Evolutionary significance of gene expression divergence

Abstract

Recent large-scale studies of evolutionary changes in gene expression among mammalian species have led to the proposal that gene expression divergence may be neutral with respect to organismic fitness. Here, we employ a comparative analysis of mammalian gene sequence divergence and gene expression divergence to test the hypothesis that the evolution of gene expression is predominantly neutral. Two models of neutral gene expression evolution are considered: 1-purely neutral evolution (i.e., no selective constraint) of gene expression levels and patterns and 2-neutral evolution accompanied by selective constraint. With respect to purely neutral evolution, levels of change in gene expression between human-mouse orthologs are correlated with levels of gene sequence divergence that are determined largely by purifying selection. In contrast, evolutionary changes of tissue-specific gene expression profiles do not show such a correlation with sequence divergence. However, divergence of both gene expression levels and profiles are significantly lower for orthologous human-mouse gene pairs than for pairs of randomly chosen human and mouse genes. These data clearly point to the action of selective constraint on gene expression divergence and are inconsistent with the purely neutral model; however, there is likely to be a neutral component in evolution of gene expression, particularly, in tissues where the expression of a given gene is low and functionally irrelevant. The model of neutral evolution with selective constraint predicts a regular, clock-like accumulation of gene expression divergence. However, relative rate tests of the divergence among human-mouse-rat orthologous gene sets reveal clock-like evolution for gene sequence divergence, and to a lesser extent for gene expression level divergence, but not for the divergence of tissue-specific gene expression profiles. Taken together, these results indicate that gene expression divergence is subject to the effects of purifying selective constraint and suggest that it might also be substantially influenced by positive Darwinian selection.

Comparative Network Analysis Reveals That Tissue Specificity and Gene Function Are Important Factors Influencing the Mode of Expression Evolution in Arabidopsis and Rice

“…Similarly, after comparison of expression similarity with coding sequences for more than 10,000 human-mouse orthologs, no strong correlation between expression and sequence evolution was found in mammals (Liao and Zhang, 2006). Although contradictory conclusions have been drawn in different species (Makova and Li, 2003;Jordan et al, 2005;Lemos et al, 2005;Liao and Zhang, 2006;Sartor et al, 2006), also in yeast no evidence has been found for a strong correlation between these two modes of gene evolution (Tirosh and Barkai, 2008).…”

Tissue-driven hypothesis of genomic evolution and sequence-expression correlations

“…A basic assumption of the tissue-driven hypothesis is that genome evolves largely under functional constraints maintained by stabilizing selections at levels from cell physiology to development. In some evolutionary lineages, episodic adaptive selection may happen either in expression pattern or in protein function (9,21,(26)(27)(28)(29). For instance, hundreds of genes (Ϸ2% human genes) showed dramatic brain-specific expression shifts in the human lineage (3,4,26,27).…”

“…A good example is from the analyses of refs 3 and 4, implying adaptive expression shifts of some genes in the human brain. However, the opposite view remains (9,21), arguing that expression divergence was mainly driven by natural selection.…”

Constraint and turnover in sex-biased gene expression in the genus Drosophila

“…Quadruplicate replicates within each species were used at a time of 0 million years. expression should have variable effects, owing to underlying mutations in transcription factors, cis-regulatory sites and posttranscriptional regulators, and the resulting variance will be subject to drift and selection 2,3,5,13,[16][17][18] . We were able to distinguish expression differences between species well enough to show a linear relationship with time at the full-transcriptome level, but does this apply to individual genes?…”