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Defending the Christian Worlview, Creationism, and Intelligent Design

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Defending the Christian Worlview, Creationism, and Intelligent Design » Origin of life » Non random mutations : How life changes itself: the Read-Write (RW) genome

Non random mutations : How life changes itself: the Read-Write (RW) genome

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Non random mutations : How life changes itself: the Read-Write (RW) genome 2 3

A lot of E. coli suffered glucose deprivation. When the dust settled, this is what emerged. Mutations are not random: that part is correct. Bacteria have mutational hotspots – specific genes that mutate up to hundreds of thousands of times faster than average.
Paul Davies, the demon in the machine, page 78

Starving bacteria, Rosenberg discovered, can switch from a high-fidelity repair process to a sloppy one. Doing so creates a trail of damage either side of the break, out as far as 60,000 bases or more: an island of selfinflicted
vandalism. Rosenberg then identified the genes for organizing and controlling this process. It turns out they are very ancient; evidently, deliberately botching DNA repair is a basic survival mechanism stretching back into the mists of biological history. By generating cohorts of mutants in this manner, the colony of bacteria improves its chances that at least one daughter cell will accidentally hit on the right solution. Natural selection does the rest. In effect, the stressed bacteria engineer their own high-speed evolution by generating genomic diversity on the fly.

And all available scientific evidence also indicates that evolution is an engineered process. In engineering and computer science, evolution never happens by accident. It’s always the result of a deliberate act. A program that can self-evolve is always considered an engineering marvel. 6

The macroscopic signals that a cell receives from its environment can influence which genes it expresses — and thus which proteins it contains at any given time — or even the rate of mutation of its DNA, which could lead to changes in the molecular structures of the proteins. 8

The genome has traditionally been treated as a Read-Only Memory (ROM) subject to change by copying errors and accidents. 7  I propose that we need to change that perspective and understand the genome as an intricately formatted Read-Write (RW) data storage system constantly subject to cellular modifications and inscriptions. Cells operate under changing conditions and are continually modifying themselves by genome inscriptions. These inscriptions occur over three distinct time-scales (cell reproduction, multicellular development and evolutionary change) and involve a variety of different processes at each time scale (forming nucleoprotein complexes, epigenetic formatting and changes in DNA sequence structure). Research dating back to the 1930s has shown that genetic change is the result of cell-mediated processes, not simply accidents or damage to the DNA. This cell-active view of genome change applies to all scales of DNA sequence variation, from point mutations to large-scale genome rearrangements and whole genome duplications (WGDs). This conceptual change to active cell inscriptions controlling RW genome functions has profound implications for all areas of the life sciences.

Ever since the formulation of the neo-Darwinist Modern Synthesis evolutionary theoryin the 1930s and 1940s, it has been an article of faith that hereditary variation results from stochastic copying errors and unavoidable damage to the genome

In the past 60 years, since the structure of DNA was elucidated, molecular biologists have studied the basic mechanisms of long-term genome change. They have discovered a wide array of proofreading and damage repair biochemical systems that remove copying errors and correct DNA damage. At the same time, they have revealed an amazing and wholly unanticipated array of cellular and molecular systems that operate to generate genome variability, both temporary and structural. As we begin the second decade of the 21st century, accumulating empirical evidence has thus shifted the perspective on genome variation to that of an active inscription process changing the information passed on to future generations.

Mutation 1

It is clear that new gene alleles are accumulating in populations today, but there are two possible sources for these changes; mutations, and intentional changes introduced by genetic recombination. The theory of evolution attributes the continued production of genetic diversity to mutations, but evolutionists overlook the fact that the cell was intelligently designed. The cellular machinery was programmed to perform a level of self genetic engineering, and is editing genes systematically so that organisms can adapt to a wide variety of environmental conditions.

