Genome and evolvability: study layers that modify (Introduction)

by David Turell , Monday, September 28, 2020, 19:55 (1313 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.

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"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.

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"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.

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"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.

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"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.