectly. Primarily, all of the existing glucose is consumed before the start of the production of those enzymes that splits lactose into glucose and galactose. It has been discovered that this operation in the bacteria is followed by an interaction between DNA sequences located on the upper part of the lactose gene and various molecules. The DNA sequences on the upper part of the gene are the signals that format DNA for transcription. These signals cause the decoding of the genes that interact with the transcription factors. While some of the signals in the relevant region of the genes are common in most genes, some others are specific.

The most basic interaction system of the genome-proteome (all proteins in cell) is the suppression of the lactose operon that is observed in E. Coli. This process depends on DNA-protein interactions which are based on a mutual relationship and it requires the existence of repeated DNA sequences. Tetramer lac1 protein control the lac operon binds to four repeating binding regions on the DNA. Since one dimer can be connected to one operator sequence, two dimers are connected to two operator region units, and as a result the result is a loop formation in the DNA structure. Consequently, because of the access of RNA polymerase to the promoter region, the pre-coding process of genes is hindered. If the hindering protein is in the form of a monomer, the operator displays a weak interaction with half of the sequence. In the dimer form there is a stable binding. For this reason, many procedures in the cell occur by working together and making a union of molecules. Since the loop shape of DNA stabilizes the structure, it prevents the RNA polymerase from being connected to the promoter region. In order to eliminate the blockage on the lac operon, the mutual relationship must be prevented by stimulatory molecules, such as lactose.

There is metabolic information in cells that measure and control the physiological condition. The sequences on the regulatory region of the lactose operator and the data concerning the physiological condition of the lactose and glucose metabolisms are analyzed in the cell which perceives the presence and the amount of glucose through the changes in the system that transports the glucose into the cell. The molecule that announces the presence of glucose in E.coli is cyclic-AMP and concentration of this molecule in the cell is inversely proportional to glucose. The level of this signal affects both the coding and regulation of genomic information. The protein that transports glucose into the cell contains a phosphate group; as it transports glucose into the cell, this carrier protein phosphorylates the glucose molecule thereby loosing its phosphate group. As a result, the proportion phosphorylated transport protein and those without phosphate provides information about the glucose level in the cell. The phosphorylated form of the carrier protein activates the adenosine cyclase enzyme. Through this enzyme, ATP is converted into cyclic-AMP. The cyclic-AMP level increases in the cell. Consequently, the situation that concerns the increasing concentration of the phosphorylated transfer protein and the cyclic-AMP is interpreted as non-existence of glucose in the cell. The CRP protein that binds to regulatory region of the lactose can only bind to this region in the presence of cyclic-AMP. The cyclic-AMP-CRP complex which is tied to the promoter region of the lactose gene speeds up the transcription of the lactose operon. Transcription rarely happens when there is no lactose. This is because the lactose repressor protein lacI, hinders the RNA polymerase reaching the lactose promoter region by binding to the operator of regulating region. The cell can sense the existence of lactose in a circuitous manner. Low levels of coded Permease enzyme on the lacY region transfer some lactose into the cell. The coded beta galactosidase on the lac Z region alters them into a sugar called allolactose. The allolactose is bound to the lacI repressor protein and changes its conformation. The allolactose –lacI repressor complex can not bind to the operator region. The promoter region, called LacP, of Lactose operon is set free for transcription. In fact, every one of these molecular interactions is an incident of information being transferred. All these incidents demonstrate that an algorithm (If there is no glucose and only lactose exists, then transcribe the lacZYA enzyme) that is able to distinguish the difference between two sugars exists in bacteria cells and that it functions perfectly.

In short, the signal transfer in lactose operon occurs with the activation of chemical molecules that represent the experimental data pertaining to the physiological environment of the cells. For example, the levels of cyclic-AMP, allolactose and protein phosphorylation indicate the existence of glucose and lactose. The regulating network system, on the other hand, combines many aspects of cell activity (transport, enzymology, energy metabolism) in order to make the transcription decision. Briefly, it is impossible to show that arranging the order of the genome in any cell occurs independently from physiological or biochemical processes.

