Williams E J, Pal C, Hurst L D
Department of Biology and Biochemistry, University of Bath, Claverton Down, BA2 7AY, Bath, UK.
Gene. 2000 Aug 8;253(2):313-22. doi: 10.1016/s0378-1119(00)00233-x.
Signal peptides direct mature peptides to their appropriate cellular location, after which they are cleaved off. Very many random alternatives can serve the same function. Of all coding sequences, therefore, signal peptides might come closest to being neutrally evolving. Here we consider this issue by examining the molecular evolution of 76 mouse-rat orthologues, each with defined signal peptides. Although they do evolve rapidly, they evolve about half as fast as neutral sequences. This indicates that a substantial proportion of mutations must be under stabilizing selection. A few putative signal sequences lack a hydrophobic core and these tend to be more slowly evolving than others, indicating even stronger stabilizing selection. However, closer scrutiny suggests that some of these represent mis-annotations in GenBank. It is also likely that some of the substitutions are not neutral. We find, for example, that the rate of protein evolution correlates with that of the mature peptide. This may be a result of compensatory evolution. We also find that signal peptides of immune genes tend to be faster evolving than the average, which suggests an association with antagonistic co-evolution. Previous reports also indicated that the signal peptide of the imprinted gene, Igf2r, is also unusually fast evolving. This, it was hypothesized, might also be indicative of antagonistic co-evolution. Comparison of Igf2r's signal peptide evolution shows that, although it is not an outlier, its rate of evolution is comparable to that of many of the faster evolving immune system signal sequences and 5/6 of the amino acid changes do not conserve hydrophobicity. This is at least suggestive that there is something unusual about Igf2r's signal sequence.
信号肽将成熟肽引导至其合适的细胞位置，之后它们会被切除。许多随机的替代序列都能起到相同的作用。因此，在所有编码序列中，信号肽可能最接近中性进化。在这里，我们通过研究76对小鼠 - 大鼠直系同源物的分子进化来探讨这个问题，每对直系同源物都有明确的信号肽。尽管它们确实进化迅速，但进化速度约为中性序列的一半。这表明相当一部分突变必定受到稳定选择。一些推定的信号序列缺乏疏水核心，并且这些序列的进化往往比其他序列更慢，这表明存在更强的稳定选择。然而，更仔细的审查表明，其中一些在GenBank中代表错误注释。也有可能一些替代不是中性的。例如，我们发现蛋白质进化速率与成熟肽的进化速率相关。这可能是补偿进化的结果。我们还发现免疫基因的信号肽往往比平均水平进化得更快，这表明与拮抗协同进化有关。先前的报告也表明，印记基因Igf2r的信号肽进化也异常迅速。据推测，这也可能表明存在拮抗协同进化。对Igf2r信号肽进化的比较表明，尽管它不是异常值，但其进化速率与许多进化较快的免疫系统信号序列相当，并且六分之五的氨基酸变化并不保留疏水性。这至少表明Igf2r的信号序列存在一些不寻常之处。
