Our research questions all center on the origin and maintenance of biodiversity, across many levels of biological organization. I encourage you to visit the individual pages of researchers associated with my laboratory in order to understand the breadth and depth of our interests. Most researchers in my laboratory study interactions between a fly, a host plant, and their associated bacteria, but others focus on hummingbirds and their nectar plants, or creosote plants and associated insect communities. My own research program, which includes the interests and contributions of many of my students and postdoctoral mentees, is below. I provide quite a bit of detail because the topics are not particularly well-suited to brevity. An interesting feature of scientific research is that one often does not know the current research program of a laboratory by studying the publications that the laboratory has produced: this is because such studies are complete. So, I provide you below with my most current research interests, which are collaborative projects with my students.
Thanks for reading!
Dr. Noah K. Whiteman
The origin of new species, traits and the maintenance of functional genetic variation in populations
I study the origins and maintenance of biodiversity arising from species interactions. My research goal is to understand how these interactions lead to evolutionary change across all levels of biological organization. I use functional (ecological, behavioral, biochemical, morphological, neurological and physiological) and genomics (comparative, population, and quantitative) approaches to understand how species interactions drive organismal adaptation to the environment and lead to the spectacular radiations that fascinate and inspire biologists.
In addition to the projects discussed below, we have started new projects on the evolution of mistletoes, the microbiomes of mustard plants and S. flava, and on the genomic architecture associated with hummingbird bill length variation on floral architecture, in collaboration with Dr. David Inouye and Dr. Ethan Temeles. My research program is now very similar to that of Dobzhansky’s (e.g., Da Cunha et al. 1950, Evolution), although my focus is on antagonistic species interactions as potential drivers of adaptive phenotypes and new species, we also now study hummingbirds and their nectar plants. Dobzhansky’s work on flies and recent progress on plant and humans suggest that spatially varying selection (SVS) driven by species interactions play a critical role in shaping levels of polymorphism and divergence within species. Yet, we have few systems where these questions can be addressed experimentally in genomic model organisms. I have developed a new ecologically and genomically tractable host-parasite system to address such questions. My goal is to link agents of natural selection with targets of natural selection in the genomes of eukaryotic hosts and parasites. I am working to extend my research to human biology, particularly in relation to the role of parasites as selective agents and also how xenobiotic detoxification repertoires in humans have been shaped by interactions with plant toxins, and how this affects our physiology, particularly the aging process.
Consider, for example, that herbivorous insects and flowering plants compose >50% of all named species of life on Earth—a profusion of species that may be due, in large part, to antagonistic interactions (co-evolution) between these two lineages (Ehrlich & Raven 1964, Evolution). Can this process of co-diversification be boiled down to the origin, maintenance and loss of genetic polymorphism within species—and eventually to fixed differences that give rise to new species? Major catastrophic events, such as mass extinctions, as revealed in the fossil record, are also likely key to understanding the origin of adaptive radiations. Ultimately, I aim to use both microevolutionary and macroevolutionary approaches towards identifying the mechanisms driving the origins of plants and herbivorous insects, as well as the adaptive traits that underpin these extraordinary radiations of life. Dissecting the genomic basis of phenotypes arising from biotic interactions is likely to be more straightforward, for important reasons highlighted below than dissecting the genomic basis of phenotypes arising from interactions with the abiotic environment. In the case of host-parasite (e.g., plant-herbivorous insect) interactions, the agents of natural selection are other taxa rather than the abiotic environment. This distinction is important because several recent lines of evidence suggest that antagonistic species interactions are particularly salient agents of natural selection leading to adaptation and perhaps even reciprocal bouts of natural selection. Such studies can have broad implications: for examples does Fisher’s geometric or infinitesimal model better explain the genetic basis of adaptation?
In plants, quantitative trail loci associated with genes under positive natural selection from biotic interactions (biotic selection) are generally of larger effect size than genes under positive selection arising from abiotic factors (abiotic selection) (Louthan & Kay 2011, BMC Evol. Biol.). In humans, there is an analogous pattern arising from population genomic data: local pathogen diversity may be the most important driver of local adaptation across 55 human populations (Fumagalli et al. 2011, PLoS Genetics). Fundamental questions in evolution are therefore being addressed using traits mediated by host-parasite interactions, generating new insights and even more questions.
A closer look at the results from plants and humans suggests that macroparasites, herbivores in the case of plants and helminthes in the case of humans, may play a more important role than microparasites (viruses and bacteria) as agents of biotic selection. This pattern may arise from the fact that macroparasites tend to be longer lived and have higher prevalences than microparasites, providing the opportunity for chronic infections and long-term co-evolutionary interactions to unfold. Spatially varying and frequency dependent natural selection are likely the fundamental processes driving these patterns—the same phenomena that drove Dobzhansky’s research program. Notably, Dobzhansky advocated a strong role for balancing selection sensu lato in maintaining variation within natural populations. Howard Levene, who was a colleague of Dobzhansky’s at Columbia University, was among the first develop a theory allowing a test of the idea that the presence of multiple ecological niches can maintain alleles at equilibrium within a population. The role of positive selection, either through balancing selection or directional selection, in maintaining variation within populations or species is re-emerging as an important factor explaining the maintenance of genome-wide polymorphism in many species, in addition to the Neutral Theory and Nearly Neutral Theory of Molecular Evolution. Although controversial, this hypothesis is very exciting to me because host-parasite interactions are excellent systems in which to address these classic questions.