The principle of “using combinations in the arrangement of specific binding regions” is commonly used in metabolic signal networks that control cell physiology and the differentiation of cell (morphogenesis) that are oriented towards tissue formation. Such an interaction takes place on these network paths between proteins and DNA sequences to ensure that the cell is allowed to process molecular information and to calculate whether it will transcribe a specific genetic sequence. The common binding regions on DNA have vital roles in the coordinated control of various genetic loci, and it is then that the decoding of genes in a harmonious (symphonic) manner becomes possible. Various combinations of these regions are also used in making more complex decisions. As an example, protein-binding regions that are involved in the lowest level of genomic indicators have a role in decoding genes. The proteins that bind to these DNA sequences can become active when they form a group that has an interaction with more than one protein molecule. For instance, each one of the lacO and CRP regions on the lactose operon shows a palindromic sequence structure (the DNA sequence remains the same when the sequence is read from either end). Similarly, the lacP region has two lower regions that are appropriate for the binding of RNA polymerase and are separated from each other by a 16–17 base pair. In all living beings, the proteins and DNA sequences interact with each other. For example, the LacI repressor, which is in charge of controlling the lactose operon,has separate regions for not only binding the DNA region, but also for creating protein-protein binding as well as the binding of allolactose stimulator. The unique combinations of this region on the genome sequence result in a unique protein synthesis.

The genetic engineering procedures in cells

Some of the genetic engineering procedures that take place in the cells are as follows: Recombination systems (mutual material exchange) that are observed in homologous chromosomes (the chromosome pair derived from each parent), recombination specific to a particular region; separation of DNA sequences specific to those regions (fusion of gene pieces, VDJ recombination of genes as appointed in the immune system); the existence of systems that combine end points in non-homologous chromosomes (the binding of broken DNA parts, the formation of new genetic fusion, the formation of sequences that are open to hyper mutations); DNA transposons (DNA sequences that can insert themselves into different DNA sequences or can copy themselves there and leave a copy); the RNA sector that can control the transcription and signals that are responsible for the maturing transcription; the signal sequences that cause the rearrangement of neighboring DNA sequences (such as amplification, deletion, and inversion); and finally, controlling the transcription with micro RNAs.

None of the above phenomena which cause in-cell changes are random. Each of the genetic engineering functions is planned in a way that makes specific changes and arrangements. In the processes of insertion, i.e. when a specific amount of DNA is added to a different region of the genome, or deletion, i.e. when a specific amount of DNA is severed, there should be arranging, cutting and coding sequences that will bind the cut part to its new place in an appropriate way. On the genome, special regions that are suitable to mutation are created in order to produce variety and to respond to adaptation. When all these molecular engineering functions are thoroughly analyzed, it can be seen that even the point mutations, which up until now were thought to have happened by chance, are not coincidence; rather, they occur through the divinely designed genetic engineering functions. Most of the mutations that are thought to occur by chance in the cell have been removed by the repair systems and fault correction functions in the cell. Thus, the changeability and variety in DNA sequences are shaped by the power and will of God the Almighty according to a planned, programmed genetic schedule.

The R&D department of the genome

Depending on the stimulation received, God-given genetic engineering functions are arranged in the cells and a decision is made about which parts of the genome should be changed. Some of the changes inside the cell appear on a large scale. Inside the genome, different and far removed regions can be rearranged. The changes are related to one another and are in no way disconnected. One mechanism can produce more than one change. The reconstruction of changes in some organisms is a part of the normal life cycle. In the Cornelius protozoan, the embryonic genome is regularly decomposed to a thousand slices. Then, through processing and rearranging in the cells, a functional genome with a distinct system structure is created.

While the genome is reshaped, there is the production of new different sequences rather than the sequences that they regulate and which have the code for the continuity of existing phenotype features. The organization of the genome along the system base emerges with the functions of the genetic molecules, such as cut-paste-rearrange. For example, in immune system cells, there is a planned disposition to mutation and the specific antibodies are rearranged to recognize an infinite number of different antigens. The life cycles of lymphocytes demonstrates both the control of the DNA rearrangement improvements and the specificity of mutations. It is estimated that the new sequences which do not change the existing structure operate like a research center for the genome.