Evolutionists contend that mutation, acted upon by natural selection is the mechanism for evolutionary advancement. While this mechanism has the power to change the genome over time, most biological evolution is actually due to genetic recombination followed by natural selection. There are many examples put forward by evolutionary biologists that attempt to show how new genes have been introduced into the genome of an organism. However, in most documented cases it merely illustrates the built-in plasticity or variation within the original created kind. Merely shuffling of already existing genes becomes woefully inadequate if the observational science is followed.
Despite the few examples of beneficial genetic mutations it is unrealistic to assume that this information produced through changing already existing DNA would then be acted on again many more times by other related mutations to build radically different and complex structures than what was there previously. This is to say that mutations are not a reasonable means of producing cascading morphological change from one kind of animal to another but merely speciation.

Biophysicist Dr. Lee Spetner in his book, Not by Chance: Shattering the Modern Theory of Evolution, analyzed examples of mutational changes that evolutionists claimed were increases in information, and demonstrated that they were actually examples of loss of specificity, meaning loss of information.
“ In all the reading I've done in the life-sciences literature, I've never found a mutation that added information. … All point mutations that have been studied on the molecular level turn out to reduce the genetic information and not increase it." - Spetner ”
“ We see then that the mutation reduces the specificity of the ribosome protein and that means a loss of genetic information. ... Rather than saying the bacterium gained resistance to the antibiotic, it is more correct to say that is lost sensitivity to it. ... All point mutations that have been studied on the molecular level turn out to reduce the genetic information and not increase it.

Georgia Purdom, Ph.D. of molecular genetics, has stated,

“ Mutations only alter current genetic information; they have never, ever been observed to add genetic information; they can only change what is there. I have a lot of papers come across my desk of supposedly mutations that have added genetic information, and I've read them all, and I've looked at them all, and never, once have I seen one that has added genetic information; they just don't do that.

Nonrandom mutations 4

Mutations are supposed to be accidental, undirected events that are in no way adaptive. For example, if an animal species needs thick fur to survive in a cold climate, it will not respond by growing fur; rather, any animals who undergo random genetic changes that happen to result in thick fur will survive to produce more offspring. As Robert Gilson says, ‘The doctrine of random variation is just as unprovable as is the doctrine of the Virgin Birth, and just as sacrosanct to its adherents.’1

Attempts to justify the doctrine of random mutations usually refer to a series of experiments on the bacterium E. coli in the late 1940s and early 50s. These experiments found that when bacterial cells are suddenly subjected to a particular selection pressure (e.g. the addition of a lethal antibiotic), a small proportion of cells invariably survive because they contain a mutation that confers resistance to the antibiotic. Tests were then carried out which proved that the mutations were present in the surviving cells before the antibiotic was added to the culture, and that they were therefore truly spontaneous and nonadaptive. However, the original researchers recognized that this did not rule out the possibility of adaptive, nonrandom mutations.2

More recent experiments have shown that mutations can indeed occur in direct response to an environmental challenge – and have aroused great controversy.3 It has been found that bacteria which are unable to digest lactose, if given no other food, will after a few days develop new mutants that are able to handle it, the mutation rate being many orders of magnitude faster than the ‘spontaneous’, ‘random’ rate. Two independent mutations were needed, giving an ‘accidental’ explanation a probability of less than 1 in 10^18. Adaptive mutations also appear to occur in yeast cells and possibly fruit flies.4 The existence of adaptive mutations is now widely accepted, though the term ‘directed mutations’ is sometimes shunned. Although some of the biochemical mechanisms involved have been identified, there is no real understanding of what lies behind the phenomenon.

According to Eshel Ben-Jacob and his colleagues, ‘a picture of problem-solving bacteria capable of adapting their genome to problems posed by the environment is emerging’; ‘It seems as if the bacterial colony can not only compute better than the best parallel computers we have, but can also think and even be creative.’5 As James Shapiro has said, even the ‘simplest’ form of life – tiny, ‘brainless’ bacteria – ‘display biochemical, structural and behavioral complexities that outstrip scientific description’.6

