Tuesday, June 09, 2015

Gene Regulatory Networks (GRNs): Major Collision at the Intersection of Evolution and Development

Q:        How does a fertilized egg cell give rise to such a variety of cell types as compose the body of a complex organism?

A:        That fertilized egg cell’s DNA arrived pre-loaded with the genetic information needed to craft the specialized cell types that compose the body of that complex organism.

Although each cell in that body inherits all of the fertilized egg cell’s genes, specific genes get switched on and off by other genes that produce regulatory molecules, and those genes are switched on and off by other genes and the molecules they produce according to what is needed for each type of cell. And all of this biochemical management occurs by feedback loops. The biochemistry that oversees the differentiation (and stabilization) of cell types in the developing organism is organized into gene regulatory networks (GRNs), very elaborate chemical feedback loops. 

The point to be made about GRNs is that, by regulating gene expression, the cellular machinery can coax from a highly conserved set of genes (those of the original fertilized egg) a liberal diversity of cell types (skin, muscle, nerve, etc.).

So far so good. But one noteworthy development is the increasing significance that evolutionary theorists ascribe to GRNs. Gene regulatory networks, not the acquisition of new genes, manage the differentiation of species from their common ancestors in much the same way as they manage the differentiation of cells in a body from their common ancestor, the fertilized egg cell. Diverse descendant phenotypes lurk within the DNA of ancestral genomes and genotypes alike, waiting to be switched on. 

The science of comparative genomics confirms a fundamental conservation of DNA across species, a finding that came as a surprise to everyone. The genetic similarities seen across species are too striking to sweep under the rug, and at least some researchers are candid about the new data’s impact on evolutionary theory. 

Charles R. Marshall, a biological science professor at the University of California, Berkeley, observes in a book review in the September 20, 2013 issue of Science,
"In fact, our present understanding of morphogenesis indicates that new phyla were not made by new genes but largely emerged through the rewiring of the gene regulatory networks (GRNs) of already existing genes"
This observation does double duty, because it also describes how a fertilized egg cell gives rise to descendant cell types. The descendant cell types emerge through the rewiring of gene regulatory networks.

Evidently, we can say that the genes for descendant species were there already in remote ancestors, or that the GRNs for descendant species were there already, or both were there already. In any case, what were they doing there? If they functioned one way, or were silent, in ancestors, how is it that they just happened to be re-wirable to produce highly dissimilar, yet “adapted,” descendants? That seems far fetched. But it makes sense and is to be expected if evolution is a case of development. It looks like GRNs manage the differentiation of species in an ecology in some manner similar to that in which such networks regulate the differentiation of cells in a body, namely by rearranging patterns of development.
Consider this adaptation of the quote above, "In fact, our present understanding of cellular differentiation in developing organisms indicates that new cell types are not made by new genes but largely emerge through the rewiring of the gene regulatory networks (GRNs) of already existing genes."
In Universal Genome in the Origin of Metazoa (Cell Cycle 6:15, August 2007) researcher Michael Sherman also argues that diverse species develop from a common, conserved, genome. His case rests largely on the presence of anomalous genes in ancestral species that are needed by descendant species, a circumstance called, pre-adaptation. He summarizes,
“In thinking about metazoan evolution, one should realize that any evolutionary event represents changes in developmental programs, rather than changes in a developed organism. [. . . .] This hypothesis postulates that (1) shortly (in geological terms) before [the] Cambrian period a Universal Genome that encodes all major developmental programs essential for every phylum of Metazoa emerged in a unicellular or a primitive multicellular organism; (2) The Metazoan phyla, all having similar genomes, are nonetheless so distinct because they utilize specific combinations of developmental programs. In other words, in spite of a high similarity of the genomes in phyla X and Y, an organism belonging to phylum X expresses a specific set of active developmental programs, while an organism belonging to a different phylum Y has a distinct set of “working” programs specific for phyla Y. This seemingly trivial statement changes the whole perception of evolution, claiming that the placement of an organism to a particular taxon depends on expression of a specific set of pre-existing developmental programs, rather than on difference in the genetic information per se. Therefore, within the Universal Genome model, what we perceive as a sequential evolution is actually a reflection of expression of one or another combination of programs from the Universal Genome. These postulates explain a simultaneous emergence of Metazoan phyla during [the] Cambrian period, as well as similarities of genomes and a dramatic increase in genome complexity in Metazoan phyla. [emphasis added]”
On just how it happened that the major developmental programs essential for every phylum of Metazoa emerged in a unicellular or a primitive multicellular organism the author does not speculate. But their presence there is to be expected, if evolution is an instance of development. The author’s characterization, elsewhere in the article, of developmental algorithms that wait in the wings as harboring “excessive” genetic information might be rendered more accurately as their harboring anticipatory genetic information.

Already in 1999, researcher W. H. Holland in an article that appeared in Nature (Vol 402, Supplement, December 2, 1999) titled The Future of Evolutionary Developmental Biology recognized a common genome across species. He writes,

"So many examples of [DNA] conservation have now been found that it is no longer considered surprising. We can now state with confidence that most animal phyla possess essentially the same genes, and that some (but not all) of these genes change their developmental roles infrequently in evolution [emphasis added]."

When and where ecological conditions become hospitable, the highly conserved nucleotide sequences of the animal kingdom launch into existence new species, as needed, via the rewiring of developmental patterns. This is the developmental model of evolution proposed by the star larvae hypothesis. Evolution (phylogeny) shares with development (ontogeny) raw materials (a highly conserved set of nucleotides), operating mechanisms (gene regulatory networks), and outputs (highly diverse phenotypes).

Whether we’re talking cells in a body or species in an ecology, phenotypes diversify, or differentiate, from variously regulated but shared genes. Natural selection can cull the herd in an ecology, filtering from the pool genes that lead to reproductive incompetence, just as it can with cells in a body. As philosopher Jerry Fodor summarized it, natural selection can at most tune the piano. It cannot compose the melody.

The role of composer, or at least of conductor, seems to fall to endogenous gene regulatory networks.

But if evolution is an instance of development, then what strange creature is developing?

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