Estimating the Influence of Selection on the Variable Amino Acid Sites of the Cytochrome b Protein Functional Domains

Abstract

We evaluated the effects of selection on the molecular evolution of the functional domains of the mammalian cytochrome b gene as it relates to physicochemical properties shown to correlate with rates of amino acid replacement. Two groups of mammals were considered: pocket gophers of the rodent family Geomyidae, and cetaceans and ungulates of the monophyletic taxon Cetartopdactyla. Several characteristics of cytochrome b evolution were common to both mammal groups. The evolution of the matrix domain reflected the region's relative lack of function. Goodness of fit to neutral expectations indicated that external influences have had very little effect on the evolution of the matrix, although in some cases conservative and moderate changes have been favored. Although rates of synonymous nucleotide substitution have been relatively high, the transmembrane domain exhibited poor goodness of fit to neutral expectations. However, the evolution of the transmembrane domain has been constrained by negative selection, allowing a preponderance of conservative and moderate amino acid replacements. We hypothesize that a high rate of substitution is maintained in spite of negative selection because the codons of the transmembrane coding region are predisposed to conservative changes in all amino acid properties. The evolutionary patterns of the intermembrane domain in pocket gophers and cetartiodactyls, however, were very different. Changes inferred from the pocket gopher phylogenetic tree exhibited a significant fit to neutral expectations for each of the amino acid properties. Changes inferred from the cetartiodactyl tree exhibited significant fit to neutral expectations for polarity and isoelectric point, but not for composition, molecular volume, polar requirement, or hydropathy. In each case, lack of fit was due to selection that promoted conservative or moderate change, with the noteworthy exception of polar requirement. We detected an unexpectedly large change in polar requirement (from aspartic acid to threonine) in two separate lineages (Camelus bactrianus and all cetaceans) at amino acid position 159. This inferred change occurred in a region of the cyt-b protein that directly interacts with external surface proteins of the cytochrome bc(1) complex and resulted in a reversion to a more common character state in vertebrates.

Population genetics of microbial pathogens estimated from multilocus sequence typing (MLST) data

“…TreeSAAP, in contrast, still showed evidence of significant (P < 0.01) destabilizing selection (n TS ) in almost all of the same gene regions, although at a lower level (Table 2). This difference again reaffirms the higher sensitivity of the evolutionary model of McClellan and McCracken (2001) for detecting adaptive selection. As reported before by Anisimova et al (2001Anisimova et al ( ,2002, both power and accuracy of the LRT and Bayes tests decrease as sample size diminishes, especially when the sequences are highly similar.…”

“…Hence, in addition to estimating adaptive selection under codonsubstitution models M2, M3, and M8, we also estimated adaptive selection in terms of 31 quantitative biochemical properties using the model of McClellan and McCracken (2001) as implemented in TreeSAAP 3.2 (Woolley et al, 2003). No study has shown how tree topology and recombination affect the performance of the amino acid-property-based models implemented in Tree-SAAP.…”

“…Consequently, evolutionary models that do not allow for selection heterogeneity among sites, such as the one implemented by Nei and Gojobori (1986), will certainly not detect those few sites under positive selection. Several evolutionary models exist that account for site-specific differences on adaptive selection at the protein level (Nielsen and Yang, 1998;Yang et al, 2000a;McClellan and McCracken, 2001;Yang and Swanson, 2002), and their utility has been already demonstrated (e.g., Yang et al, 2000a,b;Haydon et al, 2001;Yang and Nielsen, 2002;McClellan et al, 2005); however, MLST data are not usually examined using these approaches.…”

Assessing and improving the accuracy of detecting protein adaptation with the TreeSAAP analytical software

“…A new family of methods recently has been proposed that approaches the question of amino acid replacement diagnosis using changes in physicochemical amino acid properties [6], [21], [11]. The use of amino acid properties results in a high degree of resolution that is more sensitive than the dN/dS approach [12], [16], and allows for the detailed diagnosis of individual amino acid changes in the context of the structure and function of proteins [1].…”

“…Substitution events are then inferred on each phylogenetic branch by directly comparing the hypothetical ancestral sequence at the basal end with the sequence at the terminal end. The ratio of inferred amino acid replacements to evolutionary pathways [11] is then calculated and used as a null hypothesis for the rate of random change for the sequence alignment. The overall pattern of inferred substitution is then compared to the distribution estimated using the null hypothesis to produce a series of z-scores to determine if certain magnitudes of change deviate from neutral expectations.…”