The rapidity with which pests, from rats to insects, acquire resistance to poisons is also hard to account for on the basis of conventional evolutionary theory. Some 500 species of insects and mites have been able to defeat at least one pesticide by genetic changes that either defensively alter the insect’s physiology or produce special enzymes to attack and destroy the poison. 17 have shown themselves capable of resisting all chemicals deployed against them. As Robert Wesson says, ‘If it is true that mutations are much more frequent where they are needed than when they are virtually certain to be harmful, they cannot be held to be random.’7 Shapiro states that ‘All careful studies of mutagenesis find statistically significant nonrandom patterns of change ...’8

Molecular biologist Lynn Caporale points out that mutations seem to occur preferentially in certain parts of the genome while other DNA sequences tend to be conserved – which shows, she says, that evolution is not purely a game of chance. Although she believes that genomes can ‘steer’ mutations to ‘hot spots’ where they are more likely to increase fitness, and that the genome may be ‘in some way intelligent’, she does not believe that the actual mutations themselves are nonrandom in the sense of being somehow engineered by the organism in question to bring about the changes it needs.9 This is a good example of how Darwinists sometimes dress up their dogmas in ‘sexy’ and even mystical-sounding language.

the randomness of mutations has been called into question since the 1970s in experiments demonstrating that cells subject to non-lethal selection come up repeatedly with just the  right ‘adaptive’ or ‘directed’ mutations in specific genes that enable the cells to grow and multiply 5

8 )

Last edited by Admin on Fri Jan 03, 2020 11:26 am; edited 8 times in total


Nonrandom Mutations Scramble the Case for Common Descent 1

Non random mutations : How life changes itself: the Read-Write (RW) genome DNA-yellow-1
"Cowards die many times before their deaths; The valiant never taste of death but once." (Julius Caesar, 2.2.32–37)

New work by researchers from Great Britain reveals that mutation rates in the genome of E. coli are nonrandom and optimized to minimize their impact on survival. This optimization adds to the case for intelligent design. Moreover, it challenges a key assumption made by evolutionary biologists, namely that shared DNA sequences in the genome of related organisms serves as evidence for common descent and, consequently, biological evolution.

They say death and taxes are the only two things certain in life. But in biology, there is a third inevitability: mutations. Changes will happen in an organism’s genetic material and, as a result, the DNA sequences of the genome will be altered. 
Although evolutionary biologists regard mutations as the engine that drives the evolutionary process, more often than not, mutations are deleterious to the organism. These scientists have long thought that mutations occur in genomes randomly. Natural selection fixes into the population the few mutations that increase the organism’s fitness. But a recent study indicates that organisms can manage mutations, much in the same way an accountant structures finances to reduce the amount of taxes a client owes.
This newly recognized ability challenges one of the key assumptions evolutionary biologists employ when interpreting genomes’ shared features as evidence for common descent and, hence, biological evolution. On the other hand, this discovery can be rightly enlisted to further the case for intelligent design.

Nonrandom Mutations in E. coli

By analyzing and comparing the genomes of 30 E. coli strains, researchers from Great Britain discovered that the mutation frequency varies across this bacterium’s genome.1 Some regions (hot spots) have a relatively high mutation rate; others (cold spots) display a relatively low rate of genetic change.
The researchers learned that hot and cold spot locations are not random. Hot spots occur in regions where mutations would do the least amount of damage. Meanwhile, cold spots show up in areas that harbor genes critical for E. coli’s survival. The hot and cold regions both typically encompass large stretches containing genes that are part of the same operon. These neighboring genes often encode proteins that participate in the same cellular processes.
Additionally, the researchers determined that cold spots tend to occur in highly expressed genes. Yet because transcription (which dictates, in part, the rate of gene expression) tends to cause mutations, it seems that hot spots should associate with highly expressed genes. This surprising result indicated to the investigators that there must be some mechanism that actively manages the mutation rate, compensating for the transcriptional process’s mutagenicity.
Thus, it appears that the mutation rates across genomes have been optimized to reduce the risk of harmful genetic changes. Although the nonrandom distribution of mutations in genomes is contrary to the most common understanding of evolutionary theory, it is not surprising to learn that mutation rates and the location of mutational hot and cold spots are optimized to protect E. coli from the loss of fitness. Biochemical systems are characteristically optimized. It is reasonable to think that, if mutation rates across the E. coli genome have been optimized to minimize damaging effects, then the rates are optimized similarly in other organisms’ genomes.
This result is consistent with research that demonstrates that substitution mutations and recombination are nonrandom and take place in hotspots. Other studies also show that other genome-altering processes (such as intron insertion and transposon insertion) are nonrandom, occurring in hot spots, as well.

