Genome-wide analysis of cis-regulatory changes underlying metabolic adaptation of cavefish

Abstract

Cis-regulatory changes are key drivers of adaptative evolution. However, their contribution to metabolic adaptation of organisms is less understood. Here we have utilized a unique vertebrate model, Astyanax mexicanus , different morphotypes of which survive in nutrient-rich surface and nutrient-deprived cave water, to uncover gene regulatory networks underlying metabolic adaptation. We performed genome-wide epigenetic profiling in the liver tissues of Astyanax and found that many of the identified cis-regulatory elements have genetically diverged and have differential chromatin features between surface and cave morphotypes, while retaining remarkably similar regulatory signatures between independently derived cave populations. One such cis-regulatory element in the hpdb gene harbors a genomic deletion in cavefish that abolishes IRF2 repressor binding and derepresses enhancer activity in reporter assays. Selection of this mutation in multiple independent cave populations supports its importance in cave adaptation, providing novel molecular insights into the evolutionary trade-off between loss of pigmentation and adaptation to food-deprived caves.

The metabolome of Mexican cavefish shows a convergent signature highlighting sugar, antioxidant, and Ageing-Related metabolites

“…Finally, cholesteryl esters and cholesterol in some feeding states (Table Supplementary file 1 ), were less abundant in cave populations. Using a previously published gene expression dataset ( Krishnan et al, 2022 ), we investigated factors that might influence levels of cholesteryl esters. Cholesteryl ester transfer protein (CETP), which transports cholesterol in / out of lipoproteins, is downregulated in both Pachón and Tinaja compared to surface fish ( Figure 7—figure supplement 5 ), suggesting a potential causal relationship between lower cholesteryl ester levels in cave populations and this important carrier protein.…”

“… Previously published RNA-Seq data ( Krishnan et al, 2022 ) of CETP (ENSAMXG00000003656) and HMGCRA/B (ENSAMXG00000007971 /ENSAMXG00000016175) in cave / surface A. mexicanus . Values on the y-axis are gene expression data in terms of counts measured in liver tissue under normal feeding conditions.…”

Evolution of the regulation of developmental gene expression in blind Mexican cavefish

“…Looking at changes in gene regulation is critical to understand how species evolve and adapt to their environment. The contribution of cis -versus trans -regulation to the process is increasingly studied in animals and plants [4, 5, 20-22, 38, 39]. To our knowledge, this work is the first to examine transcriptome-wide the regulatory changes occurring during early developmental evolution in a teleost.…”

“…Teleost fish are the most diversified vertebrate group with more than 30,000 species adapted to various environments and displaying a wide range of morphologies [3]. However little is known on the genome-wide regulatory evolution accompanying their diversification [4, 5]. The Mexican tetra, Astyanax mexicanus , has emerged as a model to study microevolution and adaptation to a drastic environmental change.…”

“…Teleost fish are the most diversified vertebrate group with more than 30,000 species adapted to various environments and displaying a wide range of morphologies [3]. However little is known on the genome-wide regulatory evolution accompanying their diversification [4,5].…”