Correlated evolution of nucleotide positions within splice sites in mammals

Stepan Denisov, Georgii Bazykin, Alexander Favorov, Andrey Mironov, Mikhail Gelfand

Research output: Contribution to journalArticle

Abstract

Splice sites (SSs)-short nucleotide sequences flanking introns-are under selection for spliceosome binding, and adhere to consensus sequences. However, non-consensus nucleotides, many of which probably reduce SS performance, are frequent. Little is known about the mechanisms maintaining such apparently suboptimal SSs. Here, we study the correlations between strengths of nucleotides occupying different positions of the same SS. Such correlations may arise due to epistatic interactions between positions (i.e., a situation when the fitness effect of a nucleotide in one position depends on the nucleotide in another position), their evolutionary history, or to other reasons. Within both the intronic and the exonic parts of donor SSs, nucleotides that increase (decrease) SS strength tend to cooccur with other nucleotides increasing (respectively, decreasing) it, consistent with positive epistasis. Between the intronic and exonic parts of donor SSs, the correlations of nucleotide strengths tend to be negative, consistent with negative epistasis. In the course of evolution, substitutions at a donor SS tend to decrease the strength of its exonic part, and either increase or do not change the strength of its intronic part. In acceptor SSs, the situation is more complicated; the correlations between adjacent positions appear to be driven mainly by avoidance of the AG dinucleotide which may cause aberrant splicing. In summary, both the content and the evolution of SSs is shaped by a complex network of interdependences between adjacent nucleotides that respond to a range of sometimes conflicting selective constraints.

Original languageEnglish (US)
Article numbere0144388
JournalPLoS One
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Mammals
Nucleotides
nucleotides
mammals
RNA Splice Sites
epistasis
spliceosomes
Spliceosomes
consensus sequence
Consensus Sequence
Complex networks
Introns
introns
History
Substitution reactions
nucleotide sequences
history

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Correlated evolution of nucleotide positions within splice sites in mammals. / Denisov, Stepan; Bazykin, Georgii; Favorov, Alexander; Mironov, Andrey; Gelfand, Mikhail.

In: PLoS One, Vol. 10, No. 12, e0144388, 01.12.2015.

Research output: Contribution to journalArticle

Denisov, Stepan ; Bazykin, Georgii ; Favorov, Alexander ; Mironov, Andrey ; Gelfand, Mikhail. / Correlated evolution of nucleotide positions within splice sites in mammals. In: PLoS One. 2015 ; Vol. 10, No. 12.
@article{864dc204843d4e8ca65e7d1ac281a3e5,
title = "Correlated evolution of nucleotide positions within splice sites in mammals",
abstract = "Splice sites (SSs)-short nucleotide sequences flanking introns-are under selection for spliceosome binding, and adhere to consensus sequences. However, non-consensus nucleotides, many of which probably reduce SS performance, are frequent. Little is known about the mechanisms maintaining such apparently suboptimal SSs. Here, we study the correlations between strengths of nucleotides occupying different positions of the same SS. Such correlations may arise due to epistatic interactions between positions (i.e., a situation when the fitness effect of a nucleotide in one position depends on the nucleotide in another position), their evolutionary history, or to other reasons. Within both the intronic and the exonic parts of donor SSs, nucleotides that increase (decrease) SS strength tend to cooccur with other nucleotides increasing (respectively, decreasing) it, consistent with positive epistasis. Between the intronic and exonic parts of donor SSs, the correlations of nucleotide strengths tend to be negative, consistent with negative epistasis. In the course of evolution, substitutions at a donor SS tend to decrease the strength of its exonic part, and either increase or do not change the strength of its intronic part. In acceptor SSs, the situation is more complicated; the correlations between adjacent positions appear to be driven mainly by avoidance of the AG dinucleotide which may cause aberrant splicing. In summary, both the content and the evolution of SSs is shaped by a complex network of interdependences between adjacent nucleotides that respond to a range of sometimes conflicting selective constraints.",
author = "Stepan Denisov and Georgii Bazykin and Alexander Favorov and Andrey Mironov and Mikhail Gelfand",
year = "2015",
month = "12",
day = "1",
doi = "10.1371/journal.pone.0144388",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Correlated evolution of nucleotide positions within splice sites in mammals

AU - Denisov, Stepan

AU - Bazykin, Georgii

AU - Favorov, Alexander

AU - Mironov, Andrey

AU - Gelfand, Mikhail

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Splice sites (SSs)-short nucleotide sequences flanking introns-are under selection for spliceosome binding, and adhere to consensus sequences. However, non-consensus nucleotides, many of which probably reduce SS performance, are frequent. Little is known about the mechanisms maintaining such apparently suboptimal SSs. Here, we study the correlations between strengths of nucleotides occupying different positions of the same SS. Such correlations may arise due to epistatic interactions between positions (i.e., a situation when the fitness effect of a nucleotide in one position depends on the nucleotide in another position), their evolutionary history, or to other reasons. Within both the intronic and the exonic parts of donor SSs, nucleotides that increase (decrease) SS strength tend to cooccur with other nucleotides increasing (respectively, decreasing) it, consistent with positive epistasis. Between the intronic and exonic parts of donor SSs, the correlations of nucleotide strengths tend to be negative, consistent with negative epistasis. In the course of evolution, substitutions at a donor SS tend to decrease the strength of its exonic part, and either increase or do not change the strength of its intronic part. In acceptor SSs, the situation is more complicated; the correlations between adjacent positions appear to be driven mainly by avoidance of the AG dinucleotide which may cause aberrant splicing. In summary, both the content and the evolution of SSs is shaped by a complex network of interdependences between adjacent nucleotides that respond to a range of sometimes conflicting selective constraints.

AB - Splice sites (SSs)-short nucleotide sequences flanking introns-are under selection for spliceosome binding, and adhere to consensus sequences. However, non-consensus nucleotides, many of which probably reduce SS performance, are frequent. Little is known about the mechanisms maintaining such apparently suboptimal SSs. Here, we study the correlations between strengths of nucleotides occupying different positions of the same SS. Such correlations may arise due to epistatic interactions between positions (i.e., a situation when the fitness effect of a nucleotide in one position depends on the nucleotide in another position), their evolutionary history, or to other reasons. Within both the intronic and the exonic parts of donor SSs, nucleotides that increase (decrease) SS strength tend to cooccur with other nucleotides increasing (respectively, decreasing) it, consistent with positive epistasis. Between the intronic and exonic parts of donor SSs, the correlations of nucleotide strengths tend to be negative, consistent with negative epistasis. In the course of evolution, substitutions at a donor SS tend to decrease the strength of its exonic part, and either increase or do not change the strength of its intronic part. In acceptor SSs, the situation is more complicated; the correlations between adjacent positions appear to be driven mainly by avoidance of the AG dinucleotide which may cause aberrant splicing. In summary, both the content and the evolution of SSs is shaped by a complex network of interdependences between adjacent nucleotides that respond to a range of sometimes conflicting selective constraints.

UR - http://www.scopus.com/inward/record.url?scp=84955458723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955458723&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0144388

DO - 10.1371/journal.pone.0144388

M3 - Article

C2 - 26642327

AN - SCOPUS:84955458723

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e0144388

ER -