The God-given genetic engineering systems imposed in the cells, when analyzed from the perspective of the population, are molecular mechanisms that carry out basic changes to ensure adaptation. The duty of reconstructing the genome during adaptation has been assigned to the divine genetic engineering functions imposed in the cell. The divine genetic engineering tools and mechanisms, which are placed in the cell with active nucleic acid elements that carry information, change the genome in parallel to the changes in both the inner and outer environment; this change occurs not only on one point of the genome, but rather on every point of genome. The functions of the DNA elements, which allow for the exchange of genetic information (both horizontally and vertically, in species and between species, between types and classes), are arranged by domestic cell signal transfer and data process networks. The signal network systems that are in charge of rearranging and controlling in-cell procedures not only control when the genome is rearranged, at the same time it decides where these rearrangements take place inside the genome. The selection of the target is planned, it is not random. For instance, R1 and R2 retrotransposons which are established in the DNA region that codes 28S ribosomal RNA have specific recognition regions and the information of endonuclease cutting DNA region on specific points that it had settled down. Eukaryotic cells have more complex decision making systems. The cells continuously create responses in response to DNA damage, cell physiology and outer-cell reproduction factors. One of the critical questions and answers is whether the damage will be repaired or whether programmed death will take place. If the cell avoids giving an answer, then genetic indecisiveness appears and abnormal cell reproduction, i.e., cancer, begins. From this perspective, cancer is a result of pathology in the signal and information process in the cell. The changes in gene expression without any changes in the DNA sequence (epigenetic) as well as the divine genetic engineering functions are clear proof demonstrating that every single action in the cell occurs with a certain aim that is based on knowledge and calculations.

Hamza Aydin holds a PhD in biology.

References

• Shapiro J. A.(2001). “Genome Formatting for Computation and Function: Genome Organization and Reorganization in Evolution: Formatting for Computation and Function.” Presented at the “Contextualizing the Genome” symposium, Ghent University, Belgium, November 25–28, 2001 (Ann. N.Y. Acad. Sci., in press).
• –. (2005). “A 21st century view of evolution: genome system architecture, repetitive DNA, and natural genetic engineering.” Gene 345 (2005) pp. 91–100.
• Shapiro J. A. and Sternberg R V (2005). “Why repetitive DNA is essential to genome function.” Biol. Rev. (2005), 80, pp. 1–24. Cambridge Philosophical Society. DOI: 10.1017/S1464793104006657.

He has granted you from all that you ask Him. Were you to attempt to count God’s blessings, you could not compute them. But for sure, humankind is much prone to wrongdoing (sins and errors of judgment) and to ingratitude. (Ibrahim 14:34)

Today a large part of modern science focuses on understanding the human body. Researchers working on life sciences hope that one day the secrets of every single detail that make us human will be revealed. Every year billions of dollars are spent by scientific institutions on learning more about us. Actually this fact by itself is enough to suggest how little control we have over things happening in our bodies, and we know even less about the mechanisms of moving, touching, speaking, seeing, or hearing, and so on.

As a scientist, I really cannot guess whether life scientists will ever be able to learn enough to solve the puzzles of the human body, but I feel a lack of satisfaction when the knowledge we have gained from scientific discoveries is compared with what is unknown. In my opinion this is why one of the most intelligent physicists in history, the Nobel laureate Richard Feynman, once said, “I was born not knowing, and have only had a little time to change that here and there” [1]. My understanding is that such a conclusion must be inevitable if the primitive knowledge given to us by modern sciences is not interpreted in the light of a far superior logic that is meant to explain the whole creation. In that sense, I believe that we have to consider every single detail in creation as a vital part of the whole in order not to feel lost before the grand picture of this masterpiece.

Last year, in a seminar at Osaka University Graduate School for Frontier BioSciences, I was thrilled to hear Professor Keichi Namba say, “Japan’s fastest supercomputer dissipates more than billion times the power dissipated by a fly’s brain, yet it is not able to simulate the brain of such a tiny animal.” This worked as a wakening call or a reminder for me to think again about the magnificent arts of the Creator. In particular, I wanted to revise my research on a hearing-related protein from a new perspective, rather than using the mechanical attitude that is followed most of the time.

This article is an attempt to explain an amazing mechanism in our ears that enables us to hear the faintest whispers. A mechanism that is switched off at loud cries to protect us from disturbing noises, yet amplified to make the softest sounds audible. Before starting to explain the basic anatomy of the human ear, I should mention that today the ear’s active amplification mechanism is still being investigated in research centers by biologists and physicists together.

How do we hear? What is happening in the inner ear?

