期刊
BIOINFORMATICS
卷 28, 期 2, 页码 176-183出版社
OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/btr635
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资金
- National Sciences and Engineering Research Council of Canada (NSERC) [RGPIN140221-10]
- Canada Research Chair (CRC)
Results: We design a phylogenetic hidden Markov model to identify protein regions relevant to type-I functional divergence. A C++ program, HMMDiverge, has been developed to estimate model parameters and to identify regions under type-I functional divergence. Simulations demonstrate that HMMDiverge can successfully identify protein regions under type-I functional divergence unless the discrepancy of substitution rates between subfamilies is very limited or the regions under functional divergence are very short. Applying HMMDiverge to G protein alpha subunits in animals, we identify a candidate region longer than 20 amino acids, which overlaps with the alpha-4 helix and the alpha 4-beta 6 loop in the GTPase domain with divergent rates of substitutions. These sites are different from those reported by an existing program, DIVERGE2. Interestingly, previous biochemical studies suggest the alpha-4 helix and the alpha 4-beta 6 loop are important to the specificity of the receptor-G protein interaction. Therefore, the candidate region reported by HMMDiverge highlights that the type-I functional divergence in G protein alpha subunits may be relevant to the change of receptor-G protein specificity after gene duplication. From these results, we conclude that HMMDiverge is a useful tool to identify regions under type-I functional divergence after gene duplication.
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