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Genome Biol Evol. 2014 May 14;6(6):1437-47. doi: 10.1093/gbe/evu100.

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

Author information

1
A.A. Kharkevich Insitute for Information Transmission Problems RAS, Moscow, Russia.
2
A.A. Kharkevich Insitute for Information Transmission Problems RAS, Moscow, RussiaFaculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia.
3
Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia.
4
Division of Oncology Biostatistics, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MDLaboratory of System Biology and Computational Genetics, Department of Computational System Biology, N.I. Vavilov Institute of General Genetics, Moscow, RussiaLaboratory of Bioinformatics, State Research Institute of Genetics and Selection of Industrial Microorganism (GosNIIGenetika), Moscow, Russia.
5
A.A. Kharkevich Insitute for Information Transmission Problems RAS, Moscow, RussiaFaculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, Russia gelfand@iitp.ru.
6
Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Moscow, RussiaLife Sciences Institute and Department of Ecology and Evolutionary Biology, University of Michigan.

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 < |4Nes| < 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.

KEYWORDS:

drift load; nearly neutral evolution; negative selection; positive selection; splice sites; splicing

PMID:
24966225
PMCID:
PMC4079205
DOI:
10.1093/gbe/evu100
[Indexed for MEDLINE]
Free PMC Article

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