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MBE Advance Access published online on October 6, 2009

Molecular Biology and Evolution, doi:10.1093/molbev/msp240
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© 2009 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Research Article

Inference and Characterization of Horizontally Transferred Gene Families using Stochastic Mapping

Ofir Cohen and Tal Pupko*

Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel

* To whom correspondence should be addressed: Tal Pupko, Tel: 972-3-6407693; Fax: 972-3-6422046, E-mail: talp{at}post.tau.ac.il

Received for publication July 22, 2009. Revision received September 21, 2009. Accepted for publication September 22, 2009.

Macro genomic events, in which genes are gained and lost, play a pivotal evolutionary role in microbial evolution. Nevertheless, probabilistic evolutionary models describing such events and methods for their robust inference are considerably less developed than existing methodologies for analyzing site-specific sequence evolution. Here we present a novel method for the inference of gains and losses of gene families. First, we develop probabilistic evolutionary models describing the dynamics of gene family content, which are more biologically realistic than previously suggested models. In our likelihood-based models, gains and losses are represented by transitions between presence and absence, given an underlying phylogeny. We employ a mixture-model approach in which we allow both the gain rate and the loss rate to vary among gene families. Second, we use these models together with the analytic implementation of stochastic mapping to infer branch specific events. Our novel methodology allows us to infer and quantify Horizontal Gene Transfer (HGT) events. This enables us to rank various gene families and lineages according to their propensity to undergo gains and losses. Applying our methodology to 4,873 gene families shows that (1) the novel mixture models describe the observed variability in gene family content among microbes significantly better than previous models; (2) The stochastic mapping approach enables accurate inference of gain and loss events based on simulations; (3) At least 34% of the gene families analyzed are inferred to have experienced HGT at least once during their evolution; (4) Gene families that were inferred to experience HGT are both enriched and depleted with respect to specific functional categories.

Key Words: phyletic pattern • probabilistic evolutionary models • mixture models • genome evolution • horizontal gene transfer • gene family content


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