Findings from the last century have shown that our ears are not just simple receivers as we had imagined. In 1979, David Kemp of University College, London discovered that mammalian ears can also emit sound vibrations. By placing a very sensitive microphone close to the eardrum he could detect whistles, implying that there is a source of vibration within the ear [2]. However, before trying to explain the cause of vibrations in the ears, we have to go over the mechanism of hearing briefly: The delicate design of the outer ear, the tympanic membrane (eardrum), and the tiny bones (malleus, incus and stapes) enables to collect sound waves traveling in the medium and transfer them to the inner ear (Figure 1a). In the inner ear the sound waves are sorted according to their frequency and amplitudes and then converted into electrical signals which can be transported to the brain via nerves. At the onset of this process the sound waves are transformed into standing waves on the basilar membrane which is laid along the organ resembling a snail, the cochlea (Figure 1b). The frequency of the incoming sound wave determines the positions of the distortions along the cochlea: High pitches create vibrations at the basal end of the cochlea (i.e. adjacent to the middle ear) whereas low frequencies vibrate closer to the apical end (Figure 1c) where the cochlea gets narrower. This geometry helps our ears to act as a frequency analyzer.

The efferent and afferent nerves that connect the ear to the central nervous system are attached to the organ of Corti, which is situated right next to the basilar membrane, extending over the cochlea. In other words, Corti is the sense organ of hearing, converting the motion of the basilar membrane into electrical signals that are conducted to the brain via neuronal cells [3]. The organ of Corti is also lined with multiple rows of sensory hair cells.

The hair cells of the organ of Corti

Corti is decorated with two different sets of sensory cells: single row of inner hair cells (IHCs) accompanied with 3–4 rows of outer hair cells (OHCs), both spanning the whole cochlear tube (Figure 2a). They are called “hair cells” because both IHCs and OHCs have typical bundles of stereocilia that contain mechanosensitive ion channels (Figure 2b).

The major function of IHCs is to detect the sound waves and then convert them into equivalent electrical signals that are to be interpreted by the brain. When the basilar membrane is perturbed by the incoming sound waves, the IHCs found in that region sense this activity by the movement of their hair bundles (bundles of stereocilia). The hair bundles of IHCs deflect and re-align as the basilar membrane moves up and down (Figure 3). We should note that this is an amazingly sensitive process such that deflections of the stereocilia on the order of a few nanometers (one millionth of a millimeter) can be detected and converted into nerve signals by the IHCs [4].

However, this by itself is not sufficient for hearing; no matter how effective IHCs work, the fluid that fills the cochlear tube is a threat to the sound waves traveling in the inner ear. In 1948, a young astrophysicist named Thomas Gold was the first person who has pointed out that the fluidic nature of the cochlea would dampen the sound vibrations and make them too weak to be detected by IHCs. He has concluded that an inherent vibration amplification mechanism is necessary in order to overcome such a problem [5]. Unfortunately, Gold’s statements were overlooked by the physiologists of his time who had performed their hearing related experiments on dead cochleas.

Gold’s predictions were justified around ten years later by William Rhode, a physiologist from University of Wisconsin, who has shown that the vibrations of the basilar membrane in live tissue samples are stronger than anticipated [6]. In the present day the existence of an amplification mechanism within a live cochlea is a well accepted fact. The only disagreement among scientists is about how the mechanism of the amplification works. Several scientific laboratories have reported different experiments performed on the organ of Corti and they have proposed different models. At the center of one of these models is prestin, a membrane protein which is not found in any cell but OHCs in the human body.

Electro-motile outer hair cells and prestin

In 1985, the distinctive properties of OHCs were first discovered by William Brownell, a University of Geneva neuroscientist, who has shown that these cells can convert electrical signals into motion: A phenomenon called electromotility. Electromotile OHCs can elongate or shrink in response to electrical charge density changes in their membranes. About a decade ago Peter Dallos and co-workers from Northwestern University in Chicago discovered a membrane protein, unique to OHCs, that can respond to electrical signals [3]. The Dallos group coined the name “prestin” for this protein in an analogy with the musical term “presto” (quickly) due to its rapid response to electrical signals. Various kinds of mammalian cells genetically engineered to produce prestin at their membranes displayed the electromotile responses that are very similar to OHCs.

According to Peter Dallos prestin protein works as a tiny machine which is a crucial element for cochlear amplification [7]. His theory is verified by recent studies which show that cochlear sensitivity in mice decreases hundredfold when prestin activity is disrupted by genetic means [8]. As the sound waves reach the inner ear, prestin-driven electromotility enables the OHCs to move like pistons. The piston movement in phase with the basilar membrane motion amplifies the vibrations and makes them stronger for IHC detection (Figure 4a,b). The prestin-driven vibrations were what Thomas Gold proposed and David Kemp had detected so many years ago. However, scientists are still searching and learning new things about this nanometer scale machine. One of the discoveries showed that prestin can adjust itself according to the amplitude of the incoming sound waves: Basically, the amplification is stronger when the sound waves are hard to hear but gets weaker as the volume increases.

