Genome patterns of selection and introgression of haplotypes in natural populations of the house mouse (Mus musculus).
Genome patterns of selection and introgression of haplotypes in natural populations of the house mouse (Mus musculus).
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DOI：
10.1371/journal.pgen.1002891
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Tautz D
中科院分区：
文献类型：
--
作者：
Staubach F;Lorenc A;Messer PW;Tang K;Petrov DA;Tautz D
选择的一般参数，如自然种群中正选择的频率和强度或基因渗入的作用，仍然没有得到充分的理解。家鼠（小家鼠）是一个特别适合的模型系统来解决这些问题，因为它有一个明确的历史分裂成亚种和种群，因为广泛的基因组信息是可用的。我们已经使用高密度单核苷酸多态性（SNP）分型阵列，以评估基因组模式的积极选择和渐渗的等位基因在两个自然群体的每个亚种M。M. Acetylticus和M. M.肌肉应用不同的统计程序，我们发现了大量的地区受到明显的选择性扫描，表明频繁的积极选择罕见的等位基因或新的突变。这些区域中的基因包括研究充分的印记基因座（如Plagl 1/Zac 1）、与适应有关的人类基因（如α-淀粉酶基因）或与遗传疾病有关的人类基因（如亨廷顿和帕金）的同源物。两个亚种之间的单倍型匹配揭示了大量的单倍型，这些单倍型显示出来自相应其他亚种的特定群体的渐渗模式，其中至少10%的基因组受到部分或完全渐渗的影响。使用中性模拟进行比较，我们发现，渗入单倍型的大小和比例是不兼容的纯迁移或不完整的谱系排序模型。因此，它似乎渗入单倍型可以上升的频率，由于积极的选择，从而可以有助于适应自然种群的基因组景观。我们的数据支持这一观点，即自然基因组受到复杂的适应过程，包括渗入的单倍型从其他分化的人口或物种在一个更大的规模比以前假设的动物。这意味着在近交系小鼠中发现的一些混合物也可能具有天然来源。尽管有大量证据表明自然种群中存在表型适应，但了解潜在的遗传过程仍然是一个挑战。家鼠已经连续几次在世界上殖民，最近的一次是在人类农业和跨洋航运的传播之后。它们已经适应了许多栖息地和气候，它们的种群为研究适应和积极选择对基因组的影响提供了丰富的机会。通过扫描四个自然种群小鼠的全基因组，我们发现了最近正选择的大量证据，包括已知与人类遗传疾病有关的基因座。出乎意料的是，我们还发现了长期分离的种群之间的高比例基因交换。这一发现支持了这样的观点，即等位基因的杂交和转移可以显着有助于新的遗传物质受到积极的选择。
General parameters of selection, such as the frequency and strength of positive selection in natural populations or the role of introgression, are still insufficiently understood. The house mouse (Mus musculus) is a particularly well-suited model system to approach such questions, since it has a defined history of splits into subspecies and populations and since extensive genome information is available. We have used high-density single-nucleotide polymorphism (SNP) typing arrays to assess genomic patterns of positive selection and introgression of alleles in two natural populations of each of the subspecies M. m. domesticus and M. m. musculus. Applying different statistical procedures, we find a large number of regions subject to apparent selective sweeps, indicating frequent positive selection on rare alleles or novel mutations. Genes in the regions include well-studied imprinted loci (e.g. Plagl1/Zac1), homologues of human genes involved in adaptations (e.g. alpha-amylase genes) or in genetic diseases (e.g. Huntingtin and Parkin). Haplotype matching between the two subspecies reveals a large number of haplotypes that show patterns of introgression from specific populations of the respective other subspecies, with at least 10% of the genome being affected by partial or full introgression. Using neutral simulations for comparison, we find that the size and the fraction of introgressed haplotypes are not compatible with a pure migration or incomplete lineage sorting model. Hence, it appears that introgressed haplotypes can rise in frequency due to positive selection and thus can contribute to the adaptive genomic landscape of natural populations. Our data support the notion that natural genomes are subject to complex adaptive processes, including the introgression of haplotypes from other differentiated populations or species at a larger scale than previously assumed for animals. This implies that some of the admixture found in inbred strains of mice may also have a natural origin. Although there is abundant evidence for phenotypic adaptation in natural populations, it is still a challenge to understand the underlying genetic processes. House mice have colonized the world in several successive waves, the most recent ones in the wake of the spread of human agriculture and trans-oceanic shipping. They have adapted to many habitats and climates, and their populations provide a rich source of opportunities for studying the impact of adaptation and positive selection on the genome. By scanning the whole genome of four natural populations of mice, we detect abundant evidence for recent positive selection, including loci that are known to be involved in genetic diseases in humans. Unexpectedly, we also find a high proportion of gene exchange between populations that have long been separated. This finding supports the notion that hybridization and transfer of alleles can significantly contribute to new genetic material subject to positive selection.
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