Footprints of natural selection at the mannose-6-phosphate isomerase locus in barnacles.

Abstract

The mannose-6-phosphate isomerase (<i>Mpi</i>) locus in <i>Semibalanus balanoides</i> has been studied as a candidate gene for balancing selection for more than two decades. Previous work has shown that <i>Mpi</i> allozyme genotypes (fast and slow) have different frequencies across Atlantic intertidal zones due to selection on postsettlement survival (i.e., allele zonation). We present the complete gene sequence of the <i>Mpi</i> locus and quantify nucleotide polymorphism in <i>S. balanoides</i>, as well as divergence to its sister taxon <i>Semibalanus cariosus</i> We show that the slow allozyme contains a derived charge-altering amino acid polymorphism, and both allozyme classes correspond to two haplogroups with multiple internal haplotypes. The locus shows several footprints of balancing selection around the fast/slow site: an enrichment of positive Tajima's D for nonsynonymous mutations, an excess of polymorphism, and a spike in the levels of silent polymorphism relative to silent divergence, as well as a site frequency spectrum enriched for midfrequency mutations. We observe other departures from neutrality across the locus in both coding and noncoding regions. These include a nonsynonymous trans-species polymorphism and a recent mutation under selection within the fast haplogroup. The latter suggests ongoing allelic replacement of functionally relevant amino acid variants. Moreover, predicted models of <i>Mpi</i> protein structure provide insight into the functional significance of the putatively selected amino acid polymorphisms. While footprints of selection are widespread across the range of <i>S. balanoides</i>, our data show that intertidal zonation patterns are variable across both spatial and temporal scales. These data provide further evidence for heterogeneous selection on <i>Mpi</i>.