Genes, modules and the evolution of cave fish

Cave fish provide a model system for exploring the genetic basis of regressive evolution. A proposal that regressive evolution (for example, eye loss) may result from pleiotropy, by selection on constructive traits (for example, improved taste) has received considerable recent interest as it contradicts the theory that regressive evolution results from neutral evolution. In this study, these theories are reviewed by placing the classical and molecular genetic studies of cave fish in a common framework. Sequence data and the wide range of intermediate sized eyes in hybrids between surface and cave fish suggest that currently there is no strong evidence supporting the notion that structural eye genes have been afflicted by destructive mutations. The hedgehog genes, which are suggested to reduce the primordial eye cup size in cavefish by expanded expression, are also not mutated. The as yet unidentified 'eye genes' revealed by crossing experiments seem primarily responsible for eye regression and determine eye development through hedgehog. Hybrids between different eye-reduced cave populations developing large 'back to surface eyes' support this. In such eyes, hh expression is restored by complementary restitution because of the recombination of 'eye genes', which were subjected to different destructive mutations in separately evolving cave fish populations. All regressive and constructive cave fish traits can be considered to result from genetic modules, each showing a comparable pattern of expression. The constructive and regressive modules are shown to inherit independently from each other, which does not support the view that eye regression is a spin off effect of the improvement of beneficial traits through pleiotropy. Heredity (2010) 105, 413-422; doi:10.1038/hdy.2009.184; published online 13 January 2010