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

Jaya Krishnan, Chris W. Seidel, Ning Zhang, Narendra Pratap Singh, Jake VanCampen, Robert Peuß, Shaolei Xiong, Alexander Kenzior, Hua Li, Joan W. Conaway, Nicolas Rohner

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Cis-regulatory changes are key drivers of adaptative evolution. However, their contribution to the metabolic adaptation of organisms is not well understood. Here, we used a unique vertebrate model, Astyanax mexicanus—different morphotypes of which survive in nutrient-rich surface and nutrient-deprived cave waters—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 (CREs) 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 CRE 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, and provides novel molecular insights into the evolutionary trade-off between loss of pigmentation and adaptation to food-deprived caves.

Original languageEnglish (US)
Pages (from-to)684-693
Number of pages10
JournalNature genetics
Volume54
Issue number5
DOIs
StatePublished - May 2022
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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