Genome and evolvability (Introduction)

by David Turell @, Friday, January 09, 2015, 20:18 (3367 days ago)

A review of Wagner's book, Arrival of the Fittest which explains Wagner's concepts, and foolishly tries to make evolution seem easy. There is no explanation for the start of life, but it does show pattern networking in the genome which can realistically make the whole process easier. The concluding paragraph raised the question of the information necessary, and no explanation of where the info came from.-"And gene circuits? Same story. Wagner has collaborated with physicist Olivier Martin to explore the space of hypothetical gene regulatory networks. They searched for different networks that, by mutually regulating the activity of the constituent genes, would produce the same overall patterns of gene expression— that is, the same phenotype.4 To take a trivial example, in a network of three genes A, B, and C, the same result of switching off expression of gene B could be achieved by either A or C inhibiting B. Even for just a dozen or so genes the number of possible networks of interactions becomes too vast for an exhaustive search, and so the researchers could examine only a tiny region of the space. But the outcome was clear: On the one hand, circuits typically have dozens to hundreds of neighbors with the same phenotype, while on the other hand circuits that differed in more than 90 percent of their “wires” could still produce the same expression pattern.-"This helps to explain a puzzling aspect of gene circuits: their robustness. In the late 1990s a team of researchers at Stanford University created around 6,000 mutants of brewer's yeast, each of them lacking a different single gene, and found that many of them thrived just as well as the unmutated yeast did.5 The same proves to be true for many other organisms: You can obliterate many of their individual genes to no obvious effect. But this is no surprise if there are plenty of similar gene circuits that do much the same job as the original one. Looked at this way, robustness is complementary to innovation: Any network that can evolve new features and forms among a vast array of alternatives must necessarily be robust against small changes, because it almost certainly has an alternative on hand that performs equally well. This realization offers an antidote to an excessively deterministic view of genes: Exactly which genes you have may not matter so much (within reason), because the job they do is more a property of the network in which they are embedded.-........-"Manrubia agrees that complexity is the key. “It seems clear that efficient navigability can only be achieved in genotype spaces of high dimensionality,” she says. That simply puts more options in reach—because you have more directions to reach in. “As the number of possible neighbors of a sequence increases, the likelihood that some of those neighbors has a viability comparable to the original one grows.” One consequence, she says, is that there could be an adaptive imperative favoring larger genomes, at least for organisms inhabiting varying environments: That way, you gain more in robustness than you lose in the labor of replicating and maintaining a lot of DNA.-"These ideas suggest that evolvability and openness to innovation are features not just of life but of information itself. That is a view long championed by Schuster's sometime collaborator, Nobel laureate chemist Manfred Eigen, who insists that Darwinian evolution is not merely the organizing principle of biology but a “law of physics,” an inevitable result of how information is organized in complex systems. And if that's right, it would seem that the appearance of life was not a fantastic fluke but almost a mathematical inevitability."-http://nautil.us/issue/20/creativity/the-strange-inevitability-of-evolution

Genome and evolvability: a DNA timer for mutations

by David Turell @, Monday, February 05, 2018, 20:12 (2244 days ago) @ David Turell

A mechanism that allows for copy mistake mutations is found. This will drive the process of evolution:

https://www.sciencedaily.com/releases/2018/01/180131133343.htm

"Scientists have discovered that the helical structure of DNA contains a kind of built-in timer that determines the frequency at which specific mutations spontaneously occur. They show that certain DNA bases can shape-shift for a thousandth of a second, transiently morphing into alternative states that can allow the replication machinery to incorporate the wrong base pairs into its double helix. Such mismatches, though rare, could serve as the basis of genetic changes that drive evolution and diseases, including cancer.

***

"The study, published in a 2015 issue of Nature, showed the bases G and T nudging aside the atoms on their surface so they could connect like puzzle pieces. The researchers found that these rearrangements came in different varieties, called "tautomeric" and "anionic" forms, though it wasn't clear which ones were responsible for replication errors.

