Multiple trans QTL and one cis-regulatory deletion are associated with the differential expression of cone opsins in African cichlids

Abstract

Dissecting the genetic basis of phenotypic diversity is one of the fundamental goals in evolutionary biology. Despite growing evidence for gene expression divergence being responsible for the evolution of complex traits, knowledge about the proximate genetic causes underlying these traits is still limited. African cichlids have diverse visual systems, with different species expressing different combinations of seven cone opsin genes. Using opsin expression variation in African cichlids as a model for gene expression evolution, this study aims to investigate the genetic architecture of opsin expression divergence in this group. Results from a genome-wide linkage mapping on the F2 progeny of an intergeneric cross, between two species with differential opsin expression show that opsins in Lake Malawi cichlids are controlled by multiple quantitative trait loci (QTLs). Most of these QTLs are located in trans to the opsins except for one cis-QTL for SWS1 on LG17. A closer look at this major QTL revealed the presence of a 691 bp deletion in the promoter of the SWS1 opsin (located 751 bp upstream of the start site) that is associated with a decrease in its expression. Phylogenetic footprinting indicates that the region spanning the deletion harbors a microRNA miR-729 and a conserved non-coding element (CNE) that also occurs in zebrafish and other teleosts. This suggests that the deletion might contain ancestrally preserved regulators that have been tuned for SWS1 gene expression in Lake Malawi. While this deletion is not common, it does occur in several other species within the lake. Differential expression of cichlid opsins is associated with multiple overlapping QTL, with all but one in trans to the opsins they regulate. The one cis-acting factor is a deletion in the promoter of the SWS1 opsin, suggesting that ancestral polymorphic deletions may contribute to cichlid’s visual diversity. In addition to expanding our understanding of the molecular landscape of opsin expression in African cichlids, this study sheds light on the molecular mechanisms underlying phenotypic variation in natural populations.