Meeks Gillian L, Scelza Brooke, Kichula Katherine M, Berevoescu Catrinel, Hardy Kristin, Farias Ticiana D J, Harrison Genelle F, Pollock Nicholas R, Font-Porterias Neus, Prall Sean, Norman Paul J, Henn Brenna M
Graduate Program in Integrative Genetics and Genomics, University of California Davis, Davis, CA, USA.
Indicates co-authorship position.
bioRxiv. 2025 May 8:2025.05.06.652536. doi: 10.1101/2025.05.06.652536.
Evidence for disassortative mating based on the human-specific MHC, i.e. HLA, is equivocal. Initial evidence for disassortative HLA-pairing in the European-descent Hutterites has tended not to replicate in other populations. Recent studies, rather, reflect assortative mating associated with cosmopolitan population structure. Although their configuration is more relevant to the majority of human evolutionary history, few small-scale, endogamous populations have been examined. Here, we test whether the extent of HLA dissimilarity between individuals influences mate choice by contrasting chosen partnerships (both "love" marriages and informal partnerships) with arranged partnerships among the Himba, an endogamous and formerly natural fertility group living in northern Namibia. With targeted sequencing we typed eight classical HLA genes for n=366 individuals and recorded self-reported partnership types and informal partnerships discovered through shared biological offspring. Across 249 known partnerships, we find no difference in HLA dissimilarity between chosen and arranged partnerships and no effect of the two partnership types that differs from a random, background distribution of partnerships. We also looked directly for fitness benefits of the potential offspring genotypes by testing HLA-based pathogen binding affinities, but also found no difference between arranged and chosen partners and no effects that differed from random partners. It is possible that due to high background HLA diversity in the Himba, most unrelated individuals in the population are sufficiently dissimilar at the HLA that there are few fitness benefits to offspring by maximizing mate dissimilarity. We do find, however, extensive haplotype sharing at the HLA region, suggestive of recent positive selection. Episodes of fluctuating positive selection may be a more important driver in maintenance of HLA polymorphism than disassortative mating.
基于人类特有的主要组织相容性复合体(即HLA)的异系交配证据并不明确。欧洲裔哈特派中HLA配对呈异系的初步证据在其他人群中往往无法重现。相反,近期研究反映出与世界性种群结构相关的同系交配。尽管其结构与大多数人类进化史更为相关,但很少有小规模的、近亲通婚的人群被研究过。在此,我们通过对比纳米比亚北部一个近亲通婚且曾保持自然生育的群体——辛巴族中自由选择的伴侣关系(包括“恋爱”婚姻和非正式伴侣关系)与包办婚姻,来检验个体间HLA的差异程度是否会影响配偶选择。通过靶向测序,我们对366名个体的8个经典HLA基因进行了分型,并记录了自我报告的伴侣关系类型以及通过共同生育的后代发现的非正式伴侣关系。在249种已知的伴侣关系中,我们发现自由选择的伴侣关系和包办婚姻在HLA差异上没有区别,并且这两种伴侣关系类型与随机的、背景性的伴侣关系分布相比也没有不同影响。我们还通过测试基于HLA的病原体结合亲和力,直接寻找潜在后代基因型的适应性益处,但同样发现包办婚姻和自由选择的伴侣之间没有差异,且与随机伴侣相比也没有不同影响。有可能由于辛巴族中HLA背景多样性较高,该群体中大多数无亲缘关系的个体在HLA上差异足够大,以至于通过最大化配偶差异对后代几乎没有适应性益处。然而,我们确实在HLA区域发现了广泛的单倍型共享,这表明近期存在正选择。波动的正选择事件可能比异系交配在维持HLA多态性方面是一个更重要的驱动因素。