Melanocortin 4 receptor mutations contribute to the adaptation of cavefish to nutrient-poor conditions
- Permanent Link:
- Melanocortin 4 receptor mutations contribute to the adaptation of cavefish to nutrient-poor conditions
- Series Title:
- Proc. Natl. Acad. Sci
- Aspiras, Ariel C.
Borowsky, Richard L.
Tabin, Clifford J.
- National Academy of Sciences
- Publication Date:
- Subjects / Keywords:
- Astyanax Mexicanus ( local )
Cavefish ( local )
Mc4r ( local )
Metabolic Evolution ( local )
Hyperphagia ( local )
- serial ( sobekcm )
- Despite recent advances in the understanding of morphological evolution, the genetic underpinnings of behavioral and physiological evolution remain largely unknown. Here, we study the metabolic changes that evolved in independently derived populations of the Mexican cavefish, Astyanax mexicanus. A hallmark of cave environments is scarcity of food. Cavefish populations rely almost entirely on sporadic food input from outside of the caves. To survive under these conditions, cavefish have evolved a range of adaptations, including starvation resistance and binge eating when food becomes available. The use of these adaptive strategies differs among independently derived cave populations. Although all cavefish populations tested lose weight more slowly than their surface conspecifics during restricted rations, only a subset of cavefish populations consume more food than their surface counterparts. A candidate gene-based screen led to the identification of coding mutations in conserved residues of the melanocortin 4 receptor (MC4R) gene, contributing to the insatiable appetite found in some populations of cavefish. Intriguingly, one of the mutated residues has been shown to be linksed to obesity in humans. We demonstrate that the allele results in both reduced maximal response and reduced basal activity of the receptor in vitro. We further validate in vivo that the mutated allele contributes to elevated appetite, growth, and starvation resistance. The allele appears to be fixed in cave populations in which the overeating phenotype is present. The presence of the same allele in multiple caves appears to be due to selection from standing genetic variation present in surface populations.
- Original Version:
- Proc. Natl. Acad. Sci, Vol. 112, no. 31 (2015-08-04).
- Source Institution:
- University of South Florida Library
- Holding Location:
- University of South Florida
- Rights Management:
- This object is protected by copyright, and is made available here for research and educational purposes. Permission to reuse, publish, or reproduce the object beyond the bounds of Fair Use or other exemptions to copyright law must be obtained from the copyright holder.
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