Population Genomic Analysis of a Pitviper Reveals Microevolutionary Forces Underlying Venom Chemistry.

Population Genomic Analysis of a Pitviper Reveals Microevolutionary Forces Underlying Venom Chemistry.
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DOI:
10.1093/gbe/evx199
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发表时间:
2017-10-01
影响因子:
3.3
通讯作者:
Mikheyev AS
Mikheyev AS
中科院分区:
生物学2区
文献类型:
--
作者:
Aird SD;Arora J;Barua A;Qiu L;Terada K;Mikheyev AS

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毒液是已知的最具生物活性的分泌物之一,人们普遍认为毒液是在极端的积极选择下进化而来的。然而,许多毒液基因家族经历了重复,并且通常以大大超过大多数猎物物种的LD50的剂量部署,这应该会降低正选择的强度。在这里,我们使用由快速进化的蛋白质配方组成的蛇毒来对比这些选择机制。尽管数十年的广泛研究发现,蛇毒蛋白受到强烈的正向选择的影响,但漂移的更大作用一直是假设的,但从未得到证实。利用从头基因组测序、种群基因组学、转录组学和蛋白质组学的结合,我们比较了pitviper (Protobothrops mucrosquamatus)的两种进化模式。通过在McDonald-Kreitman-type框架中划分选择约束和适应性进化,我们发现了对两种假设的支持:与基因组中的其他基因相比,毒液蛋白确实经历了更强的正向选择和更低的选择约束。此外,选择的强度可能受到表达水平的调节,更丰富的蛋白质经历更弱的选择约束,导致更多有害突变的积累。这些发现表明,蛇毒通过适应性和中性机制的结合进化,这两种机制都解释了它们异常高的分子进化速度。除了在短期内优化毒液功效的正选择外,放宽对有害突变的选择限制可以导致单个蛋白质的更快周转,并有可能探索更大的毒液表型空间。
Venoms are among the most biologically active secretions known, and are commonly believed to evolve under extreme positive selection. Many venom gene families, however, have undergone duplication, and are often deployed in doses vastly exceeding the LD50 for most prey species, which should reduce the strength of positive selection. Here, we contrast these selective regimes using snake venoms, which consist of rapidly evolving protein formulations. Though decades of extensive studies have found that snake venom proteins are subject to strong positive selection, the greater action of drift has been hypothesized, but never tested. Using a combination of de novo genome sequencing, population genomics, transcriptomics, and proteomics, we compare the two modes of evolution in the pitviper, Protobothrops mucrosquamatus. By partitioning selective constraints and adaptive evolution in a McDonald–Kreitman-type framework, we find support for both hypotheses: venom proteins indeed experience both stronger positive selection, and lower selective constraint than other genes in the genome. Furthermore, the strength of selection may be modulated by expression level, with more abundant proteins experiencing weaker selective constraint, leading to the accumulation of more deleterious mutations. These findings show that snake venoms evolve by a combination of adaptive and neutral mechanisms, both of which explain their extraordinarily high rates of molecular evolution. In addition to positive selection, which optimizes efficacy of the venom in the short term, relaxed selective constraints for deleterious mutations can lead to more rapid turnover of individual proteins, and potentially to exploration of a larger venom phenotypic space.
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