Meeting Abstract
Understanding the genetic basis of adaptation has broad implications not only for a basic understanding of evolution, but also for human pathologies given that many human diseases are a consequence of mis-adaptation to modern societies. The emerging model system Astyanax mexicanus has become an important fish species to address adaptation to extreme environments due to its unique ecology and the availability of genetic tools and genomic resources. Cave environments are typically dark and as a consequence nutrient deprived. We have previously shown that cavefish acquired impressive adaptations such as hyperphagia (increased appetite), starvation resistance and altered feeding behaviors to cope with these conditions. In this study we have found cavefish to display elevated blood sugar levels and strong insulin resistance compared to surface fish, but without any effect on the health of the fish. On the contrary, we show that these phenotypes are helping the cavefish to gain weight more quickly as part of their starvation resistance strategy. Using whole genome information of different cave and surface populations, we identified mutations in the insulin receptor of cavefish underlying the observed insulin resistant phenotypes. We use CRISPR mediated gene editing to show that this mutation is sufficient to cause a similar phenotype in zebrafish and provide evidence for strong selection of this allele in the wild. Interestingly, the same mutation is found in cases of Type 2 diabetic patients in human populations, raising the question whether cavefish can be used to gain insight into human glucose control homeostasis.
