Contrasting histories of G6PD molecular evolution and malarial resistance in humans and chimpanzees

Area of Science:

• Evolutionary genetics
• Primate genomics
• Molecular anthropology

Background:

• Mutations in the glucose-6-phosphate dehydrogenase (G6PD) gene are linked to human blood disorders and malaria resistance.
• Population genetic analyses suggest G6PD mutations have undergone recent positive selection in humans, particularly in malaria-endemic regions.

Purpose of the Study:

• To investigate G6PD nucleotide sequence variation in chimpanzees and other nonhuman primates.
• To compare G6PD patterns in primates with humans to determine if malaria-impacted primates show similar signs of positive selection.
• To understand the evolutionary history of G6PD and its role in primate adaptation.

Main Methods:

• DNA sequencing of a 5.2-kb region of the G6PD locus in 56 chimpanzees and 7 other primate species.
• Analysis of nucleotide sequence variation, including amino acid variants.
• Comparative genomic analysis to assess patterns of polymorphism and divergence.

Main Results:

• Chimpanzees exhibit several amino acid variants in the G6PD gene.
• The overall G6PD pattern in chimpanzees and other primates (Old and New World) is consistent with purifying selection and strong functional constraint dating back millions of years.
• No evidence of recent positive selection at the G6PD locus was found in the studied nonhuman primate populations.

Conclusions:

• The unique signature of recent positive selection at the G6PD locus observed in humans is not present in chimpanzees or other nonhuman primates.
• The G6PD gene has been under strong functional constraint for at least 30-40 million years across primate evolution.
• Human G6PD evolution, particularly its recent adaptation related to malaria, appears distinct from that of other primates.