***

"Together with their collaborators at The Ohio State University, they fed their NMR data into a "kinetic model" that traced the nearly invisible movements taken by the atoms in the mismatches that result in replication errors. They found that, though the different alternative states each contributed to errors, the tautomeric forms dominated under normal conditions and the anionic forms dominated in the presence of mutagens and environmental stress.

"'In the past, we knew DNA polymerases make mistakes during DNA replication but did not know how they do it," said Zucai Suo, Ph.D., Ohio State professor of chemistry and biochemistry. "Now, our study provides a mechanistic sense for how the mistakes arise."

"The results provide "convincing validation for the chemical origins of mutations proposed by Watson and Crick in 1953," said Myron Goodman, Ph.D., a professor of molecular biology and chemistry at the University of Southern California, who was not involved in the study. "It is significant scientifically, and even though it took about 65 years to prove, it also demonstrates the folly of ever betting against Watson and Crick."

"The textbook depiction of the iconic double helix shows a static double-stranded structure, but it turns out that on rare occasions it can morph into other shapes that exist for exceptionally small periods of time," Al-Hashimi said. "Though some might question the importance of such states, there are a growing number of studies showing they can be major drivers of biology and disease.

***

"One of the surprising discoveries made by the team was that the frequency at which bases shifted their shapes varied with DNA sequence. In one of their experiments, Ohio State biochemists Zucai Suo and Walter Zahurancik essentially counted the number of times that polymerases incorporated the wrong base into the DNA. They found that mistakes were indeed not uniform: they appeared more frequently in some sequences than others. For example, a region with more Gs and Cs might form more quantum jitters, and subsequently more mutations, than an area that was rich in As and Ts.

"The quantum jitters may be responsible not only for errors in replication, but also in other molecular processes such as transcription, translation, and DNA repair."

Comment: If God designed how DNA works, He would have certainly put in this mechanism to drive evolution.

Genome and evolvability: layers that modify

by David Turell @, Wednesday, February 07, 2018, 19:52 (2242 days ago) @ David Turell

Described in this article:

http://www.rna-networks.at/about/

"For more than half a century it has been accepted that new genetic information is mostly derived from random‚ error-based’ events. Now it is recognized that errors cannot explain genetic novelty and complexity.

"Empirical evidence establishes the crucial role of non-random genetic content editors such as viruses and RNA-networks to create genetic novelty, complex regulatory control, inheritance vectors, genetic identity, immunity, new sequence space, evolution of complex organisms and evolutionary transitions.

"Genetic identities of RNA stem loop groups (RNA-networks) such as e.g., group I introns, group II introns, viroids, RNA viruses, retrotransposons, LTRs, non-LTRs and subviral networks such as SINEs, LINEs, Alus invade and even persist in host genomes. Also mixed consortia of RNA- and DNA-virus derived parts that integrate in host genomes have been found. Highly dynamic RNA-Protein networks such as Ribosome, Editosome and Spliceosome generate a large variety of results out of DNA content.

"Genome invading agents such a viruses and RNA-networks represent a very large and dynamic source of genetic novelty. They can co-operate, build communities, generate nucleotide sequences de novo and insert/delete them into host genetic content. Viruses and RNA-networks often remain as mobile genetic elements or similar ‚defectives’ and determine host genetic identities throughout all kingdoms including the virosphere. But inclusion of a transmissive viral biology differs fundamentally from conventional thinking in that it represents a vertical domain of life providing vast amounts of linked information not derived from direct ancestors.

"This new empirically based perspective on the evolution of genetic novelty will have more explanatory power in the future than the „error-replication“ narrative of the last century."

Comment: this summarizes the most recent voluminous findings of activities that influence the genome and the transmission of information. The genome then is less of a pristine descending tree of common descent than one that has influences coming in from the outside of the tree working with previous developments and based on the past, pushing evolution into new directions. Could easily be the way God dabbles! Thus it looks like simple common descent, specifically linked entirely to the past, but really isn't. Darwin doesn't fit, but there is no way he could have imagined all these hidden influences which destroy his theory of mechanism.

