Evidence of convergent evolution in humans and macaques supports an adaptive role for copy number variation of the β-defensin-2 gene.

β-defensins are a family of important peptides of innate immunity, involved in host defense, immunomodulation, reproduction, and pigmentation. Genes encoding β-defensins show evidence of birth-and-death evolution, adaptation by amino acid sequence changes, and extensive copy number variation (CNV) within humans and other species. The role of CNV in the adaptation of β-defensins to new functions remains unclear, as does the adaptive role of CNV in general. Here, we fine-map CNV of a cluster of β-defensins in humans and rhesus macaques. Remarkably, we found that the structure of the CNV is different between primates, with distinct mutational origins and CNV boundaries defined by retroviral long terminal repeat elements. Although the human β-defensin CNV region is 322 kb and encompasses several genes, including β-defensins, a long noncoding RNA gene, and testes-specific zinc-finger transcription factors, the orthologous region in the rhesus macaque shows CNV of a 20-kb region, containing only a single gene, the ortholog of the human β-defensin-2 gene. Despite its independent origins, the range of gene copy numbers in the rhesus macaque is similar to humans. In addition, the rhesus macaque gene has been subject to divergent positive selection at the amino acid level following its initial duplication event between 3 and 9.5 Ma, suggesting adaptation of this gene as the macaque successfully colonized novel environments outside Africa. Therefore, the molecular phenotype of β-defensin-2 CNV has undergone convergent evolution, and this gene shows evidence of adaptation at the amino acid level in rhesus macaques.