Basal ganglia subcircuits distinctively encode the parsing and concatenation of action sequences.
Jin et al. Nature Neuroscience, Jan 2014.

When we learn to play a musical instrument – say the guitar – first, we have to learn notes, scales and chords; only then we will be able to play a song. The very same rule applies to our basic functions. For example, when we learn how to read, we first learn the alphabet and the rules of grammar, and then we start making sense of sentences. Neuroscientists have been intrigued by this process for many years and they have wanted to understand how our brains efficiently perform complex cognitive functions by connecting separate elements to produce a unique meaningful sequence. A recent study shed some light on this very important question. Scientists found that a specific area of the brain, the basal ganglia, can signal the integration of individual elements into a behavioral sequence. Scientists designed an experiment where they first trained mice to perform gradually faster sequences of lever presses. This behavioral test is very similar to a person learning to play a guitar solo at an increasingly faster pace. Then, they recorded the neural activity in the basal ganglia of mice performing the task and discovered that basal ganglia neurons treat a whole sequence of actions as a single behavior. This mechanism is called “chunking,” which allows the brain to efficiently organize memories and actions by integrating individual sequences. It seems like the basal ganglia implement the “chunking.” The basal ganglia are known to include two major pathways, the direct and the indirect. Scientists found that these two pathways show similar activities during the initiation of movement, but show differential activations during the execution of behavioral sequences. Interestingly, basal ganglia circuits are implicated in Parkinson’s and Huntington’s disorders, in which learning of sequences are compromised. Further studies will reveal a more mechanistic understanding of sequence integration in the brain and potential interventions to enhance it in neurological disorders.

Single Gene Separates Queen from Workers

Ubx promotes corbicular development in Apis mellifera
Medved V. et al. Biology Letters, Jan 2014

In a hive of honey bees, the queen and worker bees have very different jobs. A new study shows that a single gene called Ultrbithrox (Ubx) separates a queen from worker bees. The Ubx gene was previously known to control leg and hindquarter development in bees. Interestingly, researchers now identified three functions for Ubx specific to worker bees. First, Ubx promotes the development of a smooth spot on the hind legs where the “pollen baskets” are located. Second, Ubx directs the formation of eleven perfectly spaced bristles on the section of the leg called the “pollen comb.” Third, Ubx mediates the formation of the “pollen press” which is a protrusion that helps pack and transport pollen back to the hive. Essentially, the Ubx gene promotes the development of three different physical structures on worker bees so that they can collect and transport pollen. Researchers confirmed these findings by silencing the Ubx gene genetically in worker bees and found that specialized leg features, including pollen combs and pollen presses, completely disappeared in the absence of the Ubx gene. Moreover, analyses of other bee species in the region revealed that the size and complexity of pollen baskets are directly correlated with the social behaviors of the particular bee species, suggesting that pollen baskets have yet-to-be-identified roles on the social behaviors of bees. Furthermore, the pollination of 35 percent of the world’s crops (with a $216 billion market value) depends on bees carrying pollen from one flower to another. This study might help us to develop new genetic approaches to make bees better, more efficient pollinators and to ultimately combat the worldwide pollination problem.

Molecular Switch in Aging Blood Cells Discovered

A canonical to non-canonical Wnt signaling switch in haematopoietic stem-cell ageing
Florian MC et al. Nature, October2013

Every single cell in our body ages over time. The aging of a cell is typically characterized by the progressive loss of physiological function and increased vulnerability to death. The aging of our cells/tissues/organs is the primary risk factor for any human diseases. One critical cell type that dramatically changes its properties during aging are blood stem cells, aka Hematopoietic Stem Cells (HSCs). Young HSCs have the capacity to differentiate into the diverse lineages of erythroid, lymphoid, and myeloid cells. Young HSCs are polarized (asymmetrical) cells, in which distinct cytoskeletal proteins (also called the “polarity complex”) are asymmetrically distributed within. However, the aged HSCs are mostly apolarized (symmetrical) cells and they differentiate only into lineages of myeloid cells (including, red blood cells, macrophages and monocytes) rather than lymphocytes (white blood cells in the immune system). The molecular changes in aging HSCs have largely been unknown. A recent study published in Nature shed some light onto the molecular identity of the ageing HSCs. Scientists showed that ageing HSCs have higher levels of a secreted protein called WNT5a, whereas the young HSCs have almost no WNT5a protein expressed in the cell. Moreover, the increased levels of WNT5a are found to attenuate the levels of the “polarity complex” proteins in HSCs and thus result in apolarized cells, which resemble the aging HSCs. Furthermore, transplantation studies revealed that increased WNT5a levels cause aging-related phenotypes and low Wnt5a levels promote a rejuvenation process in mice. These findings show that Wnt5a is the key molecule that controls the shift between young and old HSCs. Therapeutic approaches using antagonists of the Wnt5a molecule could potentially alleviate aging-related pathologies in the patients with a variety of blood diseases.

