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

Abstract

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.

Convergence on reduced aggression through shared behavioral traits in multiple populations of Astyanax mexicanus

“…Further, identifying and functionally interrogating the genes that are contributing to the loss of aggression in A. mexicanus will provide additional insight into the genetic factors contributing to natural variation in aggression in this species. Methods such as QTL analysis and functional interrogation of candidate genes using CRISPR-Cas9 that are available in this species could be used in the future to answer these questions [28,[78][79][80]. This work provides a platform for investigating the extent to which heredity and/or environmental pressures inform the evolution of aggression across closely related populations in a same species.…”

Sex‐specific aging in animals: Perspective and future directions

“…Additionally, garter snakes with populations of fast‐ or slow‐aging snakes (at low and high altitude, respectively) show greater skew in male vs. female reproductive success in the fast‐aging populations and exhibit sex‐specific effects of a SNP in mitochondrial Cytochrome B on metabolic rate and aging/lifespan (Gangloff et al, 2020 ). Mexican cave fish ( Astyanax mexicanus ) are a particularly fascinating example of a species with a sex‐by‐habitat interaction in the evolution of metabolic traits (Riddle et al, 2021 ), but without sex‐specific or habitat‐specific lifespan (Riddle et al, 2018 ). Migratory species are also of interest, as there can be migratory and non‐migratory populations that experience vastly different environments and stresses, but still show similar levels of sex differences in aging and lifespan.…”

Genetic mapping of craniofacial traits in the Mexican tetra reveals loci associated with bite differences between cave and surface fish

“…We used a n=10 per population for sequence assessment. Population genomic metrics and analysis procedures are outlined in Riddle et al 2021. cDNA sequences were aligned using SnapGene (v6.1.2), from which fixed coding sequence changes were noted (Table 1).…”