Lactase haplotype diversity in the Old World.

Area of Science:

• Human genetics
• Population genetics
• Evolutionary biology

Background:

• Lactase persistence, the ability to digest milk into adulthood, varies geographically.
• This trait is most common in northern Europeans and certain African and Arabian nomadic groups with a history of milk consumption.
• Agricultural pastoralism, emerging ~9,000 years ago, likely influenced lactase persistence frequencies.

Purpose of the Study:

• To investigate the genetic basis of lactase persistence/nonpersistence polymorphism.
• To analyze the distribution and diversity of 11-site lactase gene haplotypes across 11 human populations.
• To evaluate the roles of genetic drift and selection in shaping haplotype frequencies.

Main Methods:

• Studied 11-site haplotypes in 1,338 chromosomes from 11 diverse populations.
• Utilized allele-specific PCR for analyzing recombinant haplotypes.
• Constructed a haplotype network using chimpanzee sequence data to infer evolutionary relationships.

Main Results:

• Haplotype diversity arose from mutations and recombination.
• Four common haplotypes (A, B, C, U) showed distinct global distributions.
• Haplotype A, linked to lactase persistence, is frequent only in northern Europeans; haplotype U is rare in Indo-European populations.
• Sub-Saharan Africans exhibited greater haplotype diversity than non-Africans, supporting the "Out of Africa" model.

Conclusions:

• Genetic drift played a significant role in non-African haplotype diversity.
• Recent directional selection in northern Europeans favored the lactase persistence-associated haplotype.