Subterranean Fishes of the World

3905

2016

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 cavefish species to address adaptation to extreme environments due to its unique ecology and the availability of genetic tools and genomic resources. We have previously shown that cavefish acquired impressive metabolic adaptations such as hyperphagia (increased appetite), starvation resistance and altered feeding behaviors to cope with the typically nutrient deprived cave environments. Here, we have focused on the insulin transduction pathway and its role on glucose and fat homeostasis in cave and surface forms of A. mexicanus. Interestingly, we detected very low insulin levels in cavefish (compared to surface fish) partially due to lower numbers of beta-insulin producing cells in the pancreas. In addition, we observed strong insulin resistance in cavefish when administered with ectopic insulin. Despite the consequential elevated and highly fluctuating blood glucose levels, cavefish live long and healthy lives, probing the question whether they have acquired mechanisms allowing them to cope with extreme nutritional levels. Taking advantage of the newly available genome of Astyanax mexicanus, we identified mutations in the insulin receptor of cavefish. Importantly, the same mutations were found in cases of insulin resistant patients in human populations. Our findings in independently derived cavefish populations suggest that cavefish are inherently insulin resistant, potentially as an additional strategy to acquire better starvation resistance. We are currently using genome editing to functionally test these and other candidate mutations in zebrafish and cavefish itself to study in detail the molecular mechanisms underlying the metabolic adaptation of cavefish to the extreme and nutrient poor environments.

1

23rd International Conference on Subterranean Biology

2016

2016

2016