Pmela and Tyrp1b contribute to melanophore variation in Mexican Cavefish

Abstract

Regressive evolution is a widespread phenomenon that affects every living organism, yet the mechanisms underlying trait loss remain largely unknown. Cave animals enable the study of degenerative disorders, owing to the frequent loss of eyes and pigmentation among lineages evolving in the subterranean habitat. Here, we utilize the blindMexican cavefish, Astyanax mexicanus, to investigate regressive loss of pigmentation because "ancestral" surface-dwelling morphs allow direct comparisons with cave-dwelling forms. Two genes (Oca2-albinism and Mc1r-brown) have been linked to specific pigmentation alterations in several cavefish populations. Pigment cell (melanophore) number is a complex trait governed by multiple genes, and variation in this trait may contribute to pigmentation diversity in Astyanax. To uncover genes associated with this trait, we assembled a high-resolution linkage map and used automated phenotypic scoring to quantify melanophore number variation across seven body regions in a surface × Pachón cave F 2 pedigree. QTL mapping yielded several markers strongly associated with melanophore number variation in the dorsal mid-lateral stripe area and superior head region, which anchor to regions of the Astyanax genome and the zebrafish genome. Within these syntenic regions, we identified two candidate genes, Tyrp1b and Pmela, with known roles in pigmentation based on gene ontology annotation. Mutant forms of these candidate genes in other organisms cause global and regional pigmentation variation, respectively. In Astyanax, these genes harbor coding sequence mutations and demonstrate differential expression in Pachón cavefish compared to surface morphs. In sum, this work identifies genes involved with complex aspects of Astyanax pigmentation and provides insight into genetic mechanisms governing regressive phenotypic change.