Within multi-exon genes, after introns are removed, the exons must be spliced back together. Splice-enhancer domains (exon sequences near the intronexon boundary) help to ensure that this happens correctly. As they fall within the proteins exon, they must also code for specific amino acids. This dual functionality must impact protein evolution.
In a new study published online this week in the open-access journal PLoS Biology, Joanna Parmley, Laurence Hurst, and colleagues probed the effect of this dual functionality on protein sequence evolution. By comparing mouse and human genes, they found evidence that these regions are subject to selective pressure. Therefore, the need to conserve splice enhancers means these sequence regions evolve at a lower-than-average rate. Further, they also saw that smaller exons in which more of the nucleotides are close to an intronexon boundary evolve more slowly.
In addition to this selection, the researchers found that the nucleotides in these regions are conserved and specific to splice enhancers. This is reflected in the resulting skew in amino acid content in the proteins in these areas. The authors conclude that the amino acid of a protein depends not only on its biological function, but also on its underlying gene structure and the presence of splice enhancers.
Protein evolution is known to be subject to other constraints: housekeeping genes with functions essential for cellular maintenance that are expressed in many tissues tend to evolve slowly, whereas nonessential genes frequently evolve more quickly. This study highlights that the proportion of a gene that falls in close proximity to an intron-exon boundary has a strong effect on the overall rate of protein evolution when compared with these other factors.
Parmley and colleagues also investigate retrotransposed genesgenes that have lost their introns. Such genes show accelerated evolution in the regions that were origin
Contact: Natalie Bouaravong
Public Library of Science