Julenius Karin, Pedersen Anders Gorm
Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Mol Biol Evol. 2006 Nov;23(11):2039-48. doi: 10.1093/molbev/msl081. Epub 2006 Aug 4.
Some proteins are highly conserved across all species, whereas others diverge significantly even between closely related species. Attempts have been made to correlate the rate of protein evolution to amino acid composition, protein dispensability, and the number of protein-protein interactions, but in all cases, conflicting studies have shown that the theories are hard to confirm experimentally. The only correlation that is undisputed so far is that highly/broadly expressed proteins seem to evolve at a lower rate. Consequently, it has been suggested that correlations between evolution rate and factors like protein dispensability or the number of protein-protein interactions could be just secondary effects due to differences in expression. The purpose of this study was to analyze mammalian proteins/genes with known subcellular location for variations in evolution rates. We show that proteins that are exported (extracellular proteins) evolve faster than proteins that reside inside the cell (intracellular proteins). We find weak, but significant, correlations between evolution rates and expression levels, percentage of tissues in which the proteins are expressed (expression broadness), and the number of protein interaction partners. More important, we show that the observed difference in evolution rate between extra- and intracellular proteins is largely independent of expression levels, expression broadness, and the number of protein-protein interactions. We also find that the difference is not caused by an overrepresentation of immunological proteins or disulfide bridge-containing proteins among the extracellular data set. We conclude that the subcellular location of a mammalian protein has a larger effect on its evolution rate than any of the other factors studied in this paper, including expression levels/patterns. We observe a difference in evolution rates between extracellular and intracellular proteins for a yeast data set as well and again show that it is completely independent of expression levels.
一些蛋白质在所有物种中都高度保守，而另一些蛋白质即使在亲缘关系很近的物种之间也有显著差异。人们曾试图将蛋白质进化速率与氨基酸组成、蛋白质的必要性以及蛋白质 - 蛋白质相互作用的数量联系起来，但在所有情况下，相互矛盾的研究表明这些理论很难通过实验得到证实。到目前为止唯一无可争议的关联是，高表达/广泛表达的蛋白质似乎进化速率较低。因此，有人提出进化速率与蛋白质必要性或蛋白质 - 蛋白质相互作用数量等因素之间的关联可能只是由于表达差异导致的次要效应。本研究的目的是分析已知亚细胞定位的哺乳动物蛋白质/基因的进化速率变化。我们发现分泌型蛋白质（细胞外蛋白质）比驻留在细胞内的蛋白质（细胞内蛋白质）进化得更快。我们发现进化速率与表达水平、蛋白质表达的组织百分比（表达广度）以及蛋白质相互作用伙伴的数量之间存在微弱但显著的关联。更重要的是，我们表明细胞外和细胞内蛋白质之间观察到的进化速率差异在很大程度上独立于表达水平、表达广度和蛋白质 - 蛋白质相互作用的数量。我们还发现这种差异不是由细胞外数据集中免疫蛋白或含二硫键蛋白质的过度富集引起的。我们得出结论，哺乳动物蛋白质的亚细胞定位对其进化速率的影响比本文研究的任何其他因素都大，包括表达水平/模式。我们在酵母数据集中也观察到细胞外和细胞内蛋白质之间进化速率存在差异，并且再次表明这与表达水平完全无关。
