Collaborative Research: EDGE CMT: Genetic and energetic basis of mitonuclear incompatibilities during speciation

Stanford University, Stanford CA

Investigators

Abstract

How new species are formed is a grand challenge across biology. Particular combinations of genes from different populations may not interact favorably during hybridization, creating unhealthy offspring due to genetic incompatibilities. The specific genes involved in this process are seldom identified, but genes involved in mitochondrial function are prime candidates and the focus of recent research. This project will investigate how different combinations of mitochondrial and nuclear genes create reproductive barriers in hybridizing swordtail fish (Xiphophorus), a model system for genetic incompatibilities. Genomic tools will be used to identify which specific combinations of nuclear and mitochondrial genes influence overall hybrid health. Specific aspects of mitochondrial function such as respiratory efficiency will also be investigated as a mechanistic basis for hybrid incompatibilities. Genetic incompatibilities will also be investigated in different environments and developmental stages because incompatibilities may only manifest in certain conditions. This work includes generating hybrids in the laboratory by targeted crossing experiments and examining natural populations with ongoing hybridization. These activities will be used to recruit students from diverse backgrounds to STEM research, especially in the opportunity-rich field of bioinformatics. Freshmen will be explicitly targeted though the development of a new program called “Power in the Powerhouses” as part of the University of Texas at Austin’s highly successful Freshman Research Initiative to recruit and train the next generation of STEM researchers. Coevolution between nuclear and cytoplasmic genomes can create coadapted genomes within a population that may be disrupted during hybridization, creating reproductive isolation and acting as a common mechanism of speciation. Under this hypothesis, selection during introgressive hybridization should act to maintain coadapted cytonuclear genotypes. To test this hypothesis, genome-wide patterns of ancestry will be generated from three naturally hybridizing pairs and three lab-generated hybrid pairs of swordtail fish species (genus Xiphophorus). Selection should especially favor matched ancestry between mitochondrial genomes and the subset of nuclear-encoded genes that interact with mitochondrial-encoded gene products. Mitonuclear incompatibilities will be identified through statistical associations between nuclear alleles and mitotypes in natural and lab-bred hybrids. Lethal mitonuclear incompatibilities have already been identified using this approach in one pair of hybridizing Xiphophorus. Mitochondrial- and nuclear-interacting genes should also show concordant clines in ancestry with geography. Compromised energetic phenotypes as well as reduced organismal fitness should result from incompatible combinations of mitochondrial and nuclear genes, likely in an environmentally-dependent context. Therefore, in addition to standard metrics of organismal health, whole-organism metabolic rates and mitochondrial DNA copy number will be assessed in parental Xiphophorus species and their hybrids in response to thermal and hypoxic stressors. Multiple respiratory phenotypes in isolated mitochondria will also be investigated, including those dependent on mitonuclear interactions. Phenotypes will be assessed in adults and embryos, as lethal mitonuclear incompatibilities can prevent embryos from developing. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.