Clines and adaptive evolution in the methuselah gene region in Drosophila melanogaster

In an effort to characterize further the patterns of selection and adaptive evolution at the methuselah locus in Drosophila species, we extended an analysis of geographical variation to include single nucleotide polymorphisms (SNPs) in adjacent genes on either side of the mth locus, and examined the molecular variation in a neighbouring methuselah paralogue (mth2). An analysis of 13 SNPs spanning a region of nearly 19 kilobases surrounding the mth locus demonstrated that a clinal pattern associated with the most common mth haplotype does not extend to adjacent gene loci, providing compelling evidence that the clinal pattern results from selection on as yet unidentified sites associated with the functional mth locus. mth2 exhibited a significant pattern of adaptive divergence among D. melanogaster, D. simulans and D. yakuba similar to that seen at mth. However, Ka : Ks ratios indicate a difference in levels of functional constraint at the two methuselah, loci with mth2 exhibiting a five- to six-fold reduction in levels of amino acid divergence relative to mth.