Maximum likelihood methods for detecting adaptive evolution after gene duplication

Abstract

The rapid accumulation of genomic sequences in public databases will finally allow large scale studies of gene family evolution, including evaluation of the role of positive Darwinian selection following a duplication event. This will be possible because recent statistical methods of comparing synonymous and nonsynonymous substitution rates permit reliable detection of positive selection at individual amino acid sites and along evolutionary lineages. Here, we summarize maximum-likelihood based methods, and present a framework for their application to analysis of gene families. Using these methods, we investigated the role of positive Darwinian selection in the ECP-EDN gene family of primates and the Troponin C gene family of vertebrates. We also comment on the limitations of these methods and discuss directions for further improvements.

A Maximum Likelihood Method for Detecting Functional Divergence at Individual Codon Sites, with Application to Gene Family Evolution

“…Both these gene families have been well studied. Evidence has been found for the action of positive Darwinian selection since the divergence of ECP and EDN (Zhang et al 1998;Bielawski and Yang 2003) but not since the divergence of the e and c globins (G. Aguileta, pers. commun.).…”

Relaxed Selection Among Duplicate Floral Regulatory Genes in Lamiales

“…1) were specified as foreground branches, thus allowing for different xÕs both over a subset of branches in the gene phylogeny and sites. This constraint has been used previously to test for positive selection following gene duplication (Bielawski and Yang 2003) and reflects a model of duplicate gene evolution whereby positive selection acts initially on duplicates followed by purifying selection in ancestral lineages (Hughes 1999). We used the modified branch-sites Model A of Zhang et al (2005) in order to avoid problems with an elevated type 1 error rate reported for older branch-sites models (Yang and Nielsen 2002), including a nested model with x 2 = 1 fixed (Model A null ).…”

“…3, Table 2), consistent with strong purifying selection acting on duplicate copies. Second, a signature of positive selection is absent from branchsites models, which have increased power to detect adaptive evolution acting during discrete intervals of a geneÔs evolutionary history (Bielawski and Yang 2003). For the modified branch-sites Model A (Table 2), we specified the two branches immediately following the duplication of FLO or DEF (x 1 ) as foreground branches, and those prior to the duplication (x 0 ) as well as daughter branches (x 2 , x 3 ) as background branches (Fig.…”

“…2). This reflects a model whereby duplicated genes may initially experience positive selection, followed by the return of purifying selection along later branches in the gene phylogeny (Bielawski and Yang 2003) which could result from (i) gene duplicates acquiring new functions distinct from the ancestral single-copy gene (neofunctionalization sensu Force et al [1999]) or (ii) adaptive evolution acting on subfunctionalized protein coding domains constrained to suboptimal performance in Table 2. Parameter estimates (xÕs and proportions for site classes) and likelihood scores for sites models (M0-M8) and branch-sites models Background x 0.070 1.000 0.070 1.000 Foreground x 0.070 1.000 1.000 1.000…”

“…Interestingly, in this case functional evidence from representative Rosid (A. thaliana; AG and SHP1/2) and Asterid (A. majus; PLE and FAR) model taxa shows that the regulatory role of individual paralogs has resolved differently within independently evolving lineages, lending further support to a subfunctionalization hypothesis for preservation of ancient MADS box paralogs. However, signatures of adaptive evolution are increasingly reported among coding regions of genes following duplication as statistical models improve (e.g., Bielawski and Yang 2003) and have been detected previously within noncoding regulatory sequences of several other MADS box genes derived from the most recent polyploidization event in A. thaliana (Moore and Purugganan 2005). In addition, subfunctionalization and adaptive evolution are not mutually exclusive hypotheses.…”