Weak negative and positive selection and the drift load at splice sites

Stepan V. Denisov, Georgii A. Bazykin, Roman Sutormin, Alexander V. Favorov, Andrey A. Mironov, Mikhail S. Gelfand, Alexey S. Kondrashov

Research output: Contribution to journalArticlepeer-review

Abstract

Splice sites (SSs) are short sequences that are crucial for proper mRNA splicing in eukaryotic cells, and therefore can be expected to be shaped by strong selection. Nevertheless, in mammals and in other intron-rich organisms, many of the SSs often involve nonconsensus (Nc), rather than consensus (Cn), nucleotides, and beyond the two critical nucleotides, the SSs are not perfectly conserved between species. Here, we compare the SS sequences between primates, and between Drosophila fruit flies, to reveal the pattern of selection acting at SSs. Cn-to-Nc substitutions are less frequent, and Nc-to-Cn substitutions are more frequent, than neutrally expected, indicating, respectively, negative and positive selection. This selection is relatively weak (1 < j4Nesj < 4), and has a similar efficiency in primates and in Drosophila. Within some nucleotide positions, the positive selection in favor of Nc-to-Cn substitutions is weaker than the negative selection maintaining already established Cn nucleotides; this difference is due to site-specific negative selection favoring current Nc nucleotides. In general, however, the strength of negative selection protecting the Cn alleles is similar in magnitude to the strength of positive selection favoring replacement of Nc alleles, as expected under the simple nearly neutral turnover. In summary, although a fraction of the Nc nucleotides within SSs is maintained by selection, the abundance of deleterious nucleotides in this class suggests a substantial genome-wide drift load.

Original languageEnglish (US)
Pages (from-to)1437-1447
Number of pages11
JournalGenome biology and evolution
Volume6
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • Drift load
  • Nearly neutral evolution
  • Negative selection
  • Positive selection
  • Splice sites
  • Splicing

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics

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