Recent Strong Positive Selection on Drosophila melanogaster HDAC6, a Gene Encoding a Stress Surveillance Factor, as Revealed by Population Genomic Analysis

Abstract

Based on nearly complete genome sequences from a variety of organisms, data on naturally occurring genetic variation on the scale of hundreds of loci to entire genomes have been collected in recent years. In parallel, new statistical approaches (such as the composite likelihood ratio and "SweepFinder" tests) have been developed to infer evidence of recent positive selection from these data and to localize the target of selection. Here, we apply these methods to the X chromosome of Drosophila melanogaster in an effort to map genes involved in ecological adaptation. Using slight modifications of these tests that increase their robustness against past demographic changes, we detected evidence that recent strongly positive selection has been acting on a 2.7-kb region in an ancestral African population. This region overlaps with the 3' end of HDAC6, a gene that encodes a newly characterized stress surveillance factor. HDAC6 is an unusual histone deacetylase being localized in the cytoplasm. Its ubiquitin-binding and tubulin-deacetylase activities suggest that HDAC6 is very different from other histone deacetylases. Indeed, recent discoveries have shown that HDAC6 is a key regulator of cytotoxic stress resistance.