{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T15:02:47Z","timestamp":1758121367112,"version":"3.38.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: A number of statistical phylogenetic methods have been proposed to identify type-I functional divergence in duplicate genes by detecting heterogeneous substitution rates in phylogenetic trees. A common disadvantage of the existing methods is that autocorrelation of substitution rates along sequences is not modeled. This reduces the power of existing methods to identify regions under functional divergence.<\/jats:p><jats:p>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 \u03b1 subunits in animals, we identify a candidate region longer than 20 amino acids, which overlaps with the \u03b1-4 helix and the \u03b14-\u03b26 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 \u03b1-4 helix and the \u03b14-\u03b26 loop are important to the specificity of the receptor\u2013G protein interaction. Therefore, the candidate region reported by HMMDiverge highlights that the type-I functional divergence in G protein \u03b1 subunits may be relevant to the change of receptor\u2013G 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.<\/jats:p><jats:p>Availability: C++ source codes of HMMDiverge and simulation programs used in this study, as well as example datasets, are available at http:\/\/info.mcmaster.ca\/yifei\/software\/HMMDiverge.html<\/jats:p><jats:p>Contact: \u00a0golding@mcmaster.ca<\/jats:p><jats:p>Supplementary Information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btr635","type":"journal-article","created":{"date-parts":[[2011,11,27]],"date-time":"2011-11-27T01:27:48Z","timestamp":1322357268000},"page":"176-183","source":"Crossref","is-referenced-by-count":11,"title":["Inferring sequence regions under functional divergence in duplicate genes"],"prefix":"10.1093","volume":"28","author":[{"given":"Yi-Fei","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biology, McMaster University, Hamilton, ON, Canada"}]},{"given":"G. 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