Does heterozygosity estimate inbreeding in real populations?
Does heterozygosity estimate inbreeding in real populations?
复制标题
DOI：
10.1111/j.1365-294x.2004.02318.x
复制
发表时间：
2004-10-01
影响因子：
4.9
通讯作者：
Coulson, T
中科院分区：
文献类型：
--
作者：
Balloux, F;Amos, W;Coulson, T
最近的许多研究报告称，少数几个明显中性的微卫星标记的个体杂合性与健康的关键组成部分相关，大多数研究认为近亲繁殖抑制可能是潜在的机制。隐含的假设是，只使用10个左右的标记就可以可靠地估计一个人的近亲繁殖系数，但这个假设的有效性尚不清楚。因此，我们使用基于个体的模拟来检查杂合性和近亲交配可能相关的条件。我们的结果表明，发生这种情况的参数空间令人惊讶地狭窄，要求近亲交配事件既频繁又严重，例如，通过自交、强大的种群结构和/或高水平的一夫多妻制。即便如此，只有当大量的基因座(接近200个)被用来估计杂合性时，这种相关性才会很强。对于大多数研究中使用的少数标记，只有在我们观察到的最极端的情况下，相关性才可能变得可能，即20个人的20个Deme加上强大的一夫多妻制。这一发现得到了一个观察的支持，即杂合性只在个人内部的标记之间存在弱相关性，即使在一个由400个标记组成的数据集中也是如此，这些标记在不同的人类群体中分类，其中一些人倾向于近亲婚姻。如果杂合度和近交系数通常是不相关的，那么杂合度-适合度相关性可能与近交抑郁没有什么关系。相反，人们需要调用所使用的标记和经历平衡选择的一个或多个基因(S)之间的偶然联系。不幸的是，这两种解释都有点不符合当前的理解。如果近亲交配是主要的机制，那么我们的模拟表明，近亲交配将比对大多数现实种群的预测要普遍得多。相反，如果杂种优势提供了答案，则需要比通常假设的更多具有主要适合度效应的多态和更高水平的连锁不平衡。
Many recent studies report that individual heterozygosity at a handful of apparently neutral microsatellite markers is correlated with key components of fitness, with most studies invoking inbreeding depression as the likely underlying mechanism. The implicit assumption is that an individual's inbreeding coefficient can be estimated reliably using only 10 or so markers, but the validity of this assumption is unclear. Consequently, we have used individual-based simulations to examine the conditions under which heterozygosity and inbreeding are likely to be correlated. Our results indicate that the parameter space in which this occurs is surprisingly narrow, requiring that inbreeding events are both frequent and severe, for example, through selfing, strong population structure and/or high levels of polygyny. Even then, the correlations are strong only when large numbers of loci (similar to200) can be deployed to estimate heterozygosity. With the handful of markers used in most studies, correlations only become likely under the most extreme scenario we looked at, namely 20 demes of 20 individuals coupled with strong polygyny. This finding is supported by the observation that heterozygosity is only weakly correlated among markers within an individual, even in a dataset comprising 400 markers typed in diverse human populations, some of which favour consanguineous marriages. If heterozygosity and inbreeding coefficient are generally uncorrelated, then heterozygosity-fitness correlations probably have little to do with inbreeding depression. Instead, one would need to invoke chance linkage between the markers used and one or more gene(s) experiencing balancing selection. Unfortunately, both explanations sit somewhat uncomfortably with current understanding. If inbreeding is the dominant mechanism, then our simulations indicate that consanguineous mating would have to be vastly more common than is predicted for most realistic populations. Conversely, if heterosis provides the answer, there need to be many more polymorphisms with major fitness effects and higher levels of linkage disequilibrium than are generally assumed.