Up to this point, we have briefly explained how the amplification mechanism of hearing in mammals works. Unfortunately, even though it took decades of research for scientists to discover and define the active nature of the mammalian ear, this explanation highlights only a minuscule part of the whole picture. That is why we are still incapable of curing most hearing problems. For example, hearing loss due to slightly disturbed hair cells with damaged stereocilia turns out to be chronic (Figure 5). The medical treatments we have to hand are too primitive to mend such delicate structures. Moreover, hearing aids made by today’s technology are not nearly as effective and functional as needed.

On the other hand, the delicacy of the hair cells and the limited control scientists have over them are not the only lessons we have learned from research on the inner ear. We cannot overlook the other messages attached to the research on the grounds that the time given to us is just too short to comprehend. It is an undeniable fact that the sense of hearing is designed in the best way to serve human beings. The different characteristics of hearing amplification at different sound levels make life much easier for us: Prestin-driven hearing is most effective when the sound waves are weak and harder to hear. This way the incoming sound waves are amplified enabling us to hear the faintest whispers. However, as the sound strength increases, the prestin-driven amplification gradually gets weaker and finally diminishes after a point to make sure that loud noises are less disturbing and hazardous for us. In my opinion, this amazing quality of a tiny protein found in our ears is one of the pieces of evidence that remind us of the necessity of pondering the favors of our Creator. Qur’anic verses such as Ibrahim 34 at the beginning of this article give us clues about how to interpret scientific findings that reveal the amazing qualities of our bodily organs. May the Creator of our ears allow us to reflect more on His favors and live accordingly.

Hamdi Sener is a biophysicist living in Boston. He can be contacted at hamdisener@gmail.com.

References

1. Gleick, J., Genius: The Life and Science of Richard Feynman. Reprint ed. 1993: Vintage. 560.
2. Kemp, D.T., The evoked cochlear mechanical response and the auditory microstructure- evidence for a new element in cochlear mechanics. Scand Audiol Suppl., 1979. 9: p. 35–47.
3. Zheng, J., et al., Prestin is the motor protein of cochlear outer hair cells. Nature, 2000. 405(6783): p. 149–55.
4. Robles, L. and M.A. Ruggero, Mechanics of the mammalian cochlea. Physiol Rev., 2001. 81(3): p. 1305–52.
5. Gold, T., Hearing II. The physical basis of the action of the cochlea. Proc. Roy. Soc. B., 1948. 135: p. 492–498.
6. Rhode, W.S., Observations of the vibration of the basilar membrane in squirrel monkeys using the Mossbauer technique. J. Acoust. Soc. Am. , 1971. 49: p. 1218–1231.
7. Cho, A., What’s Shakin’ in the ear? Science, 2000. 288: p. 1954-1955.
8. Liberman, M.C., et al., Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier. Nature, 2003. 419: p. 300-304.
9. Fettiplace, R. and C.M. Hackney, The sensory and motor roles of auditory hair cells. Nat Rev Neurosci., 2006. 7(1): p. 19-29.
10. Dallos, P. and B. Fakler, Prestin, a new type of motor protein. Nat Rev Mol Cell Biol, 2002. 3(2): p. 104-11.

Cryptography mainly aims to save information and to transfer messages to recipients safely. Cryptography can change a message into a complicated form by applying several different methods. Encoded information can be resolved only when the receiver applies specific methods to it. Not only does computer cryptography render communication secure but it also gives users secure access to servers.

Nowadays, cryptography is becoming more and more significant, especially now people transfer their personal, commercial, military or political information to each other on internet. It is easy for someone to get personal information through online shopping sites which are very common today. Therefore, credit card information entered into the website is converted into unintelligible characters through an encryption method so that the credit card number can be transmitted to the server securely. Then, the server can easily retrieve the original form of the credit card number using decryption.

The encryption algorithm includes essential elements known as the “key.” Protection of the key is always vital for information security.

