Skip to main content
eScholarship
Open Access Publications from the University of California

Negative selection pressure against premature protein truncation is reduced by alternative splicing and diploidy

  • Author(s): Lee, Christopher
  • et al.
Abstract

The importance of alternative splicing in many genomes has raised interesting questions about its role in evolution. We analyzed 13 384 full-length transcript isoforms from human and 2227 isoforms from mouse to identify sequences containing premature termination codons (PTCs) that are likely targets of mRNA nonsensemediated decay. We found that alternatively spliced isoforms have a much higher frequency of PTCs (11.1%) compared with the major transcript form of each gene (3.7%). On the X chromosome, which is generally expressed as a single copy, the overall PTC rate was much lower (3.5%, versus 8.9% on diploid autosomes), and the effect of alternative splicing was enhanced. Thus, diploidy and alternative splicing each increased tolerance for PTC by about threefold, as approximately additive effects. These data suggest that nonsense mediated decay might itself reduce negative selection pressure during evolution, via rapid degradation of aberrant transcripts that might yield dominant negative phenotypes.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Main Content
Current View