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Orthology confers intron position conservation

Henricson, Anna (författare)
Stockholms universitet,Institutionen för biokemi och biofysik
Forslund, Kristoffer (författare)
Stockholms universitet,Institutionen för biokemi och biofysik
Sonnhammer, Erik L. L. (författare)
Stockholms universitet,Institutionen för biokemi och biofysik
 (creator_code:org_t)
2010-07-02
2010
Engelska.
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 11:412
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Background: With the wealth of genomic data available it has become increasingly important to assign putative protein function through functional transfer between orthologs. Therefore, correct elucidation of the evolutionary relationships among genes is a critical task, and attempts should be made to further improve the phylogenetic inference by adding relevant discriminating features. It has been shown that introns can maintain their position over long evolutionary timescales. For this reason, it could be possible to use conservation of intron positions as a discriminating factor when assigning orthology. Therefore, we wanted to investigate whether orthologs have a higher degree of intron position conservation (IPC) compared to non-orthologous sequences that are equally similar in sequence. Results: To this end, we developed a new score for IPC and applied it to ortholog groups between human and six other species. For comparison, we also gathered the closest non-orthologs, meaning sequences close in sequence space, yet falling just outside the ortholog cluster. We found that ortholog-ortholog gene pairs on average have a significantly higher degree of IPC compared to ortholog-closest non-ortholog pairs. Also pairs of inparalogs were found to have a higher IPC score than inparalog-closest non-inparalog pairs. We verified that these differences can not simply be attributed to the generally higher sequence identity of the ortholog-ortholog and the inparalog-inparalog pairs. Furthermore, we analyzed the agreement between IPC score and the ortholog score assigned by the InParanoid algorithm, and found that it was consistently high for all species comparisons. In a minority of cases, the IPC and InParanoid score ranked inparalogs differently. These represent cases where sequence and intron position divergence are discordant. We further analyzed the discordant clusters to identify any possible preference for protein functions by looking for enriched GO terms and Pfam protein domains. They were enriched for functions important for multicellularity, which implies a connection between shifts in intronic structure and the origin of multicellularity. Conclusions: We conclude that orthologous genes tend to have more conserved intron positions compared to non-orthologous genes. As a consequence, our IPC score is useful as an additional discriminating factor when assigning orthology.

Ämnesord

NATURVETENSKAP  -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)

Nyckelord

biokemi, inriktning teoretisk kemi
Biochemistry with Emphasis on Theoretical Chemistry

Publikations- och innehållstyp

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