Genome and evolvability: layers that modify

by dhw, Thursday, February 08, 2018, 14:14 (2241 days ago) @ David Turell

DAVID: Described in this article:
http://www.rna-networks.at/about/

QUOTE: "For more than half a century it has been accepted that new genetic information is mostly derived from random‚ error-based’ events. Now it is recognized that errors cannot explain genetic novelty and complexity.”

You and I have long since agreed that errors cannot explain innovation!

QUOTE: Genome invading agents such a viruses and RNA-networks represent a very large and dynamic source of genetic novelty. They can co-operate, build communities, generate nucleotide sequences de novo and insert/delete them into host genetic content. Viruses and RNA-networks often remain as mobile genetic elements or similar ‚defectives’ and determine host genetic identities throughout all kingdoms including the virosphere. But inclusion of a transmissive viral biology differs fundamentally from conventional thinking in that it represents a vertical domain of life providing vast amounts of linked information not derived from direct ancestors.

DAVID: The genome then is less of a pristine descending tree of common descent than one that has influences coming in from the outside of the tree working with previous developments and based on the past, pushing evolution into new directions. Could easily be the way God dabbles! Thus it looks like simple common descent, specifically linked entirely to the past, but really isn't. Darwin doesn't fit, but there is no way he could have imagined all these hidden influences which destroy his theory of mechanism.

By definition a novelty will provide information not derived from direct ancestors, but each novelty will still have to occur in existing organisms unless you believe in a God who creates every new organism from scratch. Cooperation was a major feature of Lynn Margulis’s interpretation of evolution, and it makes perfect sense that if an “invading agent” brings benefit to the host, the novelty will survive. The novelty is not “linked entirely to the past” – how could it be? – but evolution is a process by which existing organisms change into different organisms through innovation. The host provides the transition of descent from previous form to new. I agree yet again that Darwin’s mechanism of random mutations doesn’t work, but these “hidden influences” do not in any way undermine his theory of common descent. What you have called the "basic patterns" remain, and influences both hidden and open may determine what new forms they take.

Genome and evolvability: layers that modify

by David Turell @, Thursday, February 08, 2018, 18:40 (2241 days ago) @ dhw

QUOTE: Genome invading agents such a viruses and RNA-networks represent a very large and dynamic source of genetic novelty. They can co-operate, build communities, generate nucleotide sequences de novo and insert/delete them into host genetic content. Viruses and RNA-networks often remain as mobile genetic elements or similar ‚defectives’ and determine host genetic identities throughout all kingdoms including the virosphere. But inclusion of a transmissive viral biology differs fundamentally from conventional thinking in that it represents a vertical domain of life providing vast amounts of linked information not derived from direct ancestors.

DAVID: The genome then is less of a pristine descending tree of common descent than one that has influences coming in from the outside of the tree working with previous developments and based on the past, pushing evolution into new directions. Could easily be the way God dabbles! Thus it looks like simple common descent, specifically linked entirely to the past, but really isn't. Darwin doesn't fit, but there is no way he could have imagined all these hidden influences which destroy his theory of mechanism.

dhw: By definition a novelty will provide information not derived from direct ancestors, but each novelty will still have to occur in existing organisms unless you believe in a God who creates every new organism from scratch. Cooperation was a major feature of Lynn Margulis’s interpretation of evolution, and it makes perfect sense that if an “invading agent” brings benefit to the host, the novelty will survive. The novelty is not “linked entirely to the past” – how could it be? – but evolution is a process by which existing organisms change into different organisms through innovation. The host provides the transition of descent from previous form to new. I agree yet again that Darwin’s mechanism of random mutations doesn’t work, but these “hidden influences” do not in any way undermine his theory of common descent. What you have called the "basic patterns" remain, and influences both hidden and open may determine what new forms they take.

Once again, we are in general agreement.

Genome and evolvability: layers that modify

by David Turell @, Thursday, April 23, 2020, 00:42 (1436 days ago) @ dhw

A fascinating new paper that tries to upend current thought:

https://phys.org/news/2020-04-dna-life-bookjust-jumbled-ingredients.html

"In two new papers, Jose argues that DNA is just the ingredient list, not the set of instructions used to build and maintain a living organism. The instructions, he says, are much more complicated, and they're stored in the molecules that regulate a cell's DNA and other functioning systems.

