PT - JOURNAL ARTICLE AU - John E. Pool AU - Dylan T. Braun AU - Justin B. Lack TI - Parallel Evolution of Cold Tolerance Within <em>Drosophila melanogaster</em> AID - 10.1101/063545 DP - 2016 Jan 01 TA - bioRxiv PG - 063545 4099 - http://biorxiv.org/content/early/2016/07/12/063545.short 4100 - http://biorxiv.org/content/early/2016/07/12/063545.full AB - Drosophila melanogaster originated in tropical Africa before expanding into strikingly different temperate climates in Eurasia and beyond. Here, we show that elevated cold tolerance has arisen at least three times within this species: beyond the well-studied non-African case, we show that populations from the highlands of Ethiopia and South Africa have significantly increased cold tolerance as well. We observe greater cold tolerance in outbred versus inbred flies, but only in populations with higher inversion frequencies. Each cold-adapted population shows lower inversion frequencies than a closely-related warm-adapted population, suggesting that inversion frequencies may decrease with altitude in addition to latitude. Using the FST-based “Population Branch Excess” statistic (PBE), we found only limited evidence for parallel genetic differentiation at the scale of ~4 kb windows, specifically between Ethiopian and South African cold-adapted populations. And yet, when we looked for single nucleotide polymorphisms (SNPs) with codirectional frequency change in two or three cold-adapted populations, strong genomic enrichments were observed from all comparisons. These findings could reflect an important role for selection on standing genetic variation leading to “soft sweeps”. One SNP showed sufficient codirectional frequency change in all cold-adapted populations to achieve experiment-wide significance: an intronic variant in the synaptic gene Prosap. More generally, proteins involved in neurotransmission were enriched as potential targets of parallel adaptation. The ability to study cold tolerance evolution in a parallel framework will enhance this classic study system for climate adaptation.