Protein dispensability and rate of evolution
Protein dispensability and rate of evolution
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DOI：
10.1038/35082561
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发表时间：
2001-06-28
期刊：
影响因子：
64.8
通讯作者：
Fraser, HB
中科院分区：
文献类型：
--
作者：
Hirsh, AE;Fraser, HB
如果蛋白质的进化在很大程度上是由于轻微有害的氨基酸替换(1，2)，那么对个体健康贡献较小的蛋白质的进化速度应该会更快。这一预测的基本原理是，相对不必要的蛋白质应该受到较弱的纯化选择，因此应该更快地积累温和有害的替代。虽然这一论点是在二十多年前提出的(3)，而且是进化论许多应用的基础(4)，但事实证明这一预测很难得到证实。事实上，最近的一项研究表明，小鼠基本基因的进化速度并不比非基本基因慢。因此，尽管广泛的序列分析已经支持了影响蛋白质进化速度的各种因素(6-12)，但蛋白质可分性和进化速度之间的关系仍然没有得到证实。在这里，我们使用酵母(13)中单基因缺失的高度平行生长分析的结果来评估蛋白质的可分配性，我们将其与基于对来自21个完全注释的基因组的序列进行比较的进化速度估计相关联。我们的分析揭示了蛋白质可分性和进化率之间的高度显著的关系，并解释了为什么通过必要和非必要蛋白质的分类比较无法检测到这种关系。这种关系是高度保守的，因此酵母中蛋白质的可有性也可以预测线虫的进化速度。
If protein evolution is due in large part to slightly deleterious amino acid substitutions(1,2), then the rate of evolution should be greater in proteins that contribute less to individual fitness. The rationale for this prediction is that relatively dispensable proteins should be subject to weaker purifying selection, and should therefore accumulate mildly deleterious substitutions more rapidly. Although this argument was presented(3) over twenty years ago, and is fundamental to many applications of evolutionary theory(4), the prediction has proved difficult to confirm. In fact, a recent study showed that essential mouse genes do not evolve more slowly than non-essential ones(5). Thus, although a variety of factors influencing the rate of protein evolution have been supported by extensive sequence analysis(6-12), the relationship between protein dispensability and evolutionary rate has remained unconfirmed. Here we use the results from a highly parallel growth assay of single gene deletions in yeast(13) to assess protein dispensability, which we relate to evolutionary rate estimates that are based on comparisons of sequences drawn from twenty-one fully annotated genomes. Our analysis reveals a highly significant relationship between protein dispensability and evolutionary rate, and explains why this relationship is not detectable by categorical comparison of essential versus nonessential proteins. The relationship is highly conserved, so that protein dispensability in yeast is also predictive of evolutionary rate in a nematode worm.