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.

These findings might help researchers to design more effective drugs for various human infections by focusing on the minimization of the inflammation. Moreover, bats are capable of sustained long flights, as some bat species can fly more than 1,000 km in a single night. With such intense physical activity, cells often produce high levels of toxic (free radicals) that would usually damage DNA sequence.

This study also found that bats are equipped with a highly functional set of genes that mediates DNA repair in response to DNA damage, thus bats are protected from toxic cellular waste with this advanced mechanism. Aging, cancer and infectious diseases are the three major issues medicine is facing today and biological abilities granted to bats seem to provide important clues for us to discover new ways to combat these big health problems

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.

At the end of the 1950s, Richard Feynman (1961, pp.282-96) described the possibility of building computers that were ‘sub-microscopic’. More recently, several people have advocated the realization of massively parallel computation using the techniques and chemistry of molecular biology.

At the end of 1994 Leonard Adleman published a paper on ‘Molecular Computation of Solutions of Combinatorial Problems’ (Science, vol.266, pp.1021 – 24). He explained how a problem could be set up by synthesizing DNA molecules with a particular sequence, and solved by letting the DNA molecules react in a test tube, producing a molecule whose sequence is the answer. In the same paper he recounted how he had put this theory into practice by solving a standard problem with a DNA reaction system. Adleman called his DNA computer the TT-100, for test tube filled with 100 microlitres of fluid, which is all it took for the reactions to occur.

Since then, many advances have been proposed to refine the protocol for programming a DNA computer to reduce the complexity of the operations and eliminate errors (see Lipton, n.d.; and Boneh and Lipton, nd.). Despite their respective complexities, biological and mathematical operations have some similarities:

The very complex structure of a living being is the result of applying simple operations to initial information encoded in a DNA sequence.

The result f(w) of applying a computable function to an argument can be obtained by applying a combination of basic simple functions to w.

For the same reasons that DNA was probably selected for living organisms as a genetic material, its stability and predictability in reactions, DNA strings can also be used to encode information for mathematical systems.

Conventional computers represent information in terms of 0’s and l’s, physically expressed in terms of the flow of electrons through logical circuits. Builders of DNA computers represent information in terms of the chemical units of DNA. Calculating with an ordinary computer is done with a program that instructs electrons to travel on particular paths; with a DNA computer, calculation requires synthesizing particular sequences of DNA and letting them react in a test tube. In a scheme devised by Lipton (n.d.), the logical command AND is performed by separating DNA strands according to their sequences, and the command OR is done by pouring together DNA solutions containing specific sequences.

‘It will fill a bathtub, not the universe,’ says Lipton, ‘and it will be incredibly cheap to build.’ A pound of DNA in 1,000 quarts of fluid, about three-feet square, will hold more memory than all the computers ever made. The chemicals are inexpensive; DNA runs virtually on its own power, and the soup, with a little splicing, can be re-used from one experiment to the next. Lipton estimates that a superparallel DNA computer, offering trillions of processors working simultaneously, could be built for $100,000.

The fastest supercomputers can currently perform 1000 million instructions per second (MIPS); a single DNA molecule requires approximately 1000 seconds to perform an instruction (.001 MIPS). Obviously, if you want to perform one calculation at a time (serial logic), DNA computers are not a viable option. However, if one wanted to perform many calculations simultaneously (parallel logic), a computer such as the one described above can easily perform 1014 MIPS. DNA computers also require less energy and space. While existing supercomputers operate 109 operations per joule, a DNA computer could perform 2 x 1019 operations per joule (many times more efficient). Data can be stored on DNA at a density of approximately 1 bit per cubic nm, while existing storage media require 1012 cubic nm to store 1 bit (Adleman, 1995).

Thus, the potential of molecular computation is impressive. However, it is too early for either great optimism or great pessimism. It is possible that DNA computers will become more common for solving very complex problems and DNA computers may also become automated. In addition to the direct benefits of using DNA computers for performing complex computations, some of the operations of DNA computers already have (Adleman, 1995), and more could be, used in molecular and biochemical research.

