Data from: Exploring the mechanisms underlying a heterozygosity-fitness correlation for canine size in the Antarctic fur seal Arctocephalus gazella

Although heterozygosity-fitness correlations (HFCs) are widely reported in the literature, most studies use too few markers to allow the proximate mechanisms to be convincingly resolved. Two competing hypotheses have been proposed: the general effects hypothesis, in which marker heterozygosity correlates with genome-wide heterozygosity and hence the inbreeding coefficient f, and the local effects hypothesis, in which one or more of the markers by chance exhibit associative overdominance. To explore the relative contributions of general and local effects in a free-ranging marine mammal population, we revisited a strong HFC found using nine microsatellite loci for canine tooth size in 84 male Antarctic fur seals Arctocephalus gazella (Hoffman et al. 2010). Increasing the number of markers to 76, we find that heterozygosity is uncorrelated across markers, indicating that inbred individuals are rare or absent. Similarly, while the HFC based on overall heterozygosity is lost, stochastic simulations indicate that when an HFC is due to inbreeding depression, increasing marker number effectively invariably strengthens the HFC. Together these observations argue strongly that the original HFC was not due to inbreeding depression. In contrast, a subset of markers show individually significant effects, and these are non-randomly distributed across the marker panel, being preferentially associated with markers cloned from other species. Using BLAST searches, we were able to locate 94% of loci to unique locations in the dog genome, but the local genes are functionally diverse, and the majority cannot be linked directly to growth. Our results suggest that inbreeding depression contributes little if at all to the relationship between heterozygosity and tooth size, but that instead the primary mechanism involves associative overdominance. These findings contribute to a growing body of evidence suggesting that general effects are likely to be uncommon in natural populations

尽管杂合度-适合度相关性（heterozygosity-fitness correlations, HFCs）在学术文献中被广泛报道，但多数研究采用的标记数量过少，难以令人信服地解析其近因机制。目前已提出两种相互对立的假说：其一为普遍效应假说（general effects hypothesis），即标记杂合度与全基因组杂合度相关，进而与近交系数f相关联；其二为局部效应假说（local effects hypothesis），即一个或多个标记偶然表现出关联超显性（associative overdominance）。为探究自由活动的海洋哺乳动物种群中普遍效应与局部效应的相对贡献，我们重新分析了一项既往研究结果：该研究在84只雄性南极海狗（Arctocephalus gazella）中，利用9个微卫星位点（microsatellite loci）发现了犬齿大小与HFC的显著关联（Hoffman等，2010）。本次研究将标记数量提升至76个，结果发现不同标记间的杂合度并无相关性，这表明近交个体极为罕见甚至不存在。类似地，基于整体杂合度的HFC已不复存在；而随机模拟结果显示，若HFC由近交衰退（inbreeding depression）导致，增加标记数量通常会持续增强该HFC。综合上述观察结果，我们有充分依据认为，最初发现的HFC并非由近交衰退所致。与之相反，部分标记单独表现出显著效应，且这些标记在整个标记组中并非随机分布，而是优先富集自其他物种克隆得到的标记。通过BLAST搜索，我们成功将94%的位点定位到犬基因组的唯一位置，但这些局部基因的功能具有多样性，多数无法直接与生长相关联。我们的研究结果表明，近交衰退对杂合度与犬齿大小之间的关联几乎没有贡献，其核心机制实为关联超显性。上述发现为日益增多的相关证据链补充了新的支撑，即普遍效应在自然种群中可能并不常见。