由于对杂合子中的变体的人工选择和针对纯合子中的变体的纯化选择的相互作用,有害等位基因可以处于平衡选择之下。这些多效性变体可以保持中等到高频率,表达杂合子有利性状的优势,而对纯合子有害。对群体和选择强度的影响取决于变体在杂合子和纯合子中的结果。纯合子中表达的有害表型的范围可以从早期致死性到人群中略低的适应度。在这次审查中,我们在平衡选择下探索了一系列致病变异,包括功能丧失变异(即,移码,停止获得的变异)和调节变异(影响基因表达)。我们报告说,有害等位基因通常会影响不同物种的直系同源基因,经常影响类似的特征。最近的发现主要是由于牲畜种群中基因组和表型资源的增加。然而,纯合子中的低频率和有时微妙的影响阻止了这种多效性变体的准确定位,这需要新的策略来发现。发现之后,在平衡选择下有害变体的选择策略正在争论中,由于变体可以导致各种牲畜物种中杂交动物的杂种优势效应,补偿纯种动物的损失。然而,基因辅助选择是降低人群中有害等位基因频率的有用工具,如果需要的话。一起,这篇综述在平衡选择和描述分子的功能后果下标记了各种有害变体,表型,和人口水平,为进一步研究提供资源。
Harmful alleles can be under balancing selection due to an interplay of artificial selection for the variant in heterozygotes and purifying selection against the variant in homozygotes. These pleiotropic variants can remain at moderate to high frequency expressing an advantage for favorable traits in heterozygotes, while harmful in homozygotes. The impact on the population and selection strength depends on the consequence of the variant both in heterozygotes and homozygotes. The deleterious phenotype expressed in homozygotes can range from early lethality to a slightly lower fitness in the population. In this
review, we explore a range of causative variants under balancing selection including loss-of-function variation (i.e., frameshift, stop-gained variants) and regulatory variation (affecting gene expression). We report that harmful alleles often affect orthologous genes in different species, often influencing analogous traits. The recent discoveries are mainly driven by the increasing genomic and phenotypic resources in livestock populations. However, the low frequency and sometimes subtle effects in homozygotes prevent accurate mapping of such pleiotropic variants, which requires novel strategies to discover. After discovery, the selection strategy for deleterious variants under balancing selection is under debate, as variants can contribute to the heterosis effect in crossbred animals in various livestock species, compensating for the loss in purebred animals. Nevertheless, gene-assisted selection is a useful tool to decrease the frequency of the harmful allele in the population, if desired. Together, this
review marks various deleterious variants under balancing selection and describing the functional consequences at the molecular, phenotypic, and population level, providing a resource for further study.