History of Cryptography

To find the first examples of cryptography one needs to go back more than 4,000 years in history. For instance, in 2000 BCE the ancient Egyptians used hieroglyphs on the gravestones of their kings to describe their achievements when they were alive. Eventually, the system of hieroglyphs grew too complex to understand. Then people began to use it for encoding. Similarly, Chinese people used ideography, which conveys ideas through symbols, to hide the meaning of words.

There are also encoding examples from ancient Mesopotamia that have similar aspects to those used in Egypt. The Roman emperor Julius Caesar used a type of encryption technique called the “Caesar cipher” in which each letter in the plain text is replaced by a letter some fixed number of positions down the alphabet. In the Middle Ages cryptography received a lot of attention from many nations, especially in Europe. In recent years, many different methods have been developed in this field. Therefore, the classical methods are not as useful as they were in the past, especially since the 1970s. Today, more complex mathematical methods have replaced the classical methods of cryptography.

The Arabs were the first to make successful studies of how to decode encrypted messages. Ahmad al-Qalqashandi of Egypt (1355–1418) developed an encryption method which is still used today. This technique is based on a theory of language stability which explores the distribution and frequency of the words in a text. With this method, the frequency of the characters within the encrypted text is compared to the frequency standards in the language; in this way, it is determined what an encoded letter really stands for.

This method is used successfully in decoding messages encrypted by the mono-alphabetic method, which is based on sliding or replacement of a letter by another one.

In 1931, the French obtained documents from a German spy which showed the functions of a code named “Enigma” that was going to be used in World War II by the Germans. British mathematicians were then able to decipher the code during the war. Thus, the commands of Hitler could be learned immediately by the Allied Powers. The Allied countries won the war because of their access to the decryption technique. Likewise, the American army gained victory over the Japanese in the Pacific War in the 1940s because American decryption experts, along with their British and Dutch colleagues, were able to decode the system called JN-25 which was being used by the Japanese army.

Technological developments in computer science have enabled us to decode even previously unbreakable ciphers. For instance, an encrypted message which was created in 1977 and which, it was thought could be decoded only 40 quadrillion years later with the help of an algorithm that analyses the known large numbers into their factors, was actually decoded seventeen years later in 1994.

Classical and modern cryptography

Cryptographic methods are divided into two categories: classical and modern. In the classical method, encoding can be done by consistent replacement of a letter by another letter in the same alphabet. For example, if we replace each letter in the word FOUNTAIN by the third following letter it changes into IRXQWDLQ. It can also be done by replacement of a word with another one or replacement of a character by another character. Of course, the recipient of the message must be the only person who knows the decryption method. In that way, for example, the unintelligible word above can easily be changed back to its original form by replacing each word by the letter three places before it in the alphabet. Such encrypted messages can only be decoded by linguistic analyses or after numerous trials. The classical method was invented hundred of years ago, and it has been used since then. Although this method is so simple that it can even be used manually, computers are the only devices which can have maximum security as well as very long keys and complex algorithms for the modern technique.

The “Spartan cylinder” is another device used in the classical method. A message is written on a piece of paper rolled around a cylinder with a known diameter. The encrypted message is then detached from the cylinder and sent. The only way to decipher the message is to have a cylinder of the same diameter. If the unrolled paper is re-rolled around a decoding cylinder properly, then the original message is obtained. This method is known to have been used by the Spartans around 600 BCE.

One modern method is called Public-Key Cryptography. In this form of cryptography, the key used to encrypt a message differs from the key used to decrypt it. The public key may be widely distributed while the private key is kept secret. Thus, incoming messages are encrypted with the recipient’s public key; yet, they cannot be decrypted except with the recipient’s private key. Hence, the possessor of the private key is the only one who can decrypt the message and read it.

Conversely, in secret-key cryptography, a single secret key is used for both encryption and decryption. One disadvantage of secret-key cryptography is the distribution of the private key since it is always at risk of being acquired by third parties.

If we look at the universe, we can observe similar cryptographic methods in every creation process. For instance, living cells produce protein by deciphering nucleic acids (DNA, RNA), which include encoded genetic information in ribosomes.

The structure of encoded DNA and encryption in protein synthesis

There is divine wisdom in the encoding of DNA and the transference of these codes to ribosomes in the protein-making process. If we compare DNA molecules, which contain the genetic instructions inside living organisms, to a book, the letters in this book can be symbolized by A, T, and G and C. These symbols represent four molecules which are used in the encoding of the genetic program that shapes the basic form of all living organisms. Each human genome is identified with different sums of those letters. For instance, while the sum of genomic letters is approximately 3 billion in mice and human organisms; it is about 4–5 million in a bacteria. Furthermore, when the genome sequences of two humans are compared, the combination difference between the two appears to be only one percent; nevertheless, no human being is exactly like another in appearance.

