A scan for positively selected genes in the genomes of humans and chimpanzees

Abstract

Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome also tend to show an elevated tendency for positive selection. We also present polymorphism data from 20 Caucasian Americans and 19 African Americans for the 50 annotated genes showing the strongest evidence for positive selection. The polymorphism analysis further supports the presence of positive selection in these genes by showing an excess of high-frequency derived nonsynonymous mutations.

Figure 1. Distribution of Mutations

The figure shows the number of synonymous and nonsynonymous nucleotide differences in 13,731 human–chimpanzee orthologous gene pairs.

Figure 2. Frequency Spectra

The figure shows the frequency spectra of nonsynonymous (red) and synonymous (black) mutations among the 50 genes showing the strongest evidence for positive selection in the interspecific comparison. Also shown is the expectation from the standard neutral model, expectations from the neutral model taking the protocol used to select the 50 genes into account (see text), and from the prediction of the selection model. On the x-axis is the number of derived allele in a sample of size 30 chromosomes (Count), and on the y-axis is the proportion of sites expected in the sample with a particular frequency.

Figure 3. Power of the Likelihood Ratio Test for Positive Selection

The power is shown as a function of the proportion of the d_N/d_S ratio, and for sequence lengths (n) of 150 and 500 codons. Power is defined as the proportion of tests that are significant at the 5% level. Simulation parameters, including codon frequencies, transition/transversion bias, and divergence times, are equal to the values estimated from the data. Notice the logarithmic x-axis.