Reassessing the Evolutionary History of the 17q21 Inversion Polymorphism.

Area of Science:

• Human genetics
• Population genetics
• Evolutionary biology

Background:

• Chromosome 17q21 harbors a polymorphic inversion with two main haplotype families (H1 and H2).
• The evolutionary spread and selective pressures of the H2 inversion lineage in humans are not fully understood.
• A selective advantage has been hypothesized for certain H2 subtypes.

Purpose of the Study:

• To investigate the distribution and diversity of H2 haplotypes in previously underrepresented African populations.
• To explore the evolutionary history and potential selective forces driving the H2 inversion.

Main Methods:

• Genotyping of a large African cohort using a custom array with H2-specific single nucleotide polymorphisms.
• Analysis of haplotype distribution, frequency, and genetic relatedness.

Main Results:

• H2 haplotypes exhibit a patchy distribution across Africa, with higher frequencies of inverted subtypes in North African populations compared to Sub-Saharan groups.
• North African H2 haplotypes demonstrate closer genetic relationships to non-African chromosomes, suggesting recent divergence.
• Increased diversity within the H2 family was observed, challenging the notion of a uniform strong selective sweep.

Conclusions:

• The evolutionary history of the 17q21 inversion is more complex than previously assumed.
• North African populations may offer insights into recent human population movements and admixture.
• The findings necessitate a re-evaluation of selective sweep hypotheses at this locus.