The 8p23 Inversion polymorphism determines local recombination heterogeneity across human populations

Abstract

For decades, chromosomal inversions have been regarded as fascinating evolutionary elements as they are expected to suppress recombination between chromosomes with opposite orientations, leading to the accumulation of genetic differences between the twoconfigurations over time.Here,makinguseofpublicly availablepopulationgenotypedata for the largestpolymorphic inversion in thehumangenome(8p23-inv),weassessedwhether this inhibitory effect of inversion rearrangements ledtosignificantdifferences in the recombination landscape of two homologous DNA segments, with opposite orientation. Our analysis revealed that the accumulation of genetic differentiation is positively correlated with the variation in recombination profiles. The observed recombination dissimilarity between inversion types is consistent across all populations analyzed and surpasses the effects of geographic structure, suggesting that both structures (orientations) have been evolving independently over an extended period of time, despite being subjected tothe very samedemographichistory.Aside this mainly independent evolution,wealso identified a short segment (350 kb, <10% of the whole inversion) in the central region of the inversion where the genetic divergence between the two structural haplotypes is diminished. Although it is difficult to demonstrate it, this could be due to gene flow (possibly via double-crossing over events), which is consistent with the higher recombination rates surrounding this segment. This study demonstrates for the first time that chromosomal inversions influence the recombination landscape at afine-scale andhighlights the role of these rearrangements as drivers of genome evolution. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.