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Positive selection in alternatively spliced exons of human genes |
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| Authors: | Ramensky Vasily E Nurtdinov Ramil N Neverov Alexei D Mironov Andrei A Gelfand Mikhail S |
| Institution: | 1 Bioinformatics and Systems Biology Lab; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia 2 Department of Bioengineering and Bioinformatics, Moscow State University, Moscow, 119992, Russia 3 Bioinformatics Lab; State Scientific Center GosNIIGenetika, Moscow, 117545, Russia 4 Center of Molecular Diagnostics; Central Research Institute of Epidemiology, Moscow, 111123, Russia 5 Research and Training Center “Bioinformatics”, Institute for Information Transmission Problems (Kharkevich Institute), Russian Academy of Sciences, Moscow, 127994, Russia |
| Abstract: | 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. |
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