"Jose outlined a new theoretical framework for heredity, which was developed through 20 years of research on genetics and epigenetics, in peer-reviewed papers in the Journal of the Royal Society Interface and the journal BioEssays.

***

"Jose's argument suggests that scientists may be overlooking important avenues for studying and treating hereditary diseases, and current beliefs about evolution may be overly focused on the role of the genome, which contains all of an organism's DNA.

"'DNA cannot be seen as the 'blueprint' for life," Jose said. "It is at best an overlapping and potentially scrambled list of ingredients that is used differently by different cells at different times.

"For example, the gene for eye color exists in every cell of the body, but the process that produces the protein for eye color only occurs during a specific stage of development and only in the cells that constitute the colored portion of the eyes. That information is not stored in the DNA.

"In addition, scientists are unable to determine the complex shape of an organ such as an eye, or that a creature will have eyes at all, by reading the creature's DNA. These fundamental aspects of anatomy are dictated by something outside of the DNA.

"Jose argues that these aspects of development, which enable a fertilized egg to grow from a single cell into a complex organism, must be seen as an integral part of heredity. Jose's new framework recasts heredity as a complex, networked information system in which all the regulatory molecules that help the cell to function can constitute a store of hereditary information. (my bold)

***

"'Understanding the transmission, storage and encoding of biological information is a critical goal, not only for basic science but also for transformative advances in regenerative medicine," Levin said. "In these two papers, Antony Jose masterfully applies a computer science approach to provide an overview and a quantitative analysis of possible molecular dynamics that could serve as a medium for heritable information." (my bold)

"Jose proposes that instructions not coded in the DNA are contained in the arrangement of the molecules within cells and their interactions with one another. This arrangement of molecules is preserved and passed down from one generation to the next.

"In his papers, Jose's framework recasts inheritance as the combined effects of three components: entities, sensors and properties.

"Entities include the genome and all the other molecules within a cell that are needed to build an organism. Entities can change over time, but they are recreated with their original structure, arrangement and interactions at the start of each generation.

"That aspect of heredity, that the arrangement of molecules is similar across generations, is deeply underappreciated, and it leads to all sorts of misunderstandings of how heredity works," Jose said.

"Sensors are specific entities that interact with and respond to other entities or to their environment. Sensors respond to certain properties, such as the arrangement of a molecule, its concentration in the cell or its proximity to another molecule.

"Together, entities, sensors and properties enable a living organism to sense or 'know' things about itself and its environment. Some of this knowledge is used along with the genome in every generation to build an organism.

***

"The folly of maintaining a genome-centric view of heredity, according to Jose, is that scientists may be missing opportunities to combat heritable diseases and to understand the secrets of evolution.

***

"In evolution, Jose's framework suggests that organisms could evolve through changes in the arrangement of molecules without changes in their DNA sequence. And in conservation science, this work suggests that attempts to preserve endangered species through DNA banks alone are missing critical information stored in non-DNA molecules." (my bold)

comment: It's about time this appeared. All along I've said there are many other layers to the genetic controls, as in the last bold. Note the two bolds about the use of stored biological information. This quote is prophetic: "DNA cannot be seen as the 'blueprint' for life," Jose said. "It is at best an overlapping and potentially scrambled list of ingredients that is used differently by different cells at different times." So is this: "Jose proposes that instructions not coded in the DNA are contained in the arrangement of the molecules within cells and their interactions with one another."

