Positive selection, relaxation, and acceleration in the evolution of the human and chimp genome

Abstract

For years evolutionary biologists have been interested in searching for the genetic bases underlying humanness. Recent efforts at a large or a complete genomic scale have been conducted to search for positively selected genes in human and in chimp. However, recently developed methods allowing for a more sensitive and controlled approach in the detection of positive selection can be employed. Here, using 13,198 genes, we have deduced the sets of genes involved in rate acceleration, positive selection, and relaxation of selective constraints in human, in chimp, and in their ancestral lineage since the divergence from murids. Significant deviations from the strict molecular clock were observed in 469 human and in 651 chimp genes. The more stringent branch-site test of positive selection detected 108 human and 577 chimp positively selected genes. An important proportion of the positively selected genes did not show a significant acceleration in rates, and similarly, many of the accelerated genes did not show significant signals of positive selection. Functional differentiation of genes under rate acceleration, positive selection, and relaxation was not statistically significant between human and chimp with the exception of terms related to G-protein coupled receptors and sensory perception. Both of these were over-represented under relaxation in human in relation to chimp. Comparing differences between derived and ancestral lineages, a more conspicuous change in trends seems to have favored positive selection in the human lineage. Since most of the positively selected genes are different under the same functional categories between these species, we suggest that the individual roles of the alternative positively selected genes may be an important factor underlying biological differences between these species.

Figure 1. PS and Rates of Evolution

A minor proportion of genes with Ka/Ks > 1 match events of PS in human and in chimp (red circles). Many of the genes with Ka/Ks < 1 show evidence of PS (blue circles). Genes with Ka/Ks > 1 without evidence of PS (black asterisks) fall mostly under molecular clock conditions for nonsynonymous changes (circles below the broken red line). Most of the genes without evidence of PS and Ka/Ks < 1 (grey circles) are scattered below the boundary limiting molecular clock like behavior and are observed at dKa < 0.0006 when molecular clock conditions are not fulfilled. Genes outside of clock conditions and dKa > 0.0006 coincide mostly with events of PS in both of the species (red and blue circles above the broken line). dKa and rKa as defined in Table 1.

Figure 2. Phylogenetic Distribution of PSG under Tests I and II

(A) The differential distribution of genes along tree branches, suggests a different pattern of occurrence of PS (Test II) and RSC (Test I) in derived and ancestral lineages. Numbers in red represent the total number of genes detected in each test after correcting for multiple testing. Numbers in black are common orthologous genes observed between lineages. Numbers in blue are genes observed in both tests. (B) The phylogenetic distribution of four representative GO categories is shown in human, in chimp, and in the ancestral lineage as depicted in the tree defined above. Numbers correspond to the percentage representation of genes under PS and RSC for each term out of the total number of genes with GO annotation. Filled circles show significant (red) and nonsignificant (grey) differences in the comparisons (see text for a detailed explanation).

Figure 3. Ancestral and Derived Trends in Adaptation and RSC

Differences in GO term representation between the sets of the derived and the ancestral lineages (H-AH, human versus ancestral lineage; CH-AH, chimp versus ancestral lineage) are plotted against each other using genes exclusively observed in Test I (RSC) and Test II (PS). Each quadrant represents a particular evolutionary scenario increasing or decreasing in GO representation for each of the lineages after speciation. Terms showing a difference in representation between H-AH and CH-AH >10% were labeled in red: G-coupled protein receptor was found in both Test I (14.32%) and Test II (12.89%), and sensory perception (11.03%) and cellular protein metabolism (−12.34%) in Test II. Only the terms common to all lineages are shown.