"Transcriptomic insights into genetic diversity of protein-coding genes in X. laevis"

by Savova Virginia, Pearl EJ, Boke E, Nag A, Adzhubei I, Horb ME, Peshkin Leonid.

Keywords:
systems embryology | protein economy in development | predictive modeling | mass action kinetics | protein synthesis rates | protein stability | protein degradation rates

Abstract:
We characterize the genetic diversity of Xenopus laevis strains using RNA-seq data and allele-specific analysis. This data provides a catalogue of coding variation, which can be used for improving the genomic sequence, as well as for better sequence alignment, probe design, and proteomic analysis. In addition, we paint a broad picture of the genetic landscape of the species by functionally annotating different classes of mutations with a well-established prediction tool (PolyPhen-2). Further, we specifically compare the variation in the progeny of four crosses: inbred genomic (J)-strain, outbred albino (B)-strain, and two hybrid crosses of J and B strains. We identify a subset of mutations specific to the B strain, which allows us to investigate the selection pressures affecting duplicated genes in this allotetraploid. From these crosses we find the ratio of non-synonymous to synonymous mutations is lower in duplicated genes, which suggests that they are under greater purifying selection. Surprisingly, we also find that function-altering ("damaging") mutations constitute a greater fraction of the non-synonymous variants in this group, which suggests a role for subfunctionalization in coding variation affecting duplicated genes.

Summary:
Where do new genes come from in evolution ? A leading theory has it, when an existing gene gets duplicated, new copy is "free to evolve" since another copy is bearing the weight of responsibility to perform the original function. If so, for genes which have a "spare copy" we should see a higher rate of evolution. However it has been noticed a while ago that situation is exactly the opposite -- genes which have a copy are more, not less conserved. In a new study, Savova et al. refine this argument using species of frogs in which roughly half of all the genes have a spare -- "it depends on how you count things". Specifically, since not every amino-acid change in a protein results in a change of protein structure and function, counting only changes that matter, substantially alters the statistics of substitutions and supports the original theory, known as "sub-functionalization". In other words, when paired up genes do change, a change is more likely to alter resulting protein so it might introduce a novelty !

PMID: 28283406

Where do new genes come from in evolution ?