Epistatically interacting substitutions are enriched during adaptive protein evolution.
Epistatically interacting substitutions are enriched during adaptive protein evolution.
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DOI：
10.1371/journal.pgen.1004328
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发表时间：
2014-05
期刊：
影响因子：
4.5
通讯作者：
Bloom JD
中科院分区：
文献类型：
--
作者：
Gong LI;Bloom JD
Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play. Mutations can fix during evolution for two reasons: they can be beneficial and fix for adaptive reasons, or they can be neutral or deleterious and fix solely by chance. Most studies focus on adaptation, where the evolving population is increasing in fitness due to a new selection pressure. Such studies have found an important evolutionary role for epistasis, the phenomenon where the effect of one mutation depends on another mutation. But adaptation only accounts for a fraction of overall evolutionary change. Here we investigate whether epistasis is as common during non-adaptive as adaptive evolution. We do this by comparing the same protein from human and swine influenza. Human influenza is constantly adapting to escape from the immunity that people acquire from previous influenza infections. But swine influenza is under less pressure to escape from acquired immunity since pigs have shorter lifetimes and are less likely to be infected with influenza multiple times. We find that epistasis is less common during the evolution of the swine influenza protein than its human influenza counterpart. Overall, our results suggest that mutations that interact via epistasis are more likely to fix during adaptive evolution.
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DOI：
10.1098/rstb.2000.0716
发表时间：
2000-11-29
影响因子：
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作者：
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通讯作者：
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