Accelerated rate of gene gain and loss in primates

Abstract

The molecular changes responsible for the evolution of modern humans have primarily been discussed in terms of individual nucleotide substitutions in regulatory or protein coding sequences. However, rates of nucleotide substitution are slowed in primates, and thus humans and chimpanzees are highly similar at the nucleotide level. We find that a third source of molecular evolution, gene gain and loss, is accelerated in primates relative to other mammals. Using a novel method that allows estimation of rate heterogeneity among lineages, we find that the rate of gene turnover in humans is more than 2.5 times faster than in other mammals and may be due to both mutational and selective forces. By reconciling the gene trees for all of the gene families included in the analysis, we are able to independently verify the numbers of inferred duplications. We also use two methods based on the genome assembly of rhesus macaque to further verify our results. Our analyses identify several gene families that have expanded or contracted more rapidly than is expected even after accounting for an overall rate acceleration in primates, including brain-related families that have more than doubled in size in humans. Many of the families showing large expansions also show evidence for positive selection on their nucleotide sequences, suggesting that selection has been important in shaping copy-number differences among mammals. These findings may help explain why humans and chimpanzees show high similarity between orthologous nucleotides yet great morphological and behavioral differences.

Figure 1.—

Rates of gene gain and loss across the mammals. The species tree of the six mammalian genomes considered is shown, shaded according to the estimated rates of gene gain and loss.

Figure 2.—

Rapidly evolving gene families. Individual families showing significantly accelerated rates of evolution along the human, chimpanzee, and macaque lineages are shown. Each row is a single gene family, with the relative rate of evolution along the human (red), chimpanzee (green), and macaque (blue) lineages given by the width of the colored bars. The size of the family in each of the three species is shown to the right; italicized numbers indicate significance in that lineage.

Figure 3.—

Gene tree for centaurin gamma. The relationships among the members of the centaurin gamma gene family are shown, including gene copies from human, chimpanzee, macaque, mouse, and rat. The numbers for each protein correspond to Ensembl protein identification numbers.