Positive selection in alternatively spliced exons of human genes.
Alternative splicing is a well-recognized mechanism of accelerated genome evolution. We have studied single-nucleotide polymorphisms and human-chimpanzee divergence in the exons of 6672 alternatively spliced human genes, with the aim of understanding the forces driving the evolution of alternatively spliced sequences. Here, we show that alternatively spliced exons and exon fragments (alternative exons) from minor isoforms experience lower selective pressure at the amino acid level, accompanied by selection against synonymous sequence variation. The results of the McDonald-Kreitman test suggest that alternatively spliced exons, unlike exons constitutively included in the mRNA, are also subject to positive selection, with up to 27% of amino acids fixed by positive selection.
Bioinformatics and Systems Biology Lab, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia. ramensky@imb.ac.ru
Vasily E
VE
Ramensky
Ramil N
RN
Nurtdinov
Alexei D
AD
Neverov
Andrei A
AA
Mironov
Mikhail S
MS
Gelfand
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D003062:Codon; D016208:Databases, Factual; D005091:Exons; D020224:Expressed Sequence Tags; D005796:Genes / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid
D003062:Codon