Nonrandom Mutations and the Case for Design
As I discussed in my book The Cell’s Design, the characteristic features of life’s chemistry are the same as what we would recognize as evidence for a human designer’s work. So, by analogy, it is logical to conclude that a Mind was responsible for bringing life into existence. Systems, objects, devices, etc., designed by humans are often optimized. In fact, optimization connotes high quality and superior designs. As such, the optimization of mutation rates can be seen as further evidence for intelligent design in nature. The distribution of hot and cold spots across the genome and association of cold spots with genes critical for survival portrays an elegance and cleverness that bespeaks of a Creator’s handiwork.
Nonrandom mutation rates also raise questions about the validity of a key assumption made by evolutionary biologists when they interpret shared features of genomes as evidence for common descent.

The Challenge for Biological Evolution
Evolutionary biologists consider identical (or nearly identical) DNA sequence patterns found in the genomes of related organisms as evidence of descent from a shared ancestor. According to this line of reasoning, the shared patterns arose as a result of mutational events that occurred in the common ancestor’s genome. Presumably, as the varying evolutionary lineages diverged from the nexus point, they carried with them the altered sequences created by the primordial mutations. This interpretation rests on the underlying assumption that the mutations that generated the shared fingerprint are rare and random.
But, if the mutations are nonrandom—preferentially taking place in hot spots—then it could be asserted that the DNA sequence patterns were generated independently in the separate biological groups. That is, the shared DNA sequence patterns may not be the result of descent with modification from a common ancestor, but instead arose separately. In other words, shared DNA sequences are not necessarily evidence for common descent and biological evolution.
Death and taxes may be a given, but the case for biological evolution is far from certain.



James Shapiro’s talk, clearly one of the most interesting of the conference, highlighted this difficulty in its most fundamental form. Shapiro presented fascinating evidence showing, contra neo-Darwinism, the non-random nature of many mutational processes – processes that allow organisms to respond to various environmental challenges or stresses. The evidence he presented suggests that many organisms possess a kind of pre-programmed adaptive capacity – a capacity that Shapiro has elsewhere described as operating under “algorithmic control.” Yet, neither Shapiro, nor anyone else at the conference, attempted to explain how the information inherent in such algorithmic control or pre-programmed capacity might have originated.


Evolution - A View from the 21st Century
James A. Shapiro

Natural genetic engineering represents the ability of living cells to manipulate and restructure the DNA molecules that make up their genomes.

To date, all studies of genetically modified organisms have required an intact cell structure for the introduction of new genetic information by DNA or nuclear transplantation. So there is no unequivocal empirical basis for believing the frequent assertion that DNA contains all necessary hereditary information.

We still do not adequately understand the role that preexisting cell structures and organelles play in templating the formation of their descendants in progeny cells. In mammalian reproduction, for example, we know that both the sperm and the maternal environment contribute non-DNA factors to the fertilized egg and developing embryo. Simple reflection makes it obvious that a properly structured egg is essential to hereditary transmission in all “higher” organisms. Modifications of cell structure have been critical events at some of the most important stages of evolutionary innovation, and purely DNA-based explanations are insufficient to describe them in a scientifically comprehensive way. In ciliate protozoa, in the mid-20th Century, Tracy Sonneborn did pioneering work on genome-independent heredity of the cell cortex

For over six decades, however, an increasingly prevalent alternative view has gained prominence. The alternative view has its basis in cytogenetic and molecular evidence. This distinct perspective treats the genome as a read-write (RW) memory system subject to nonrandom change by dedicated cell functions

We can distinguish at least seven distinct but interrelated genomic functions essential for survival, reproduction, and evolution:

