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	<title>transcription &#8211; Fountain Magazine</title>
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		<title>Recurring DNA in Genome Structure</title>
		<link>https://fountainmagazine.com/all-issues/2013/issue-93-may-june-2013/recurring-dna-in-genome-structure-may-2013/</link>
		
		<dc:creator><![CDATA[Louima Cunningham]]></dc:creator>
		<pubDate>Wed, 01 May 2013 00:00:00 +0000</pubDate>
				<category><![CDATA[Issue 93 (May - June 2013)]]></category>
		<category><![CDATA[cells]]></category>
		<category><![CDATA[cellular]]></category>
		<category><![CDATA[data]]></category>
		<category><![CDATA[dna]]></category>
		<category><![CDATA[functions]]></category>
		<category><![CDATA[genome]]></category>
		<category><![CDATA[genomic]]></category>
		<category><![CDATA[heterochromatin]]></category>
		<category><![CDATA[information]]></category>
		<category><![CDATA[organisms]]></category>
		<category><![CDATA[protein]]></category>
		<category><![CDATA[regions]]></category>
		<category><![CDATA[repeated]]></category>
		<category><![CDATA[repeating]]></category>
		<category><![CDATA[rna]]></category>
		<category><![CDATA[Science]]></category>
		<category><![CDATA[sequences]]></category>
		<category><![CDATA[structure]]></category>
		<category><![CDATA[structures]]></category>
		<category><![CDATA[system]]></category>
		<category><![CDATA[transcription]]></category>
		<guid isPermaLink="false">http://107.21.79.195/all-issues/2013/issue-93-may-june-2013/recurring-dna-in-genome-structure-may-2013/</guid>

					<description><![CDATA[A genome is a data book or registry which records the past and future of living organisms. It dynamically and simultaneously stores hereditary and biological information in three different hierarchical levels belonging to three different time periods. The first is the preservation of characteristic, long term data imprints that describes the development of an organism [&#8230;]]]></description>
										<content:encoded><![CDATA[<p>A genome is a data book or registry which records the past and future of living organisms. It dynamically and simultaneously stores hereditary and biological information in three different hierarchical levels belonging to three different time periods.</p>
<p>The first is the preservation of characteristic, long term data imprints that describes the development of an organism in the stable DNA sequences.</p>
<p>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).</p>
<p>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.</p>
<p><span id="more-1494"></span></p>
<p>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.</p>
<p>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.</p>
<ol style="list-style-type: lower-alpha;">
<li>A copy of genome is produced by cellular DNA replication system</li>
<li>Correct localization of each genome copy towards daughter cells is only possible when chromosome segregation system works (the centrosomes and microtubules)</li>
<li>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.</li>
</ol>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p>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).</p>
<p>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.</p>
<h3>Sequences encoding different information in DNA</h3>
<p>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:</p>
<ol>
<li>Group determining sequences that enable coordinated or successive expression of genes,</li>
<li>Sequences acting as a marker in charge of initiation and termination during transcription of DNA to RNA ,</li>
<li>Signal sequences responsible for conversion of primary immature RNA, sequences into smaller functional RNA molecules,</li>
<li>Transcription control sequences that determine the expression frequency of genes,</li>
<li>Sequences that identify and mark the initiation regions for intensification and remodeling of chromatins,</li>
<li>Sequences that make binding regions which affect the relocation of genome in nucleus or nucleolus,</li>
<li>Sequences that target regions where covalent DNA modification (methylation) with functional groups like methyl takes place,</li>
<li>Sequences that control and identify the regions responsible for initiation of DNA replication,</li>
<li>Sequences that make the structures which enable completion of replication at terminal ends,</li>
<li>Sequences at the segregation points that enable equal distribution of copied DNA molecules into daughter cells and centromere sequences,</li>
<li>Sequences responsible for guidance during repair of DNA bound errors and damages,</li>
<li>Start point sequences used for repackaging of genomes,</li>
</ol>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<h3><b>References</b></h3>
<ul>
<li>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 &#8220;Contextualizing the Genome,&#8221; Ghent University, Belgium, November 25 &#8211; 28, 2001 (Ann. N.Y. Acad. Sci., in press)</li>
<li>Shapiro, J.A. 2005. “A 21st century view of evolution: genome system architecture, repetitive DNA, and natural genetic engineering.” Gene 345, pp: 91–100.</li>
<li>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.</li>
</ul>
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			</item>
		<item>
		<title>Functional Art in the Nucleus: DNA</title>
		<link>https://fountainmagazine.com/all-issues/2011/issue-82-july-august-2011/functional-art-in-the-nucleus-dna/</link>
		
		<dc:creator><![CDATA[Louima Cunningham]]></dc:creator>
		<pubDate>Fri, 01 Jul 2011 00:00:00 +0000</pubDate>
				<category><![CDATA[Issue 82 (July - August 2011)]]></category>
		<category><![CDATA[cell]]></category>
		<category><![CDATA[dna]]></category>
		<category><![CDATA[double]]></category>
		<category><![CDATA[factory]]></category>
		<category><![CDATA[functions]]></category>
		<category><![CDATA[gene]]></category>
		<category><![CDATA[genes]]></category>
		<category><![CDATA[information]]></category>
		<category><![CDATA[nucleotides]]></category>
		<category><![CDATA[nucleus]]></category>
		<category><![CDATA[produce]]></category>
		<category><![CDATA[protein]]></category>
		<category><![CDATA[proteins]]></category>
		<category><![CDATA[read]]></category>
		<category><![CDATA[region]]></category>
		<category><![CDATA[regions]]></category>
		<category><![CDATA[Science]]></category>
		<category><![CDATA[single]]></category>
		<category><![CDATA[specific]]></category>
		<category><![CDATA[structure]]></category>
		<category><![CDATA[sugar]]></category>
		<category><![CDATA[transcription]]></category>
		<guid isPermaLink="false">http://107.21.79.195/all-issues/2011/issue-82-july-august-2011/functional-art-in-the-nucleus-dna/</guid>

