Significance of the study

The natural tendency for weight gain is damaging to human health. But under certain environmental conditions wherein nutrients are limited, this trait can be highly adaptive. Up to now, the basis in genetics of population level differences in appetite control and metabolism is still very much confusing. In this study, the researchers 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. They 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.

Results and Discussion

"The researchers provide evidence that the mutations in cavefish MC4R lead to reduced signaling efficiency and basal activity of MC4R, similar to an analogous mutation in human MC4R. In vivo data demonstrate that the cave allele of MC4R cosegregates with higher appetites. Interestingly, the hyperphagia cosegregating with the derived MC4R allele was age-dependent, because older fish did not show an increase in appetite (Figs. S2 and S3), although this finding could be explained, in part, by reduced growth rates of bigger fish due to tank size constraints. It is intriguing to note that certain human MC4R mutants have also been reported to affect childhood obesity specifically, with the impact being counteracted in older patients (22). Other genes might act to modulate appetite in older cavefish. It is also plausible that higher appetite is particularly important during early stages of fish development (<1-y-old) to obtain higher growth rates to the point where the fish can store sufficient reserves to make it through the starvation periods. It is worth mentioning that in some species of platyfish, MC4R copy number variation with both functional and nonfunctional alleles has been shown to play a role in energy balance and reproductive maturity (21). In any event, it is clear that MC4R is only one of a number of genes modulating feeding activity in the Tinaja and Molino cavefish, because the difference in level of appetite between Pachón individuals carrying the derived MC4R allele and those individuals homozygous for the WT allele is far less than the difference in level of appetite between the Tinaja or Molino fish and their surface conspecifics."

Source: http://www.pnas.org/content/112/31/9668.full

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