As a graduate student in Katie Peichel's lab (2002-2008), my dissertation research comprised genetic, sequence, and cytogenetic characterizations of the young sex chromosome systems and sex determination mechanisms found in several species of stickleback fish, particularly the threespine stickleback, Gasterosteus aculeatus. My experiences in Katie's lab solidified my interest in continuing to use a comparative method to understand the genetic basis of developmental change.
As a post-doctoral scientist, I chose to move from stickleback fish to a model species, the nematode Caenorhabditis briggsae. This relative of the more famous C. elegans is useful to biologists for a number of reasons. In particular, although it is a globally distributed species like C. elegans, C. briggsae wild isolates exhibit much more genetic and phenotypic diversity. This natural variation makes C. briggsae ideal for the study of evolutionary genetics and development. In addition, C. briggsae shares many of the characteristics that makes C. elegans a model species for genetics:
Part of our research group seeks to understand how genetic changes (mutations) cause parents to have unhealthy (sterile or dead) offspring. More broadly, this is called the study of species formation. To study this question, we use microscopic worms (like C. elegans) and tools like measuring the fitness of parents, then mating them, measuring the health of their offspring, and extracting and analyzing DNA of healthy and unhealthy worms to find the regions of their chromosomes that contain fitness-reducing mutations. Recently, some projects in the lab have focused on our prior result that some offspring have dysfunctional mitochondria, and future questions we hope to study include: a) what aspects of mitochondrial biology are not functioning properly? b) does reduced mitochondrial function cause slow development? c) do these unfit worms consume less oxygen (a potential collaboration with Dr. Dejean in the Department of Chemistry)? Another line of inquiry involves mitochondrial inheritance. Normally, animals inherit all of their mitochondria only from their mothers, but we have found that our worms occasionally inherit some mitochondria from their father. We have positions (perhaps paid) to study the mechanisms that enable these weird worms to avoid inheriting mitochondria solely from their mothers. A third broad question to be addressed seeks to identify genetic differences between different populations of our worms (e.g. from India, Japan, Ohio, Kenya) that help them adapt to life at different temperatures. The broad outcome of this type of project is to better understand the extent to which genetics can limit the ability of natural populations to withstand climate change. Another set of projects in the lab relates to Scott Baird's discovery that some inter-population hybrids develop more slowly than others, which suggests that a genetic incompatibility within this worm species can impact fitness.
An absolute loss of hybrid fitness (hybrid inviability or infertility) defines biological species: populations that are unable to produce viable or fertile hybrid offspring. Undoubtedly, a continuum of such hybrid dysfunction phenotypes parallels the continuum of genetic divergence that can exist between populations. Fitness effects might range from inviability and infertility to an almost imperceptible loss of fitness in hybrids between populations that have only barely begun to genetically diverge. A key challenge in understanding how speciation is initiated is the empirical identification of naturally occurring inter-population genetic incompatibilities that have a minor effect on hybrid fitness.
We have identified the genetic signatures of inter-population genetic incompatibilities in AF16-HK104 hybrids. In one case, hybrids with the HK104 mitochondrial haplotype are significantly more likely also to have HK104 alleles in one region of one autosome. This correlation of nuclear and mitochondrial genotypes suggests that certain combinations of mitochondrial and nuclear alleles are unfit and selected against.
The rationale for the interdependence of mitochondrial and nuclear genomes is clear: both genomes encode proteins that physically interact to form mitochondrial electron transport complexes. Thus, sequence variation in a mitochondrial gene might demand that a compensatory nuclear mutation exist in order to maintain electron transport efficiency. Indeed, the separation of co-adapted mito-nuclear gene complexes during the formation of hybrids has been suggested to result in mitochondrial dysfunction in a handful of taxa. The fitness effects of such hybrid genetic incompatibilities likely result from decreased ATP production.
These hypotheses suggest a specific experimental approach: establishing genetic crosses to assess the effect of mitochondrial genotype on hybrid fitness. Phenotyping such hybrids for mitochondrial and life history traits should reveal whether genotype influences phenotype, facilitating a mapping approach to identify the specific nuclear and mitochondrial loci involved. Crosses between additional pairs of wild isolates are being undertaken to identify the extent of incompatibilities between strains of the species.
It is rare to discover cases representing the early stages of an evolutionary process, and I am capitalizing on my empirical identification of a hybrid mito-nuclear incompatibility between two wild strains of the same species. My proximal research goal is to use C. briggsae to understand the mechanisms and genetic architecture of incompatibilities arising between two populations. Investigations of mito-nuclear incompatibility in the C. briggsae model system promise to inform us about how nuclear and mitochondrial genomes co-evolve to maintain fitness and how disrupting those co-adapted gene complexes might lead to hybrid dysfunction.
The research goals for the study of intra-species hybrid incompatibilities are to: