Abstract

Significance The propensity for weight gain is detrimental to modern human health. However, under environmental conditions where nutrients are limiting, this trait can be highly adaptive. Currently, the genetic basis of population level differences in appetite control and metabolism is still largely mysterious. Here, we describe changes in metabolism that evolved in the small tetra Astyanax mexicanus as it adapted from surface rivers to the nutrient-poor environment found in caves. We identified coding mutations in melanocortin 4 receptor responsible for an increase in appetite and starvation resistance of cavefish compared with surface fish populations. These results provide important genetic insights into metabolic evolution and show that mutations in a single gene can have profound effects on multiple physiological adaptations.