Asymmetric and non-uniform evolution of recently duplicated human genes

Abstract

Background: Gene duplications are a source of new genes and protein functions. The innovative role of duplication events makes families of paralogous genes an interesting target for studies in evolutionary biology. Here we study global trends in the evolution of human genes that resulted from recent duplications.

Results: The pressure of negative selection is weaker during a short time immediately after a duplication event. Roughly one fifth of genes in paralogous gene families are evolving asymmetrically: one of the proteins encoded by two closest paralogs accumulates amino acid substitutions significantly faster than its partner. This asymmetry cannot be explained by differences in gene expression levels. In asymmetric gene pairs the number of deleterious mutations is increased in one copy, while decreased in the other copy as compared to genes constituting non-asymmetrically evolving pairs. The asymmetry in the rate of synonymous substitutions is much weaker and not significant.

Conclusions: The increase of negative selection pressure over time after a duplication event seems to be a major trend in the evolution of human paralogous gene families. The observed asymmetry in the evolution of paralogous genes shows that in many cases one of two gene copies remains practically unchanged, while the other accumulates functional mutations. This supports the hypothesis that slowly evolving gene copies preserve their original functions, while fast evolving copies obtain new specificities or functions.

Figure 1

Relationships between gene i, its sister j and cousin k. L_i = (L_[i-j] + L_[i-k] - L_[j-k])/2, where L_i is the individual distance (T, dS or dN) for gene i. L_[i-j] is the distance between gene i and its sister j. L_[i-k] is the distance between gene i and its cousin k. L_[j-k] is the distance between the sister and the cousin of gene i.

Figure 2

Individual dS and dN/dS of genes. Single-exon genes are shown as blue circles, genes with multiple-exons are represented by green triangles. Only genes with individual 0.005 ≤ dS ≤ 0.6 are shown. Linear regression trend lines are provided for single-exon and multiple-exon genes separately (regression coefficients not shown).

Figure 3

Individual dS and individual dN of genes. Single-exon genes are shown as blue circles, genes with multiple-exons are represented by green triangles. Only genes with individual 0.005 ≤ dS ≤ 0.6 are shown. Linear regression trend lines are provided for single-exon and multiple-exon genes separately (regression coefficients not shown).

Figure 4

The average dN/dS for gene families and their average dS. Single-exon genes are shown as blue circles, genes with multiple-exons are represented by green triangles. Only genes with individual 0.005 ≤ dS ≤ 0.6 are shown. Linear regression trend lines are provided for single-exon and multiple-exon genes separately (regression coefficients not shown).

Figure 5

The average dN for gene families and their average dS. Single-exon genes are shown as blue circles, genes with multiple-exons are represented by green triangles. Only genes with individual 0.005 ≤ dS ≤ 0.6 are shown. Linear regression trend lines are provided for single-exon and multiple-exon genes separately (regression coefficients not shown).