Kimberly Frizzell, Ph.D.
Scientist at ARUP Laboratories
Graduate student at Cornell University
Junior Scientist at Tempus
High School Students
Scientist at Recursion Pharmaceuticals
Graduate student in Clark Lab
Graduate Student at University of California, San Diego
Graduate Student at University of Washington
WHAT WE STUDY
The Molecular Basis of Speciation
Speciation, the process by which one species splits into two, involves the evolution of reproductive isolating barriers such as the sterility or inviability of hybrids between previously interbreeding populations. Even in his masterpiece “On The Origin of Species”, Darwin could find no satisfactory solution to the apparent paradox of why natural selection would tolerate the onset of genetic barriers such as hybrid sterility and inviability that diminish the prospect of successful reproduction and, therefore, termed this problem the "mystery of mysteries".
The key to uncovering the molecular and evolutionary basis of speciation involves the identification of genes that cause hybrid sterility and inviability then find the molecular mechanisms of hybrid dysfunction from these genes. However, identification of genes that drive speciation represents an indispensable and rate limiting step even in the post-genomic era. Despite decades of intense efforts, very few such genes have been identified. Thus, we know even less about the evolutionary forces and the molecular developmental pathways that are disrupted in hybrids. Our lab specializes in identifying hybrid sterility and inviability genes in a variety of Drosophila species, such as the D. melanogaster, D. pseudoobscura and D. bipectinata groups of species. Current projects also involve developing genomics strategies to rapidly identify hybrid sterility and inviability genes and using cell biological approaches to understand the molecular basis of speciation.
Intra-Genomic Evolutionary Conflict
Genomes, instead of being static entities, are dynamic collectives of genes that are in evolutionary conflict with each other. For example, segregation distorters are selfish genetic elements that subvert the mechanisms of meiosis to over-represent themselves in gametes, thus gaining a massive evolutionary advantage. Segregation distorters enjoy their evolutionary advantage even when they impose a fitness cost on the individual carrying the distorter alleles, and thus represent a class of selfish elements. These fitness costs provide selection pressure for the evolution of genes that can suppress segregation distortion. However, successful suppression of distortion in turn puts back selection pressure on the distorter genes to evolve resistance to suppression. This continuing evolutionary arms race between segregation distorter genes and their suppressors can lead to the rapid evolution of the genes involved in this conflict.
These enigmatic selfish elements – which work by violating Mendel’s Laws – are ubiquitous in nature and are a potent evolutionary force in influencing the structures of genomes. Yet, almost nothing is known about their genic basis or molecular mechanism. We are interested in understanding how these elements subvert meiosis. These studies help us understand the evolutionary genetics of such conflicts and also shed light on the inner workings of the meiotic machinery. We are currently studying the molecular basis of segregation distortion in D. pseudoobscura Bogota-USAhybrids, and the SR system in D. pseudoobscura. Current projects also involve studying segregation distortion in very young species pairs where genetic conflict may have driven the evolution of hybrid sterility between species.
Causes and Effects of Positive Selection
Advances in whole-genome sequencing technologies and population genetic methods to detect selection in genome-wide studies have revealed several classes of genes that evolve rapidly under positive selection. While detecting signatures of selection at genomic locations has become easier, a detailed understanding of the evolutionary causes and the functional consequences of the rapid divergence of genes is still missing. Comparative genomics has revealed rapid evolution driven by positive selection in interesting classes of genes, e.g. genes involved in meiosis, nuclear transport, dosage compensation, RNA interference, etc., and we are interested in understanding the causes of rapid evolution at these genes, and the consequences of functional divergence.
While traditional approaches attempt the mapping of interesting phenotypes to genes, we instead use a reverse approach. While individual genes co-evolve with the internal genomic environment of their own species to maintain their function, there is no guarantee that these genes will function in the context of the genome of another species. We are interested in the functional analyses of genes that have evolved rapid sequence divergence under positive selection between D. melanogaster and its closest sister species D. simulans. Molecular analyses of non-complementing genes and the phenotypes revealed during inter-species swaps provide an exciting window into understanding the causes of positive selection at these genes and into uncovering the divergence of molecular functions of genes that evolve rapidly between species.