Payne, C. Y. | bioRxiv Science

bioRxiv2021

A Lethal Genetic Incompatibility between Naturally Hybridizing Species in Mitochondrial Complex I

The evolution of reproductive barriers is the first step in the formation of new species and can help us understand the diversification of life on Earth. These reproductive barriers often take the form of "hybrid incompatibilities," where alleles derived from two different species no longer interact properly in hybrids. Theory predicts that hybrid incompatibilities may be more likely to arise at rapidly evolving genes and that incompatibilities involving multiple genes should be common, but there has been sparse empirical data to evaluate these predictions. Here, we describe a mitonuclear incompatibility involving three genes in physical contact within respiratory Complex I in naturally hybridizing swordtail fish species. Individuals homozygous for specific mismatched protein combinations fail to complete embryonic development or die as juveniles, while those heterozygous for the incompatibility have reduced function of Complex I and unbalanced representation of parental alleles in the mitochondrial proteome. We find that the impacts of different genetic interactions on survival are non-additive, highlighting subtle complexity in the genetic architecture of hybrid incompatibilities. We document the evolutionary history of the genes involved, showing for the first time that an incompatibility has been transferred between species via hybridization. This work thus provides the first glimpse into the genetic architecture, physiological impacts, and evolutionary origin of a complex incompatibility impacting naturally hybridizing species.

evolutionary biology↗

bioRxiv2020

Pumiliotoxin metabolism and molecular physiology in a poison frog

Poison frogs bioaccumulate alkaloids for chemical defense from their arthropod diet. Although many alkaloids are accumulated without modification, some poison frog species can metabolize pumiliotoxin (PTX 251D) into the more potent allopumiliotoxin (aPTX 267A). Despite extensive research characterizing the chemical arsenal of poison frogs, the physiological mechanisms involved in the sequestration and metabolism of individual alkaloids remain unclear. We first performed a feeding experiment with the Dyeing poison frog (Dendrobates tinctorius) to ask if this species can metabolize PTX 251D into aPTX 267A and what gene expression changes are associated with PTX 251D exposure in the intestines, liver, and skin. We found that D. tinctorius can metabolize PTX 251D into aPTX 267A, and that PTX 251D exposure changed the expression level of genes involved in immune system function and small molecule metabolism and transport. To better understand the functional significance of these changes in gene expression, we then conducted a series of high-throughput screens to determine the molecular targets of PTX 251D and identify potential proteins responsible for metabolism of PTX 251D into aPTX 267A. Although screens of PTX 251D binding human voltage-gated ion channels and G-protein coupled receptors were inconclusive, we identified human CYP2D6 as a rapid metabolizer of PTX 251D in a cytochrome P450 screen. Furthermore, a CYP2D6-like gene had increased expression in the intestines of animals fed PTX, suggesting this protein may be involved in PTX metabolism. These results show that individual alkaloids can modify gene expression across tissues, including genes involved in alkaloid metabolism. More broadly, this work suggests that specific alkaloid classes in wild diets may induce physiological changes for targeted accumulation and metabolism.

physiology↗