Research
My research revolves around understanding two basic and intertwined phenomena in evolutionary biology: coevolution and convergent evolution. 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.
My work spans Vertebrate Evolution, here I highlight some systems that I have developed and am actively working in to answer BIG QUESTIONS about vertebrate evolution.
My work spans Vertebrate Evolution, here I highlight some systems that I have developed and am actively working in to answer BIG QUESTIONS about vertebrate evolution.
COEVOLUTION
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. To watch an interview about our collaboration with Scales of Biodiversity (Instituto Butantan, Brazil), click 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. To watch an interview about our collaboration with Scales of Biodiversity (Instituto Butantan, Brazil), click here.
Using an approach that combines phylogenetic inference with heterologous expression, 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. Read more about this work here. Or click here to see the International Toxin Talk.
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. Expanding this work we have found this mechanism of resistance has evolved independently at least 11 times in mammals! To learn more read this paper,
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. Expanding this work we have found this mechanism of resistance has evolved independently at least 11 times in mammals! To learn more read this paper,
WHAT CAN COEVOLUTION TEACH US ABOUT ADAPTATION?
While we often think about co-evolution as special cases of tightly intertwined species, in fact, most species on earth are responding to some degree of reciprocal selection pressure. Furthermore, marsupial diversity remains vastly understudied when compared to eutherian mammals. Gaining a better understanding of how coevolution influences the tempo, mode, and result of trait evolution in general can help us better understand the predictability of evolution. In my work I am interested in exploring:
While we often think about co-evolution as special cases of tightly intertwined species, in fact, most species on earth are responding to some degree of reciprocal selection pressure. Furthermore, marsupial diversity remains vastly understudied when compared to eutherian mammals. Gaining a better understanding of how coevolution influences the tempo, mode, and result of trait evolution in general can help us better understand the predictability of evolution. In my work I am interested in exploring:
- How do ecological interactions drive selection intensity ?
- Do both sides of a coevolutionary interaction follow the same evolutionary pace and mode?
- Do marsupials and eutherian mammals share the same capacity for trait evolution?
CONVERGENT EVOLUTION
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. Our most recent work using this dataset has revealed a key gene related to vision loss in both blind fish and mammals.
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. Our most recent work using this dataset has revealed a key gene related to vision loss in both blind fish and mammals.
Bears and other Hibernators
A new and exciting direction of research has emerged though a collaboration with the Iles lab in the University of Minnesota Department of Surgery. Using metabolomic data collected for Black Bears, the Iles lab has identified several key physiological changes that occur during hibernation. Using these data we have mined public genomic datasets to test for selection on key traits, as well as used cutting edge genomic datasets like the Zoonomia Project and Convergent Rate Analysis to make critical links between phenotype and genotype. Using the power of comparative genomics to examine the convergence of phenotypic and genotypic changes we have identified several key features of the hibernation phenotype, which are also being directly translated to both predictive diagnostics as well as therapeutics for human patients facing long term immobility.
A new and exciting direction of research has emerged though a collaboration with the Iles lab in the University of Minnesota Department of Surgery. Using metabolomic data collected for Black Bears, the Iles lab has identified several key physiological changes that occur during hibernation. Using these data we have mined public genomic datasets to test for selection on key traits, as well as used cutting edge genomic datasets like the Zoonomia Project and Convergent Rate Analysis to make critical links between phenotype and genotype. Using the power of comparative genomics to examine the convergence of phenotypic and genotypic changes we have identified several key features of the hibernation phenotype, which are also being directly translated to both predictive diagnostics as well as therapeutics for human patients facing long term immobility.
WHAT CAN CONVERGENCE TEACH US ABOUT ADAPTATION?
Convergent evolution has long been a focus of evolutionary biologists because it allows us a type of experimental model -- When you see a trait evolve twice independently, what parts are the same and what parts are different. More specifically with the advent of comparative genomic methods and the exponential rise of genomic data and methods, we have an unprecedented ability to examine how traits arise across very different genomes (from fish to humans!). Some exciting questions my work aims to address are:
Convergent evolution has long been a focus of evolutionary biologists because it allows us a type of experimental model -- When you see a trait evolve twice independently, what parts are the same and what parts are different. More specifically with the advent of comparative genomic methods and the exponential rise of genomic data and methods, we have an unprecedented ability to examine how traits arise across very different genomes (from fish to humans!). Some exciting questions my work aims to address are:
- What are the genes are repeated targets of adaptive evolution and why?
- How does genomic structure (gene and genome duplications, losses, and gene network structure) influence trait evolution?
- What role does positive selection play in gene losses or so-called 'regressive' evolution?