Genome and evolvability: layers that modify in first life?

by David Turell @, Saturday, April 25, 2020, 17:27 (1434 days ago) @ David Turell

When I noted the last article, I am not surprised when I now see the ID community so excited in their comments which tuned up other articles of which I was not aware:

https://blogs.scientificamerican.com/observations/dna-is-not-a-blueprint/

"In the enthusiasm surrounding the progress of genomics, we end up overstating the real nature of our DNA and believing that it is more important than it is. The Oscar for Genetic Ravings goes to Advanced Technologies, an Indian DNA company whose website claims that genetic code is a “Divine Writing,” but genetic determinism—the idea that DNA will determine our fate and identity—is deeply ingrained in our culture. Make a Google search, and you’ll find hundreds of sources (including textbooks and leading scientists) describing DNA as the blueprint of life. It would be a great, easy-to-understand analogy, if it wasn’t wrong and outdated.

"DNA is not a blueprint: it’s a recipe coding for thousands of different proteins that interact with each other and with the environment, just like the ingredients of a cake in an oven. Whereas a blueprint is an exact, drawn-to-scale copy of the final product, a recipe is just a loose plot that leaves much more room to uncertainty.

***

"Take two identical twins: they share the same DNA, and their embryos developed side-by-side in the same uterus. Yet, they have different tastes, characters and attitudes, and make different choices in life. When you read the DNA of twins, you find a duplicate copy of the same recipe, but two distinct personalities. Not what you would call a fixed plan.

"We do not inherit specific instructions on how to build a cell or an organ. Our DNA contains a list of biochemical ingredients (the proteins coded in the genes) and the basic rules for their assembly (some proteins are labeled as “master” and can control the activity of others, while others can start a dominolike cascade of events) but the pieces self-organize into biochemical pathways, cells and tissues without reading a manual. The genetic recipe for a cat will not give an elephant, but you can’t read the DNA of an individual and see a Mini-Me of his features.

***

"Make no mistake: some traits are indeed genetically programmed, and some diseases are deterministic: people with a pathogenic mutation in the CFTR gene will develop cystic fibrosis regardless of their lifestyle. Even abilities once considered only a matter of upbringing like language, abstract thinking and many behavioral traits have a significant genetic component. But it doesn’t mean that DNA always has the upper hand. The opposite is true: an overwhelming majority of our traits depend on the blending of many genetic and nongenetic factors and therefore are hard to predict from DNA.

***

"Powered by petabytes of data and intelligent algorithms, the genetic profiles of the future will be mighty, and their breadth will be frightening. Yet, no test will ever be able to predict our personalities accurately, not to mention our fates, because a significant part of what we are is not written into DNA."

Comment: another view showing the original simplistic interpretation of DNA's importance is gone. As we learn about our own genome and all its necessary hidden layers, we have gone from a kindergarten view to a position now where perhaps we are entering early high school in our knowledge. What it means to me is the simplistic view of origin of life is not correct. RNA naturally appearing on is own without all the other surrounding layers is poppycock. All of this integration of molecules influencing each other, some 'mastering' each other, cannot naturally be added layer by layer in a chance fashion to end up with life as we know it. This requires precise design by a designer. The existence of a designer cannot be denied no matter how that designer is named or not named. This is the ID position.

Genome and evolvability: layers that modify

by David Turell @, Saturday, September 26, 2020, 20:57 (1280 days ago) @ David Turell

New studies in birds show that gene expression is not predictable just from code appearance but can be modified by sexual state:

https://phys.org/news/2020-09-bird-genes-multitaskers-scientists.html

"Scientists from the University of Sheffield have found that although male and female birds have an almost identical set of genes, they function differently in each sex through a mechanism called alternative splicing.

"Males and females of the same bird species can be strikingly different. For example, in addition to fundamental differences in reproduction, the sexes can show profound variation in behavior, colouration, metabolism, disease incidence and life history.

***

"'One notable example of differences between male and female birds is in the peafowl, peacocks have magnificent plumage, whereas the female peahen is relatively dull. The peacock's long tail and bright colours evolved to help them attract mates, but having such eye-catching looks can come with negatives such as making them more noticeable to predators.

"'Features like this are beneficial to the males but may not be beneficial for females, so birds must find a way to evolve different characteristics. We predicted that the secret to these differences must lie in understanding how the same genes are expressed and function differently in males and females."

