Rock, paper, scissors: harnessing complementarity in ortholog detection methods improves comparative genomic inference.
Bottom Line: OD methods comprise a wide variety of approaches, each with their own benefits and costs under a variety of evolutionary and practical scenarios.In head-to-head comparisons, we find that these algorithms significantly outperform one another for 38-45% of the genes analyzed.Further, this improvement in alignment quality yields more confidently aligned sites and higher levels of overall conservation, while simultaneously detecting of up to 180% more positively selected sites.
Affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, University of California, San Francisco, San Francisco, California.Show MeSH
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Mentions: We next sought to examine the biological significance of some of the positively selected sites identified uniquely by MOSAIC. This led us to Tryptase Alpha/Beta 1 (TPSAB1), a tetrameric serine protease that has been implicated in the pathogenesis of asthma (Taira et al. 2002; Cui et al. 2014), heart disease (Bot et al. 2014), inflammatory bowel disease (Hamilton et al. 2011), and other disorders with allergic and/or inflammatory components (Sommerhoff and Schaschke 2007). Shown in Figure 7 is the three-dimensional structure of a TPSAB1 tetramer with inhibitor (white) bound (Costanzo et al. 2008). In orange, distal to the active site, is the positively selected residue detected by component methods and by MOSAIC. Note that positive selection at this location is active only outside of the great apes, with a fixed lysine observed in human, chimp, gorilla, and orangutan (Figure S9 and Figure S10).
Affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, University of California, San Francisco, San Francisco, California.