Origin and evolution of the c.844_845ins68/c.833T>C mutations within the cystathionine β-synthase gene in great apes

The c.[833C; 844_845ins68] is a common haplotype of the human cystathionine β-synthase gene among healthy individuals. This polymorphism (5–40% allelic frequency in different populations) consists of the c.844_845ins68 insertion that segregates in cis with the pathogenic c.833T>C substitution (p.I278T). Through genotyping of primates, we have found that gorillas, chimpanzees and bonobos are homozygous for the 68 bp insertion, c.844_845ins68. In gorillas and bonobos, the c.844_845ins68 lesion segregates in cis with the wild-type c.833T variant, whilst chimpanzees present the human haplotype. These genetic evidences suggest that the origin of the 68 bp insertion might be dated back to 6–8 million years ago, and that the c.833T>C substitution occurred within the allele carrying the insertion. The evolutionary conservation of this peculiar haplotype supports the hypothesis of its protective effects against cardiovascular diseases.