"Genes encode proteins, large complex molecules which drive processes in the body and are responsible for the function and structure of the body's tissues. Before genes can be used to make proteins, their DNA sequence is transcribed into RNA, an intermediary molecule that contains the instructions for making proteins.

"The scientists found that males and females differ in how bits of RNA are stitched together, meaning that the same gene can produce a large number of distinct proteins and functions depending on which sex the gene is expressed in. This process is called alternative splicing.

"Dr. Alison Wright, a researcher at the University of Sheffield and senior author of the study, said: "It is likely that this genetic process is really important for generating biodiversity, not only in birds but across the whole animal kingdom.'"

Comment: This is just a conformation of what we already know. 20,000 human genes have to be massively reinterpreted by alternative splicing to create us

Genome and evolvability: layers that modify

by David Turell @, Saturday, September 26, 2020, 21:02 (1280 days ago) @ David Turell

New studies in birds show that gene expression is not predictable just from code appearance but can be modified by sexual state:

https://phys.org/news/2020-09-bird-genes-multitaskers-scientists.html

"Scientists from the University of Sheffield have found that although male and female birds have an almost identical set of genes, they function differently in each sex through a mechanism called alternative splicing.

"Males and females of the same bird species can be strikingly different. For example, in addition to fundamental differences in reproduction, the sexes can show profound variation in behavior, colouration, metabolism, disease incidence and life history.

***

"'One notable example of differences between male and female birds is in the peafowl, peacocks have magnificent plumage, whereas the female peahen is relatively dull. The peacock's long tail and bright colours evolved to help them attract mates, but having such eye-catching looks can come with negatives such as making them more noticeable to predators.

"'Features like this are beneficial to the males but may not be beneficial for females, so birds must find a way to evolve different characteristics. We predicted that the secret to these differences must lie in understanding how the same genes are expressed and function differently in males and females."

"Genes encode proteins, large complex molecules which drive processes in the body and are responsible for the function and structure of the body's tissues. Before genes can be used to make proteins, their DNA sequence is transcribed into RNA, an intermediary molecule that contains the instructions for making proteins.

"The scientists found that males and females differ in how bits of RNA are stitched together, meaning that the same gene can produce a large number of distinct proteins and functions depending on which sex the gene is expressed in. This process is called alternative splicing.

"Dr. Alison Wright, a researcher at the University of Sheffield and senior author of the study, said: "It is likely that this genetic process is really important for generating biodiversity, not only in birds but across the whole animal kingdom.'"

Comment: This is just a conformation of what we already know. 20,000 human genes have to be massively reinterpreted by alternative splicing to create us. Note the bold as to why the peacock tail appeared. An obvious Darwinian just-so story. An obvious human thought with no scientific basis in realty.

Genome and evolvability: clear evidence of common descent

by David Turell @, Thursday, May 27, 2021, 20:39 (1037 days ago) @ David Turell

The control over chromosome architecture is very old:

https://science.sciencemag.org/content/372/6545/984?utm_campaign=toc_sci-mag_2021-05-27...

"The conformation of chromosomes within the nucleus can reflect a cell's type or state. However, studies of the conservation and evolutionary history of the mechanisms regulating genome structure across species are lacking. Hoencamp et al. mapped three-dimensional (3D) genome organization in 24 eukaryote species, including animals, fungi, and plants. At interphase, species' telomeres and centromeres either clustered across chromosomes or oriented in a polarized state maintaining individual chromosomal territories within the cell, a difference attributed to condensin II. An experimental loss of condensin II in human cells promotes the formation of centromere clusters but has no effect on loop or compartment formation. Whether the structure of the 3D genome varies across species may thus depend on whether they carry a functional condensin II gene.

"Abstract
We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes. (my bold)"

***

"Taken together, a model emerges in which condensin II establishes interphase 3D genome architecture at the scale of whole chromosomes. We hypothesize that (i) centromeres tend to adhere to one another, a process that is facilitated by proximity during and shortly after mitosis; (ii) the shortening of chromosomes interferes with this adhesion, enabling the centromeres to spread out over the newly formed nuclei; and (iii) chromosome territories emerge as a by-product of the resulting chromosomal separation.

