Genetic mapping of metabolic traits in the blind Mexican cavefish reveals sex-dependent quantitative trait loci associated with cave adaptation

Misty R. Riddle, Ariel Aspiras, Fleur Damen, Suzanne McGaugh, Julius A. Tabin, Clifford J. Tabin

Research output: Contribution to journalArticlepeer-review


Background: Despite a longstanding interest in understanding how animals adapt to environments with limited nutrients, we have incomplete knowledge of the genetic basis of metabolic evolution. The Mexican tetra, Astyanax mexicanus, is a species of fish that consists of two morphotypes; eyeless cavefish that have adapted to a low-nutrient cave environment, and ancestral river-dwelling surface fish with abundant access to nutrients. Cavefish have evolved altered blood sugar regulation, starvation tolerance, increased fat accumulation, and superior body condition. To investigate the genetic basis of cavefish metabolic evolution we carried out a quantitative trait loci (QTL) analysis in surface/cave F2 hybrids. We genetically mapped seven metabolism-associated traits in hybrids that were challenged with a nutrient restricted diet. Results: We found that female F2 hybrids are bigger than males and have a longer hindgut, bigger liver, and heavier gonad, even after correcting for fish size. Although there is no difference between male and female blood sugar level, we found that high blood sugar is associated with weight gain in females and lower body weight and fat level in males. We identified a significant QTL associated with 24-h-fasting blood glucose level with the same effect in males and females. Differently, we identified sex-independent and sex-dependent QTL associated with fish length, body condition, liver size, hindgut length, and gonad weight. We found that some of the genes within the metabolism QTL display evidence of non-neutral evolution and are likely to be under selection. Furthermore, we report predicted nonsynonymous changes to the cavefish coding sequence of these genes. Conclusions: Our study reveals previously unappreciated genomic regions associated with blood glucose regulation, body condition, gonad size, and internal organ morphology. In addition, we find an interaction between sex and metabolism-related traits in A. mexicanus. We reveal coding changes in genes that are likely under selection in the low-nutrient cave environment, leading to a better understanding of the genetic basis of metabolic evolution.

Original languageEnglish (US)
Article number94
JournalBMC Ecology
Issue number1
StatePublished - Dec 2021

Bibliographical note

Funding Information:
This work was supported by Grants from the National Institutes of Health [HD089934, DK108495]. Funding for genomic work was supported by NIH (1R01GM127872-01 to SEM, A. Keene, and N. Rohner). The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Publisher Copyright:
© 2021, The Author(s).


  • Astyanax mexicanus
  • Blood glucose
  • Body condition
  • Cavefish
  • Evolution
  • Gut
  • Liver
  • Metabolism
  • Quantitative trait loci
  • Sex
  • Teleost

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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