Subterranean Fishes of the World

4271

2019

AIM 2019

21

Similar environments often result in the repeated evolution of the same traits in multiple, independently evolved populations. To understand how and why these traits evolve, it is necessary to identify and functionally validate causal mutations. In recent years, many loci responsible for natural variation have been identified by genetic mapping. A few studies have identified the genetic changes likely to be responsible for this phenotypic variation. However, the functional consequences of these changes in the organism itself or in an ecologically-relevant, closely-related species remain unclear. Few studies have achieved this level of resolution. This challenge must be overcome to understand how and why certain evolutionary outcomes occur repeatedly. We have pioneered genome-editing approaches in A. mexicanus to elucidate the genetic basis of complex trait evolution, and to evaluate how traits evolve repeatedly. Albinism is one of the hallmarks of cave species, and this trait has evolved repeatedly in independently derived cave lineages. Using the CRISPR/Cas9 genome editing system, we mutated the oculocutaneous albinism II (oca2) gene, a candidate gene for causing albinism in multiple, independently evolved cavefish populations. Using these methods, we have demonstrated that oca2 is the causative gene responsible for albinism in two cavefish populations. Further, generation of these fish has allowed us to examine the role of oca2 in other cavefish traits, including catecholamine levels and behavior. Moving forward, these approaches can be used to understand the genetic basis of complex traits, how specific genetic changes lead to alterations in developmental programs, and ultimately, how genetic variants in cavefish contribute to fitness.

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