A Mutation-Selection Model of Protein Evolution under Persistent Positive Selection.

A Mutation-Selection Model of Protein Evolution under Persistent Positive Selection.
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持续正选择下的蛋白质进化突变选择模型。

DOI:
10.1093/molbev/msab309
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发表时间:
2022-01-07
影响因子:
10.7
通讯作者:
Dos Reis M
Dos Reis M
中科院分区:
生物学1区
文献类型:
--
作者:
Tamuri AU;Dos Reis M

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我们使用群体遗传学的第一原理来模拟蛋白质在持续正选择(PPS)下的进化。PPS可能发生在生物体受到持续的环境变化,在适应性辐射,或在宿主-病原体相互作用。我们的突变选择模型表明PPS下的蛋白质进化是一个不可逆的马尔可夫过程,因此PPS下的蛋白质在氨基酸取代之间显示出强烈的不对称分布的选择系数。我们的模型表明,检测阳性选择的标准(其中ω是非同义密码子取代率与同义密码子取代率的比值)是保守的,实际上是任意的,因为在真实的蛋白质中,许多突变是高度有害的,即使在阳性选择位点也会被选择去除。我们使用PPS模型的惩罚似然实现成功地检测PPS植物RuBisCO和流感HA蛋白。通过直接估计蛋白质位点的选择系数,我们的推理过程绕过了使用ω作为选择的替代度量的需要,并提高了我们检测蛋白质中分子适应的能力。
We use first principles of population genetics to model the evolution of proteins under persistent positive selection (PPS). PPS may occur when organisms are subjected to persistent environmental change, during adaptive radiations, or in host–pathogen interactions. Our mutation–selection model indicates protein evolution under PPS is an irreversible Markov process, and thus proteins under PPS show a strongly asymmetrical distribution of selection coefficients among amino acid substitutions. Our model shows the criteria (where ω is the ratio of nonsynonymous over synonymous codon substitution rates) to detect positive selection is conservative and indeed arbitrary, because in real proteins many mutations are highly deleterious and are removed by selection even at positively selected sites. We use a penalized-likelihood implementation of the PPS model to successfully detect PPS in plant RuBisCO and influenza HA proteins. By directly estimating selection coefficients at protein sites, our inference procedure bypasses the need for using ω as a surrogate measure of selection and improves our ability to detect molecular adaptation in proteins.
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