Multiple evolutionary mechanisms contribute to the evolution of the MalS gene family in <i>S. cerevisiae</i>.

<p>(A) Overview of evolutionary mechanisms in the evolution of an ancestral gene with two conflicting activities (major function, red; minor function, blue). Duplication can help resolve this “adaptive conflict” by allowing optimization of these activities in two separate copies. Increased requirement for either of these activities, for example by changes in the environment, can first be met by duplication of the ancestral gene. Selection for increased gene dosage can help to preserve both copies until adaptive mutations optimize the different functions in separate copies. (B) Evolution of the promiscuous ancestral MalS enzyme into the seven present-day MalS alleles shows how different evolutionary forces contribute to the evolution of gene duplicates. Activity towards isomaltose-like sugars first existed only as a trace activity in the ancestral, preduplication enzyme. The nature of the binding pocket prevented simultaneous optimization of the major and minor function in the ancestral enzyme. Duplication allowed the (full) optimization of the two conflicting activities of the ancestral enzyme in separate copies. Several key residues in the enzymes' binding pocket responsible for these shifts in substrate specificity (shaded in grey) show signs of positive selection (indicated both in red and with red arrows; see also <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001446#pbio-1001446-g004" target="_blank">Figure 4</a>). Preservation of more recent, highly similar duplicates like Mal12–Mal32 may be mediated through gene dosage effects (see also <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001446#pbio.1001446.s013" target="_blank">Figure S9</a>). Sequences above each enzyme represent the nine variable residues in the binding pocket (numbering based on Ima1 sequence). AA changes that led to improvement of one of the hydrolyzing activities are shaded in grey.