1. DNA condensation and packaging in chromatin
2. Correctly positioning DNA-chromatin complexes through the cell cycle
3. DNA replication once per cell cycle
4. Proofreading and repair
5. Ensuring accurate transmission of replicated genomes at cell division
6. Making stored data accessible to the transcription apparatus at the right time and place
7. Genome restructuring when appropriate

In all organisms, functions 1 through 6 are critical for normal reproduction, and (as you will see later) quite a few organisms also require function 7 during their normal life cycles. We humans, for instance, could not survive if our lymphocytes (immune system cells) were incapable of restructuring certain regions of their genomes to generate the essential diversity of antibodies needed for adaptive immunity. In addition, function 7 is essential for evolutionary change. This part of the book devotes considerable attention to discussing the numerous molecular modalities of genome restructuring discovered since the double helix structure of DNA was described in 1953.

From an evolutionary point of view, the main question to ask is how transcriptional regulatory circuits arise in the first place. How are similar binding sites amplified and distributed to multiple locations throughout the genome? How do higher-order circuit elements, enhancers, and more-complex cis-regulatory modules (CRMs) form and then disperse through the genome? These questions are distinct from those that evolutionists ask about the origins and diversification of coding sequences. We need to keep in mind that genomes contain many different kinds of information and that the entire cellular DNA has to evolve in a way that produces functional and adaptive expression systems. A little thought will make it clear how difficult it is to maintain the traditional idea that each individual component of these elaborate circuits evolves by making its own independent random walk through the enormous space of genome sequence possibilities. As you will see, there are alternative ways, based on established molecular processes, to think about the efficient evolution of genomic circuits based on rapid distribution of transcriptional regulatory sequence motifs.

Genome Compaction, Chromatin Formatting, and Epigenetic Regulation

For a few decades in the late 20th Century, it was possible to think that transcriptional regulatory circuits are sufficiently complex and sensitive to provide an adequate account of how cells regulate coding sequence access. However, two separate lines of thinking and experimentation taught us about additional layers of higher-order control on genome expression. Although originally independent, the two approaches converged at the molecular level in a surprising and satisfying way. This multilayered view of regulation enriches our ability to understand different aspects of genome function. It also turns out that it helps us account for the timing of evolutionary change in unexpected ways. The first line of thought had its origins in the problems posed by multicellular development and cellular differentiation. How do cells become different from each other? How do tissues composed of specialized cell types form? What principles drive tissue formation and morphogenesis down well-defined paths during embryonic development? Without any detailed knowledge of molecular mechanisms, but well versed in developmental genetics, Conrad Waddington theorized about an “epigenetic landscape” that “canalized” genome function during development.

Although described metaphorically in terms of surface grooves guiding marbles rolling down a hillside, this hypothetical concept has had lasting influence on researchers and has finally found a concrete molecular explanation. The term epigenetic means “beyond (or added to) genetics.” It refers to a mode of heredity independent of the basic DNA sequence or “genetic” constitution. This idea is useful in understanding multicellular development. It describes how certain groups of cells—say, in a particular tissue or organ—can share inherited characteristics while retaining the same genome as cells with distinct inherited characteristics in a different tissue or organ. Besides such theorizing about cell differentiation, several phenomena provided independent evidence for an additional mode of inheritance. Perhaps the most instructive of these cases is genetic imprinting, which in animals and flowering plants means that the expression of a genetic locus depends on whether it is inherited from the male or female parent. Certain genetic loci are expressed only from the copy inherited from the father and other loci only when inherited from the mother. In the mealy bug, where the term imprinting was first applied, the expression of a whole set of chromosomes inherited from the father is silenced in males but not in females. Somehow, during the formation of the sperm and egg cells, different genetic loci or even whole chromosomes are marked, or imprinted, for silencing in the next generation.

