Origins and impact of constraints in evolution of gene families

Abstract

Recent investigations of high-throughput genomic and phenomic data have uncovered a variety of significant but relatively weak correlations between a gene’s functional and evolutionary characteristics. In particular, essential genes and genes with paralogs have a slight propensity to evolve more slowly than nonessential genes and singletons, respectively. However, given the weakness and multiplicity of these associations, their biological relevance remains uncertain. Here, we show that existence of an essential paralog can be used as a specific and strong gauge of selection. We partition gene families in several genomes into two classes: those that include at least one essential gene (E-families) and those without essential genes (N-families). We find that weaker purifying selection causes N-families to evolve in a more dynamic regime with higher rates both of duplicate fixation and pseudogenization. Because genes in E-families are subject to significantly stronger purifying selection than those in N-families, they survive longer and exhibit greater sequence divergence. Longer average survival time also allows for divergence of upstream regulatory regions, resulting in change of transcriptional context among paralogs in E-families. These findings are compatible with differential division of ancestral functions (subfunctionalization) or emergence of novel functions (neofunctionalization) being the prevalent modes of evolution of paralogs in E-families as opposed to pseudogenization (nonfunctionalization), which is the typical fate of paralogs in N-families. Unlike other characteristics of genes, such as essentiality, existence of paralogs, or expression level, membership in an E-family or an N-family strongly correlates with the level of selection and appears to be a major determinant of a gene’s evolutionary fate.

Ancestral whole-genome duplication in the marine chelicerate horseshoe crabs

“…Transcription of a pseudogenised representative of the Hox gene ftz in T. tridentatus can be observed in the RT-PCR-based assays of several independent individuals (Figure 6b, Supplementary File 1). Whether other xiphosuran Hox pseudogenes are transcribed is unknown, but this example suggests the complete 'silencing' of pseudogenes may take millions of years after a WGD event, allowing sufficient time for extensive remodelling of regulatory mechanisms (Shakhnovich & Koonin, 2006). Birth and death rates for pseudogenes vary from species to species (Podlaha and Zhang, 2010) and the rates can be heightened by high neutral mutation rate, as observed in mouse (Waterston et al, 2002), or by high genomic deletion rates as seen in the fly (Petrov et al, 1996(Petrov et al, , 1998.…”

Natural Diversity in Flowering Responses of Arabidopsis thaliana Caused by Variation in a Tandem Gene Array

“…Gene duplication leads to redundancy, which relaxes selection pressure and thereby creates a substrate for functional evolution (Gu and Gu 2003;Shakhnovich and Koonin 2006;Wagner 2008). Due to redundancy, the capacity to sustain nonlethal mutations is enhanced in gene families compared to singleton genes (Clark et al 2007;Armisen et al 2008).…”

Improvisation in evolution of genes and genomes: whose structure is it anyway?

“…One of the interesting findings presented by Shakhnovich and Koonin [34] was that paralogs that were under evolutionary pressure were able to diverge farther not only in protein sequence but also in their regulatory regions as well. The same patterns were observed in drosophila as well with a positive correlation between sequence divergence and expression [39,40].…”

“…However, it was not entirely clear whether genes that were conserved for other reasons duplicated more often or if conserved genes had lower death rates and higher retention rates [38]. As a way of reconciling the two scenarios, Shakhnovich and Koonin showed that while duplication rates were largely independent of the strength of selection on the duplicates, retention of paralogs was indeed much higher for more conserved genes [34]. In the same paper, the authors show that longer retention of duplicates allows gene families under strong selection to explore more sequence space and diverge farther.…”

“…However, the role of designability in constraining evolution of duplicates and sequence divergence is under debate [31][32][33]. On the other hand, sequence neighborhood has been shown to affect evolutionary dynamics not only of proteins [30][31][32][33][34], but also of small collections of proteins e.g. viruses.…”