Genetic variation in HIF signaling underlies quantitative variation in physiological and life history traits within lowland butterfly populations

Oxygen conductance to the tissues determines aerobic metabolic performance in most eukaryotes but has cost/benefit tradeoffs. Here we examine in lowland populations of a butterfly a genetic polymorphism affecting oxygen conductance via the hypoxia inducible factor (HIF) pathway, which senses intracellular oxygen and controls the development of oxygen delivery networks. Genetically distinct clades of Glanville fritillary (Melitaea cinxia) across a continental scale maintain, at intermediate frequencies, alleles in a metabolic enzyme (succinate dehydrogenase, SDH) that regulates hypoxia inducible factor (HIF-1α). One Sdhd allele was associated with reduced SDH activity rate, two-fold greater cross-sectional area of tracheoles in flight muscle, and better flight performance. Butterflies with less tracheal development had greater post-flight hypoxia signaling, swollen, disrupted mitochondria and accelerated aging of flight metabolic performance. Allelic associations with metabolic and aging...