Although the imprinting of a particular locus changes as it passes through male or female gametes, the underlying genetic information does not change. Because the imprint remains throughout multicellular development, the imprinted state is heritable through numerous mitotic cell divisions. In the mealy bug example, and in many vertebrate and plant examples, broader regions of the genome encompassing multiple genetic loci or whole chromosomes can be imprinted. Thus, epigenetic inheritance represents a high-level control (or set of controls) that can extend to entire haploid genomes. Epigenetic inheritance can extend beyond the development of a single individual to encompass several, or even many, generations. For example, the transgenerational epigenetic changes in maize plants called paramutations involve no alteration of DNA sequence but are stably transmitted through sexual reproduction for many generations. Similar changes are found in animals. In rodents, certain environmental stimuli, which include chemicals that disrupt endocrine signaling in sexual development, induce transgenerational changes in the offspring that are inherited by their descendants. Such heritable changes have been ascribed to alteration of epigenetic modifications.

Comparable environmentally induced transgenerational changes have also been documented in plants. It has become evident that the epigenetic mode of inheritance exists in tandem with inheritance based exclusively on DNA sequences. For a small but growing number of scientists, the epigenome (the constellation of all epigenetic modifications in the nucleus) constitutes a primary interface between environmental factors and the genome. As we turn our attention to the molecular nature of epigenetic modifications, you will see how this interface operates. Later, you will learn how epigenetic controls connect genome restructuring functions to organismal life histories. The second line of research leading to our current understanding of epigenetics was experimentation in diverse fields on the relationship between DNA packaging into chromatin and replication and transcription. From early and mid-20th Century cytogenetics, it had been known that different chromosome regions stained distinctly and formed different types of chromatin (literally, “colored material”). Euchromatin (“true” chromatin) stained lightly and appeared to be the active region of the genome. Heterochromatin (“different” chromatin) stained darkly and was associated with silent regions of the genome (for example, the silenced paternal chromosomes in male mealy bugs). Genetic manipulations that placed an active genetic locus next to heterochromatic regions, such as centromeres, resulted in silencing of the previously active locus. This “position effect” indicated that heterochromatic silencing could spread relatively long distances in the genome. Position effect phenomena further indicated that location in the genome was an important factor in controlling expression. Many experiments have verified the importance of “genome context” in the expression of individual genetic loci.

In the late 20th and early 21st Centuries, the correlation between chromatin structure and functional expression was placed on a defined molecular basis. The packaging of DNA within the eukaryotic cell depends at the most basic nucleosome level on winding the negatively charged double helix around positively charged proteins called histones. A special sequence code helps position the histones along the DNA to form regularly spaced nucleosomes. There are two general differences between DNA and histones in euchromatin and heterochromatin: • Heterochromatic DNA is more heavily modified by methyl groups attached to the cytosine (C) bases in its sequence. • The histones in euchromatin and heterochromatin carry different chemical modifications (methyl, acetyl, and other chemical groups attached to particular amino acids in the histone “tails” that stick out from the nucleosomes). The histone modifications constitute what has come to be called a histone code; it allows molecular biologists to distinguish the chromatin state of associated DNA sequences. By examining  DNA methylation and histone modifications in active, silenced, and imprinted regions of the genome, a catalog is taking shape that allows us to identify the chromatin configurations associated with each epigenetic state of the genome. We already know from studies in yeast that the simple division into euchromatin and heterochromatin is too simple; chromatin configurations are specialized for different genomic functions.  Cells possess enzymes that either attach or remove methyl and acetyl groups from cytosines in DNA and exposed amino acid tails in histones. Thus, the formation or modification of chromatin structure is an active process with major consequences for the functional state of the underlying DNA. Such active chromatin reformatting is regulated by cell signaling circuits. It plays a major role in cell differentiation as cells become more specialized, silence large unused regions of their genomes by incorporation into silent heterochromatin, and open other regions encoding protein and RNA molecules needed for differentiated cell function. 