There are some interesting distinctions between humans and animals in terms of their genome numbers. The various encoding techniques used in DNA are a basic biological mechanism which can also be considered the mystery behind the genetic diversity in the creation of living organisms. If we compare the genome to a program booklet, we can consider the booklet to be a tiny model of the “Manifest Record” (Imam al-Mubin) mentioned in the Qur’an, in which the future lives of all things and beings, including all the principles governing those lives, and all their deeds and the reasons or causes are kept pre-recorded in this world. The instructions and mechanism used in this encoding program are identical in most living beings. This uniformity shows that they are all created by one Almighty being.

Scientists also observe another kind of encoding which helps transmission of the right message to ribosomes during the protein-making process. The main idea is that unlike the base-pairing of DNA, in messenger RNA (mRNA) the complementary base to adenine is not thymine, as it is in DNA, but rather Uracil, and also that every three nucleotides (a codon) carry information of one amino acid. For example, while codons in DNA appear as “AAT, GCC, GAT, GTA,” they appear as “UUA, CGG, CUA, CAU” in mRNA. Here the main goal is not to keep the information safe against the third parties as in normal encryption, but rather to transmit the message properly and preserve the diversity of living beings.

Developments in the area of cryptography do not only provide confidentiality of information, but they also shed light on our understanding of God’s wonderful creation in the world of living creatures. All these extensive and essential practices, including the encoding of the information by the four letters of DNA, proper transmission of this encoded information to the cells, and the necessary synthesis in the cell, prove that the All-Knowing and Omnipotent God has great wisdom in all His actions in the Universe.

References

• Protein Synthesis, http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookPROTSYn.html.
• Selim Aydın, “Gen Haritası Neler Söylüyor?”, Sızıntı, June 2001, no. 269.
• Quantum Cryptography: Privacy Through Uncertainty, October 2002 http://www.csa.com/discoveryguides/crypt/overview.php 1.5.2006.
• Larry Petterson, Bruce S. Davie, Computer Networks: A System Approach, Morgan Kaufmann Publishers, 2000, 568–615.

And surely in the cattle (feeding on the pastures of the revived earth) there is a lesson for you: We give you from that which is within their bodies, (marvelously distinguished from) between the waste and blood, milk that is pure and palatable to those who drink. (Nahl 16:66)

Ruminants, probably the most abundant of the herbivores such as cattle, sheep and goats, are foregut fermenters with a four-chambered stomach (rumen, reticulum, omasum and abomasum) and are an essential component of utilizing marginal land in the world in a sustainable way.

In the verse above from the Qur’an, the Creator and the Sustainer of the universe draws our attention to many of the benefits we get from domestic animals. While the main message of the verse is easily understandable to the general reader, it also contains some concise hints, even descriptions about the physiological details of milk production in ruminants that would be fully understood and explained by science only centuries after the Qur’an was revealed. The purpose of this article is to explain this process in a general sense and milk production in some detail.

Mammals are generally categorized according to the dietary habits into three classes-flesh-eating (carnivore), plant-eating (herbivore) and both flesh and plant-eating (omnivore). In a sense, humans (omnivores) and carnivores depend on herbivores for their nutrition. Generally speaking, all humans and animals in the world have directly or indirectly benefited from the plants. The ability of herbivores to utilize plants as their main energy source is dependent on symbiotic microorganisms which live at various sites within their gastrointestinal tract. The animal provides the microorganisms with food and habitat for growth and the microorganisms provide the animal with fermentation acids and microbial protein.

Herbivores are divided into two types, those with post-gastric (hindgut) fermentation and those with pre-gastric (foregut) fermentation. Fermentation is a chemical process during which microorganisms obtain energy from organic products. Ruminants, probably the most abundant of the herbivores such as cattle, sheep and goats, are foregut fermenters with a four-chambered stomach (rumen, reticulum, omasum and abomasum) and are an essential component of utilizing marginal land in the world in a sustainable way. Rumen and reticulum contain millions of microorganisms, which form about 3 to 10 percent of rumen fluid.