"The role of condensin II in establishing the overall architecture of the genome appears to be among the most ancient capabilities defining genome folding in the eukaryotic lineage. Changes in condensin II have likely contributed to notable shifts from chromosome territories to Rabl-like features throughout the tree of life. As our exploration of the tree of life continues, one of the many fruits will be a deeper knowledge of our own cellular machinery."

Comment: That evolution is a continuum from start to now is clearly shown by studies of the evolution of the genome controls. God, as designer, makes it easy for Himself in creating common descent.

Genome and evolvability: study layers that modify

by David Turell @, Monday, September 28, 2020, 19:55 (1278 days ago) @ David Turell

James Shapiro returns with a book review:

https://inference-review.com/article/from-genes-to-genomes

"Genome Chaos is a book of no small ambition. Based on his experience in cancer cytogenetics, Henry Heng invites readers to rethink the role of the genome in determining the hereditary properties of cells and organisms. He distinguishes between gene-centric and genome-based views of heredity and argues that the physical organization of the genome incorporates a higher systems level of information beyond its genes or coding sequences. For Heng, genes are rather like a parts list capable of encoding proteins and RNAs that can be assembled and used in many different ways to produce cells and organisms with quite distinct properties. In making his argument, Heng challenges a number of notions about the genotype–phenotype relationship.

"According to Heng’s genome-based perspective, evolution can be broken down into two modes. Microevolutionary change operates within species much as Darwin envisaged, by “numerous, successive, slight modifications.”1 Macroevolutionary change rapidly restructures the genome to establish a new architecture, leading to new species and new phenotypes without changing the basic gene content.

***

"In Heng’s concept, it is the genome system properties of novel chromosome organizations and not specific gene content that drives the major steps in the evolution of all but a few exceptional cancers.

***

"Heng’s idea that genome system information is critical in taxonomic divergence has some interesting implications, notably the counter-conventional notion that the normal evolutionary function of sexual reproduction is to suppress, rather than enhance, major phenotypic variation within species. The need for meiotic chromosome pairing in the formation of gametes at each generation prevents individuals carrying germline chromosome changes from producing progeny who can pass on those changes.

"The most controversial aspect of Heng’s argument in Genome Chaos is the claim that specific gene-based changes play a minor role in the macroevolutionary process...Heng describes the absence of a strong, predictable consequence of single gene mutations as fuzzy inheritance. Single-gene changes evoke a weak effect because most organismal phenotypes result from the complex interaction of elaborate cellular networks, sensitive to both internal and external conditions. While a particular protein or RNA may participate in various networks, most major adaptive features of complex organisms are robust to defects in any single molecular component of those networks. Heng repeatedly emphasizes the importance of variability and heterogeneity for biological systems, features which clearly distinguish them from nonbiological systems.

***

"At numerous points throughout Genome Chaos, Heng urges researchers to reorient their thinking about basic evolutionary processes. He argues persuasively for a shift from a gene-based to a genome-based approach, a transition he describes as moving from a one-dimensional to a four-dimensional view of genomic information and function. The potential impact of such a transition highlights the many challenges arising from Heng’s proposal of a central role for karyotype change in both organismal and cancer cell evolution... Yet there is no comprehensive theory that accounts for how a given genome architecture facilitates the expression of particular phenotypes using the parts list specified by its coding sequences. Heng’s argument effectively places researchers in a position comparable to that of the pioneers of genetics in the early twentieth century.

***

"The case Heng makes for thinking about genomes rather than just genes is strong and convincing. By alerting the genomics community to a new scientific frontier, Genome Chaos accomplishes two important and complementary goals. It clearly demonstrates that a great deal of fundamental evolutionary biology and genetics research still needs to be done before newly acquired genomics and genome-editing technologies can be used to maximum advantage."

Comment: As usual I'm with Shapiro. All these years I've presented papers on complex genome layer actions and referred to 3-D relationships. We only have 20,000 genes and we are highly complex. The genome complex relationships is what creates us. We must study how to fully understand it.

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