Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.
J Hered. 2010 Sep-Oct;101(5):539-52. doi: 10.1093/jhered/esq046. Epub 2010 May 9.
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 effect hypothesis, in which marker heterozygosity correlates with genome-wide heterozygosity and hence the inbreeding coefficient f, and the local effect 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 9 microsatellite loci for canine tooth size in 84 male Antarctic fur seals Arctocephalus gazella (Hoffman JI, Hanson N, Forcada J, Trathan PN, Amos W. 2010. Getting long in the tooth: a strong positive correlation between canine size and heterozygosity in the Antarctic fur seal Arctocephalus gazella. J Hered.). Increasing the number of markers to 76, we find that heterozygosity is uncorrelated across loci, 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 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 nonrandomly distributed across the marker panel, being preferentially associated with markers cloned from other species. Using basic alignment search tool 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.
虽然杂种优势与适合度相关（HFC）在文献中被广泛报道，但大多数研究使用的标记太少，无法令人信服地确定其潜在机制。目前有两种相互竞争的假说：一般效应假说，其中标记杂合度与全基因组杂合度相关，因此与近交系数 f 相关；局部效应假说，其中一个或多个标记偶然表现出关联超显性。为了在自由放养的海洋哺乳动物种群中探索一般和局部效应的相对贡献，我们重新研究了一项使用 9 个微卫星标记对 84 只雄性南极软毛海豹犬齿大小的强烈 HFC（Hoffman JI，Hanson N，Forcada J，Trathan PN，Amos W. 2010. 变得更长：南极软毛海豹犬齿大小与杂合度之间的强烈正相关关系。J Hered.）。通过增加到 76 个标记，我们发现等位基因在不同位点之间没有相关性，这表明近交个体很少或不存在。同样，尽管基于整体杂合度的 HFC 消失了，但随机模拟表明，当 HFC 是由于近交衰退引起时，增加标记数量总是会增强 HFC。这些观察结果强烈表明，原始 HFC 不是由于近交衰退引起的。相比之下，一部分标记显示出个体显著的效应，并且这些效应在标记面板中是非随机分布的，优先与从其他物种克隆的标记相关。通过基本的比对搜索工具搜索，我们能够将 94%的位点定位到犬基因组中的独特位置，但局部基因功能多样，大多数基因不能直接与生长相关。我们的结果表明，近交衰退对杂合度与牙齿大小之间的关系几乎没有贡献，而主要机制涉及关联超显性。这些发现有助于越来越多的证据表明，一般效应在自然种群中可能不常见。
