Increased homozygosity due to endogamy results in fitness consequences in a human population

Abstract

Human populations have been shown to differ in their mutation load—the accumulation of mutations in their genomes; the penetrance of these mutations will depend on their recessive, dominant, or additive states. However, most estimates of mutation load are theoretical and have not been associated with evolutionary fitness (i.e., reproductive success). Here, we assess the effect of runs of homozygosity on fitness in a natural fertility population from northern Namibia. As the homozygous fraction of the genome increases, female fertility is significantly reduced. This suggests a multilocus genetic effect on fitness driven by the expression of deleterious recessive alleles. Interestingly, despite a cultural preference for consanguineous marriage in the Himba, we find that such marriages rarely occur between close biological kin.