A major reason why human beings keep ruminants is their ability to convert food which humans find inedible-or at least unpalatable-to food (meat, milk) which humans can eat. They play an important role in the livelihood of farmers throughout the world, providing sustenance such as milk and meat, manure for crop production, cash income from sales of their products and a safety net of capital assets to face risks and misfortune in harsh environments. Currently, humans obtain about fifty percent of the meat and most of the milk they consume from ruminants. Scientists who have conducted studied on ruminants have developed cow breeds, which have higher milk and meat production than traditional cow breeds, and thus supplied an important development to meet the nutritional requirements of humans.

Pre-gastric fermentation provides three important nutritional advantages to the host animal.

First, cellulose and other plant polysaccharides are brought into solution and become available as energy sources. Cellulose is the most abundant natural carbohydrate polymer in nature, but mammals do not produce enzymes that can degrade it. Ruminant animals utilize cellulose via a symbiotic relationship with ruminal cellulolytic microorganisms. During ruminal fermentation, microorganisms ferment the carbohydrates to produce energy, gases (methane and carbon dioxide), heat, and volatile fatty acids (VFA) in the rumen. Effective digestion of plants requires a means of dealing with cellulose, the most important structural material of plants, which is extremely insoluble and remarkably resistant to a chemical attack. Cellulose digesting enzymes that are called cellulases and produced by microorganisms are also present in the intestinal tract of several invertebrates that feed on wood and similar plant products. Rumen harbors the different functional groups of the microbial population, which is responsible for about seventy percent of total digestion in ruminants, and the ability to digest cellulose has been ascribed to a large number of bacterial, fungal and protozoal species isolated from the rumen.

The energy content of plants is low, and the herbivore must consume a large quantity in order to satisfy its energy requirements. Therefore, herbivores spend a lot of time eating; eight or more hours per day may be spent eating.

Secondly, the rumen microorganisms can utilize non-protein nitrogen for growth, converting it into microbial protein which becomes available to the host. Proteins provide the amino acids needed for maintenance of vital functions, reproduction, growth and lactation. Non-ruminant animals need pre-formed amino acids in their diets, but ruminants can utilize many other nitrogen sources because of their rare ability to synthesize amino acids and protein from non-protein nitrogen sources via a symbiotic relationship with ruminal microflora.

Ruminants possess a rumeno-hepatic nitrogen circulation mechanism, which does not exist in non-ruminant animals, in order to save nitrogen. By this mechanism, ruminants can be fed non-protein nitrogen sources such as urea and nitrate when nutrients are in short supply to obtain high quality milk protein. Feed proteins are degraded by microorganisms in the rumen via amino acids into ammonia. Ammonia is used by bacteria to build their proteins and any excess of it is absorbed through the rumen wall into the blood and then converted to urea in the liver. When a diet is low in nitrogen, large amounts of urea (which is normally excreted in the urine) return to the rumen where it can be used by the microbes. In non-ruminants, urea is always entirely lost in the urine. If ammonia levels in the rumen are too low there will be a nitrogen shortage for bacteria and feed digestibility will be reduced. Too much ammonia in the rumen leads to wastage, ammonia toxicity, and in extreme cases, death of the animal.

Thirdly, vitamin synthesis by the microbial population makes the ruminant animal virtually independent of dietary sources of all vitamins, except for vitamins A and D.

However, rumen fermentation also brings some disadvantages. First of all, rumen metabolism causes environmental pollution. Methane is produced as a natural consequence of the anaerobic fermentation; it is a potent greenhouse gas. Dairy farming is the largest agricultural source of methane, one of the greenhouse gases. Furthermore, the major environmental concern associated with the animal industry is ammonia volatilization, which increases atmospheric acid deposition because of the impact of nitrogen-rich excreta on the environment. Therefore, worldwide, scientific research projects have been carried out to find sustainable strategies for reducing emissions of the greenhouse gas methane and ammonia volatilization from domestic ruminants to the environment.

In conclusion, the symbiotic relationship between ruminants and ruminal microorganisms plays an important role in the recycling of nutrients between humans and plants. This relationship also contributes to human life by converting low quality nutrients (grass and hay) to high quality food (meat and milk). Humans will benefit more from ruminants as scientific knowledge about relationships between ruminants and rumen microorganisms advances.

Zubeyir Altuntas has a PhD in Molecular Medicine. He is a research associate in Immunology Department of The Cleveland Clinic.