The ability of cells to target chromatin formatting within the genome is aided by the recently discovered role of micro- and other noncoding RNA molecules (ncRNAs). Some of these ncRNAs form a complex with specialized RNA binding proteins linked to the enzymatic machinery for chromatin reformatting and specifically alter chromatin in the regions that have sequences complementary to the ncRNA. You will see later how this RNA-targeted chromatin modifying/epigenetic regulation plays a critical role in the control of genome restructuring in response to episodes of cell stress or genome shock. Barbara McClintock used this phrase in speaking to explain a challenge or stress event that provoked a cell to activate the molecular systems that restructure genomes. The indexing of the genome into extended chromatin domains that may encompass dozens of genetic loci and hundreds of thousands of base pairs is itself subject to additional formatting. We have learned about the existence of various classes of insulator sequences, which serve as boundaries between different types of chromatin . They also separate transcriptional formatting signals, such as promoters and enhancers. Some insulators nucleate insulator bodies that attach chromosomes to the nuclear envelope and thereby create a barrier to extension of chromatin domains. Other insulators work by directing RNA PolIII transcription of SINE or tRNA molecules and thus moving their chromosome site into one of many specialized transcription factories within the functionally compartmentalized nucleus. Certain sequences format the initiation of silent chromatin domains. In general, these are repetitive DNA sequences recognized by ncRNAs. These silent chromatin formatting sequences will become important when we discuss the impact that genome restructuring has
on the expression of stored information.

Genome Formatting for Replication, Localization, and Transmission to Daughter Cells

To function effectively as a storage medium in proliferating cells, replicated DNA molecules must pass reliably to progeny cells at division. We have already discussed the role of checkpoint surveillance routines in ensuring the accuracy of this process in eukaryotic cells. As is the case for transcriptional regulation, DNA molecules must be formatted by the appropriate signals for a complete replication process, for proper localization during the cell cycle, and for accurate transmission at division. Several different functional types of formatting signals are involved in integrating these biochemical and biomechanical events into the cell cycle:
• Sites for initiating DNA replication. In prokaryotes these are called origins of replication, or ori sites. For the basic genomic components, there is generally one ori per molecule. Ori sites tend to have a composite organization that includes multiple recognition sequences related to the control circuitry that ensures there is only one initiation event per cell division cycle. In eukaryotes, these initiation sites are called autonomous replication sequences (ars) and exist at multiple locations in each of the chromosomes. The ars sites are less defined in eukaryotes than Ori sites in prokaryotes, although  recent work has begun to discern characteristic motifs. They interact with an origin of replication complex (ORC) multiprotein apparatus that is connected to the cell cycle control circuitry so that each ars sequence can only initiate replication once per S phase of each cell cycle.
• Sites for completing DNA replication. In prokaryotes, these assume a variety of forms. Many of the prokaryotic DNA molecules are circular in structure and contain special terminus regions that have signals for biochemical processes that allow the replicated molecules to form completed duplexes and separate from each other if they have become interlocked or joined into a single double circle. Some prokaryotes have linear DNA molecules with closed hairpin ends connecting the two strands (also found in some viruses). The hairpin ends contain signals that facilitate the “resolution” of daughter molecules by a special recombination event as soon as the hairpin has been replicated. In eukaryotes, the chromosomal DNA molecules are linear with open ends, which poses two problems for maintenance and replication:
i. The ends must be prevented from joining, in the same way that ends do for some forms of double-strand (DS)
break repair.
ii. The replication apparatus can copy only one DNA strand completely, leaving the other strand incomplete. These two problems are solved by constructing a special telomere (literally, “end body”) structure at each extremity of the chromosomal DNA molecule. The telomere contains a number of different signals that facilitate the addition of extra DNA sequences to the end after replication (usually involving the enzyme telomerase but sometimes employing other mechanisms). They also format a special telomeric chromatin structure that protects against end-to-end joining by DNA repair functions.
• Sites for ensuring transmission at cell division. In prokaryotes, these generally are labeled partition (par) sites. The par sites ensure separation of replicated DNA molecules and movement to the cell poles, powered by an actin-related motor protein, so that the two copies end up in separate cells after division in the middle of the cell. In eukaryotes, chromosome separation is formatted by the centromere (literally, “central body”) or cen sequence. In most eukaryotes, centromeres are complex structures containing many tandemly repeated DNA sequence elements. These format a special centromeric heterochromatin structure that undergirds assembly
of the kinetochore structure, which in turn attaches to the microtubules of the spindle apparatus. This ensures separation

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