					<description><![CDATA[Volumes of books and hundreds of articles have been published about the structure and functions of DNA, since the day two renowned scientists from Cold Spring Harbor laboratories, who would later win the Nobel Prize, described the double helix structure of it. Perhaps one common element that shines through all the publications is their emphasis [&#8230;]]]></description>
										<content:encoded><![CDATA[<p>Volumes of books and hundreds of articles have been published about the structure and functions of DNA, since the day two renowned scientists from Cold Spring Harbor laboratories, who would later win the Nobel Prize, described the double helix structure of it. Perhaps one common element that shines through all the publications is their emphasis on the numerous specific functions of DNA, if not the fascinating harmony of these specific functions in a living organism. In this article, we will take a look at a few small droplets from the vast ocean of information about the multi-layered functions of DNA that are orchestrated in an awe-inspiring manner.</p>
<p>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.</p>
<p>“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.</p>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p>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?</p>
<p>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.</p>
<h3>Different layers of complexity and organization related to DNA</h3>
<p>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.</p>
<p>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?</p>
<h3><b>References</b></h3>
<p>1. Calladine, C. R. et al. 2004. Understanding DNA: The Molecule and How It Works, Academic Press</p>
<p>2. http://www.genome.gov</p>
<p>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.</p>
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		<title>Dynamic Programs in Cells</title>
		<link>https://fountainmagazine.com/all-issues/2009/issue-72-november-december-2009/dynamic-programs-in-cells/</link>
		
		<dc:creator><![CDATA[Louima Cunningham]]></dc:creator>
		<pubDate>Sun, 01 Nov 2009 00:00:00 +0000</pubDate>
				<category><![CDATA[Issue 72 (November - December 2009)]]></category>
		<category><![CDATA[binding]]></category>
		<category><![CDATA[cell]]></category>
		<category><![CDATA[cells]]></category>
		<category><![CDATA[control]]></category>
		<category><![CDATA[dna]]></category>
		<category><![CDATA[engineering]]></category>
		<category><![CDATA[functions]]></category>
		<category><![CDATA[genetic]]></category>
		<category><![CDATA[genome]]></category>
		<category><![CDATA[glucose]]></category>
		<category><![CDATA[information]]></category>
		<category><![CDATA[lactose]]></category>
		<category><![CDATA[operon]]></category>
		<category><![CDATA[protein]]></category>
		<category><![CDATA[region]]></category>
		<category><![CDATA[regions]]></category>
		<category><![CDATA[Science]]></category>
		<category><![CDATA[sequences]]></category>
		<category><![CDATA[specific]]></category>
		<category><![CDATA[system]]></category>
		<category><![CDATA[transcription]]></category>
		<guid isPermaLink="false">http://107.21.79.195/all-issues/2009/issue-72-november-december-2009/dynamic-programs-in-cells/</guid>

					<description><![CDATA[The molecular and genetic diversity in the environmental adaptation mechanisms found in the cells of living beings establishes the ground for fundamental changes in our knowledge about the cell and the sustainability of life. Scientists are astonished by the replication and regulation of genomes in accordance with requirements, particularly the careful placement of active genetic [&#8230;]]]></description>
										<content:encoded><![CDATA[<p>The molecular and genetic diversity in the environmental adaptation mechanisms found in the cells of living beings establishes the ground for fundamental changes in our knowledge about the cell and the sustainability of life. Scientists are astonished by the replication and regulation of genomes in accordance with requirements, particularly the careful placement of active genetic elements in different genetic loci (the specific location on the chromosome) and the coordinated control of the same. That in-cell signal networks are administered during the reconstruction of the genome chain to enable responses to the necessities of adaptation, as if the cell had a mind, has been demonstrated. Since the system that regulates transcription, i.e. the transfer of coded information from the DNA to the RNA, is equipped with the ability to reach the appropriate loci of the genome at the right time, in the right place, and in the right measure, the genetic information can be decoded in a proper way. In addition, the transcription control system plays a role in both the specific directing and random binding of the active genetic elements to their genome region. Increasing the variety of genetic information in this way leads to the production of new genetic information.</p>
<h3><b>Decisions within the cell: mathematical and algorithmic character</b></h3>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<h3><b>The genetic engineering procedures in cells</b></h3>
<p>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.</p>
<p>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.</p>
<h3><b>The R&amp;D department of the genome </b></h3>
<p>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.</p>
<p>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.</p>
<p>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.</p>
<p><em>Hamza Aydin holds a PhD in biology.</em></p>
<h3><b>References</b></h3>
<ul>
<li>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).</li>
<li>&#8211;. (2005). “A 21st century view of evolution: genome system architecture, repetitive DNA, and natural genetic engineering.” Gene 345 (2005) pp. 91–100.</li>
<li>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.</li>
</ul>
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