References

• Adleman,L.(1994).’Moleculer computation of solutions to combinatorial problems’,Science,vol.266,pp.1021-24.
• Adleman,L.(1995 ‘On constructing a moleculer computer’:ftp://usc.edu/pub/csinfo/papers/adleman/molecular_coputer.ps
• Boneh,D.&Lipton,R.J.’Making DNA computers error resitant’.(Unpublished manuscript.)
• Feynman,R.P. (1961)’Minaturization’,in D.H.Gilbert (ed.)Reinhold,New York.
• Lipton,R.J.(n.d.)’Speeding up computations via molecular biology’:ftp://ftp.cs.princeton.edu/pub/people/rjl/bio.ps

Because of their biochemical importance, the nucleic acids receive much more attention than the others. DNA was first isolated in 1869 by F. Miescher from cell nuclei. Nearly 80 years of research have been carried out to identify the major building block units and the basic structure of nucleic acids. DNA molecules from different cells and viruses vary in ratio of the four major types of nucleotide monomers, in their nucleotide sequence, and in their molecular weight. Four major bases (adenine, guanine, thiamine, and cytosine) are found in all DNA. The DNA isolated from different organisms and viruses normally has two strands in complementary double-helical arrangement, and it is the basic compound of genetic material (chromosomes). In its double-helical structure it has a 20 A (1 A=10-8 cm) diameter width and the nucleotides are repeated in every 3.4 A.

This polymeric molecule, DNA, is the chemical basis of heredity and is organized into genes, the fundamental units of genetic information. It was first demonstrated in 1944 in a series of experiments that genetic determination of the character (type) of the capsule of a specific pneumococcus could be transmitted to another of a distinctly different capsular type by introducing purified DNA from the former coccus into the latter. This agent (later shown to be DNA) was called ‘transforming factor’. Subsequently ,this type of genetic manipulation has become commonplace. Similar experiments have recently been performed utilizing yeast, cultured mammalian cells, and insects and rodents as recipients, and cloned DNA as the donor of genetic information.

DNA has the ability to replicate itself. It is this property that holds the genetic material in the same type and number sequence during the cell divisions. In prokaryotic cells, which contain only a single chromosome, essentially all the DNA is present as a single double-helical, two-stranded macromolecule exceeding 2 x 10- 9 in molecular weight. In eukaryotic cells, which contain either several or many chromosomes, there ate either several or many DNA molecules. 

The double-stranded structure of DNA can he melted in solution by increasing the temperature or decreasing the salt concentration. The denaturation of DNA is used to analyze its structure. Not only do the two stacks of bases pull apart but the bases themselves unstack while still connected in the polymer by phosphodiester backbone.

Careful examination of the model reveals a major groove and a minor groove winding along the molecule parallel to the phosphodiester backbone. In these grooves,proteins can interact specifically with exposed atoms of the nucleotides (usually H bonds) and thereby recognize and hind to specific nucleotide sequences without disrupting the base pairing of the double-helical DNA molecule. As easily seen, regulatory proteins can control the expression of specific genes via such interactions.

The genetic information stored in the nucleotide sequences of DNA serves two purposes. It is the source of information for the synthesis of all proteins of the cell and organism, and it provides the information inherited. Both these functions require that the DNA molecule serve as template – in the first case for the transcription of the information into RNA and in the second ease for the replication of the information into daughter DNA molecules.

DNA is likely to survive for millions of years in some conditions. Amber can provide some of the right conditions to preserve DNA. The most reliable report of DNA to date from amber is that of termite-like sequences from around 30 million year-old Dominican amber. The earlier recovery of DNA from a 20 million year-old magnolia leaf, near Moscow, was more remarkable because the leaf was preserved in a sequence of easily split soft clays and silts, interbedded with layers of volcanic ash.

Recent developments in genetics are providing very powerful new techniques for the analysis of DNA from remains of ancient organisms. The young field of ancient DNA research is less than a decade old but is growing exponentially. In spite of some serious technical difficulties, the study of ancient DNA promises to become a revolutionary research tool in archaeology; anthropology and molecular biology.The earliest report of retrieval of informative DNA sequences from extinct animals – in this case from the desiccated skin of a quagga, a member of the horse family which became extinct more than one hundred years ago – was that by A. Wilson and his colleagues in 1984. Shortly after this, DNA was isolated by S. Pbo from the skin of a pre-dynastic Egyptian mummy; it was shown by DNA hybridization that a small amount of recognizable human DNA was left in the ancient tissue. In 1988, the first report of an amplified ancient DNA sequence was made by S. Pbo and colleagues who retrieved it from a 7,000 year-old skull found in a peat bog.

It seems likely that studies of this kind will become even more popular in the near future. With the ancient DNA sequence studies, one of the most controversial problems in biology – evolution – will possibly be enlightened. No there is a drive to gather genetic information from indigenous groups to increase our understanding of human origins, history and migrations. Ancient DNA studies will play a very important role by providing a direct source of objective evidence on past populations, and perhaps the only reliable insight into the genetic characteristics of vanished peoples.