The molecular evolution of signal peptides.
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.
Department of Biology and Biochemistry, University of Bath, Claverton Down, BA2 7AY, Bath, UK.
E J
EJ
Williams
C
C
Pal
L D
LD
Hurst
D019943:Amino Acid Substitution; D000818:Animals; D016208:Databases, Factual; D019143:Evolution, Molecular; D005787:Gene Frequency; D007109:Immunity / Q000235:genetics; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D021382:Protein Sorting Signals / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000235:genetics; D012641:Selection, Genetic
D021382:Protein Sorting Signals; D011506:Proteins; D017527:Receptor, IGF Type 2