Research
My research revolves around understanding two basic and intertwined phenomena in evolutionary biology: coevolution and convergent evolution. Though the study of coevolutionary relationships has been a focal point of evolutionary biology, demonstrating a truly reciprocally evolving interaction at the molecular and functional level in an empirical system has remained elusive. Coevolutionary interactions often span speciation events, or are present in repeated paired associations across disparate species, and thus represent ideal system in which to examine repeated evolution. My work leverages these qualities to examine the genetic, historical, and biophysical basis of extraordinary repeated and coevolutionary adaptations.
Opossums and Vipers
Members of the South American marsupial family Didelphidae are not only resistant to snake venom but also attack and eat pit-vipers with impunity, exhibiting no behavioral precautions while subduing these dangerous snakes. In particular, several members of this tribe are known to prey upon Bothrops jararaca, a South American pit viper. Bothrops jararaca venom is known to contain a C-type-lectin (CTL) protein, Botrocetin, which specifically targets the mammalian blood protein vWF (von Willebrand factor), and causes excessive systemic bleeding. My research has revealed that large and some small bodied opossums have evolved vWF which is resistant to coagulation disruption by these and similar venom CTLs. Read more about this work here.
Opossums and Vipers
Members of the South American marsupial family Didelphidae are not only resistant to snake venom but also attack and eat pit-vipers with impunity, exhibiting no behavioral precautions while subduing these dangerous snakes. In particular, several members of this tribe are known to prey upon Bothrops jararaca, a South American pit viper. Bothrops jararaca venom is known to contain a C-type-lectin (CTL) protein, Botrocetin, which specifically targets the mammalian blood protein vWF (von Willebrand factor), and causes excessive systemic bleeding. My research has revealed that large and some small bodied opossums have evolved vWF which is resistant to coagulation disruption by these and similar venom CTLs. Read more about this work here.
Using an approach with combines phylogenetic inference with heterologous expression and biophysical assays, I have reconstructed hypothetical ancestral vWF across this clade of opossums and tested their function against several venom derived CTL proteins. This work has revealed patterns of adaptation and coevolution in opossum vWF across an ~20 million year history. With recent advances in genomic and proteomics of snake venom, this system is uniquely poised to explicitly test the functional and molecular evolution of both interacting partners in a coevolutionary relationship.
Photo credit: Fort Wayne Children's Zoo
Honey Badgers and Cobras
The Honey Badger (Mellivora capensis) is an African mustelid which is also known to regularly prey upon venomous snakes, in particular, the Cape Cobra. These snakes are known to contain venom with potent neurotoxins, called alpha-neurotoxins. The muscular nicotinic acytlecholine receptor (nACHr) is targeted by these alpha-neurotoxins. Some mammals have evolved venom-resistant nAChRs that no longer bind these toxins. Using a comparative phylogenetic analysis of mammalian nAChR sequences, we found that honey badgers, hedgehogs, and pigs have independently acquired functionally equivalent amino acid replacements in the toxin-binding site of this receptor. In venom-resistant mongooses, different replacements are present at these same sites but prevent toxin binding through a different mechanism. Read more about our findings here. Currently we are expanding this system to look at the evolution of the nAChR receptor across several mammalian species that are known to interact with alpha-neurotoxin producing snakes.
The Honey Badger (Mellivora capensis) is an African mustelid which is also known to regularly prey upon venomous snakes, in particular, the Cape Cobra. These snakes are known to contain venom with potent neurotoxins, called alpha-neurotoxins. The muscular nicotinic acytlecholine receptor (nACHr) is targeted by these alpha-neurotoxins. Some mammals have evolved venom-resistant nAChRs that no longer bind these toxins. Using a comparative phylogenetic analysis of mammalian nAChR sequences, we found that honey badgers, hedgehogs, and pigs have independently acquired functionally equivalent amino acid replacements in the toxin-binding site of this receptor. In venom-resistant mongooses, different replacements are present at these same sites but prevent toxin binding through a different mechanism. Read more about our findings here. Currently we are expanding this system to look at the evolution of the nAChR receptor across several mammalian species that are known to interact with alpha-neurotoxin producing snakes.
Cavefish
Convergent evolution, species’ ability to repeatedly invade and adapt to similar environments, has offered insight into the ways that diverse organisms evolved to cope with similar selective pressures. Studies of widespread convergence have been central to pinpointing the genetic mechanisms of adaptation and have revealed that phenotypic convergence can be a result of completely independent genetic mechanisms, changes in the same gene but at different sites, different changes at the same sites, or rarely, complete genetic convergence with the same changes at the same sites. The spread of these scenarios inform the level of constraint involved in the evolutionary process. These insights into the function, constraints, and diversity of genes across species add to our basic understanding of how genes evolve and relate to phenotypes, and contributes fundamentally to our understanding of human genetics, behavior, and disease.
Using a comparative genomic approach, and several newly sequenced cavefish genomes, we aim to identifying genes evolving at convergent rates in >15 divergent cavefish lineage. We are employing new bioinformatic tools which leverage evolutionary rate-convergence and have the potential to reveal genes evolving under positive selection, gene losses, and increased constraint which contribute to the cave dwelling condition.
Convergent evolution, species’ ability to repeatedly invade and adapt to similar environments, has offered insight into the ways that diverse organisms evolved to cope with similar selective pressures. Studies of widespread convergence have been central to pinpointing the genetic mechanisms of adaptation and have revealed that phenotypic convergence can be a result of completely independent genetic mechanisms, changes in the same gene but at different sites, different changes at the same sites, or rarely, complete genetic convergence with the same changes at the same sites. The spread of these scenarios inform the level of constraint involved in the evolutionary process. These insights into the function, constraints, and diversity of genes across species add to our basic understanding of how genes evolve and relate to phenotypes, and contributes fundamentally to our understanding of human genetics, behavior, and disease.
Using a comparative genomic approach, and several newly sequenced cavefish genomes, we aim to identifying genes evolving at convergent rates in >15 divergent cavefish lineage. We are employing new bioinformatic tools which leverage evolutionary rate-convergence and have the potential to reveal genes evolving under positive selection, gene losses, and increased constraint which contribute to the cave dwelling condition.