Many of the exciting results on biotic selection from plants and humans mentioned above rest on correlational evidence, rather than functional or experimental evolutionary evidence linked to data from natural populations. My specific research goal for this aim over the next 10 years is to focus on addressing this important gap in our knowledge. It is likely to be challenging and rewarding to pursue this question—the relative roles of stochastic and deterministic forces in shaping polymorphism and divergence within and between species continues to be a fundamental problem in evolutionary biology. The basis for these ideas was presented in our paper (Gloss et al. 2013, Curr. Opin. Plant Sci.) on the maintenance of genetic variation through plant-herbivore interactions.
To experimentally and functionally test the role of balancing selection sensu lato, I have focused my effort in the past six years at the University of Arizona and my latest efforts in my new position at the University of California, Berkeley, on developing a model host-parasite system that I believe could be used to address this gap in our knowledge. The herbivore is a drosophilid fly nested in the subgenus Drosophila (but called Scaptomyza flava) that lives as an endoparasite (leaf-miner) in the living leaves of mustard plants, including Arabidopsis thaliana and cannot be reared on any media. This species occurs naturally in Europe, North America and Asia. We now have an extremely high quality draft genome assembly. The goal of this research is to identify the role of biotic interactions in maintaining genome-wide polymorphism in experimental and natural populations. I am applying theoretically grounded population and quantitative genomics and divergence-based approaches to identify the targets of natural selection and the genomic bases of trait variation. Eventually I will measure the effect sizes of some of the alleles of interest and contribute to theory that develops a predictive framework for the evolution of genome architecture resulting from biotic selection. The guiding principle behind my work is embodied in the following from Ehrlich & Raven (1964, Evolution, page 606): “Indeed, the plant-herbivore ‘interface’ may be the major zone of interaction responsible for generating terrestrial organic diversity.” I suggest that this is a good starting point for considering whether this hypothesis can be extended to the origin and maintenance of adaptive divergence and polymorphism in plant and herbivore species that arises from these species interactions.
A striking feature of herbivorous insects is that 90% of all known species only utilize a narrow range of host plant species (termed oligophagy)—but most are not monophagous or polyphagous. This means that a single herbivore species typically attacks related and sympatric host plant species.
What is the genomic architecture underlying this complex phenotype? I use herbivorous insects and their host plants as models to test the question of how genetic polymorphism is potentially maintained by antagonistic interactions in natural populations. This approach uses population and quantitative genomics approaches, including evolve-and-resequence coupled with studies of natural populations (the latter are important because of problems associated with linkage disequilibrium and genetic drift in experimentally evolved populations). To address this question, we use the herbivorous drosophilid fly Scaptomyza flava for which we have a high-quality transcriptome and genome that we have sequenced, assembled and annotated in my laboratory. Herbivorous insects are excellent models for testing long-standing questions in molecular evolution. Dobzhansky (1951, Genetics and the Origin of Species) predicted that genetic polymorphism is maintained within populations of a species that inhabits diverse niches when no single allele is most fit across all niches. Levene (1953, Am. Nat.) created a mathematical model confirming this. Dobzhansky’s hypothesis resulted, in part, from his studies of the Amazonian Drosophila species D. willistoni, which exhibits an amazing diversity of chromosomal inversion variants within populations (Da Cunha et al. 1950, Evolution)—in some cases, each individual was heterozygous for unique inversions. Dobzhansky and colleagues proposed that because the Amazonian rainforest contains the world’s most diverse assemblage of angiosperms, spatially varying selection (SVS), generated by the diversity of rotting fruit substrates, maintained the diversity of inversion variants in D. willistoni. To link environmental and genetic variation, subsequent studies varied the laboratory-rearing environment for D. willistoni and other Drosophila species. Higher genetic variation persisted within populations in heterogeneous vs. homogeneous environments (e.g., Powell 1971, Science). However, these and others studies linked environmental variation to genetic variation within populations at only a few loci, so it remains unclear if genome-wide functional variation can be maintained in this way. If genome-wide variation were maintained in this way, it would challenge central tenets of the Neutral Theory of Molecular Evolution, which posits that the vast majority of polymorphisms segregating within populations are neutral, or nearly so, with respect to fitness.
Candidate species in which to test predictions of Dobzhansky and Levene’s model include Drosophila species that feed on microbes (e.g., D. melanogaster). However, the natural histories of many these species are notoriously difficult to assess. Oligophagous herbivorous insect species, on the other hand, and the stable habitats provided by their living host plants, are likely to provide us with the ability to easily identify the agents and targets of biotic selection and to manipulate these in the field and laboratory. In fact, these species were used as examples by Dobzhansky and Levene. The life histories of oligophagous herbivores, in which each co-occurring host plant species serves as a distinct habitat exerting unique selective pressures, is captured well by Levene’s model. SVS may be particularly salient in herbivorous insects—and could help explain their rapid rates of diversification and ability to quickly adapt to insecticides. Thus, oligophagous herbivores are excellent models for testing if environmental variation maintains genome- wide variation within populations.
The first experiment we are conducting (led by Ph.D. candidate Andrew Gloss) involves evolving flies on single or multiple host plant species, followed by evolve-and-resequence and population genomic analysis to identify signatures of directional and balancing selection. Notably, we are using genetically diverse germplasm of flies and plants from the field in these experiments. Such signatures can then be verified at the field sites in New England using population genomic analyses of S. flava larvae collected from the same host plant species in the wild. We are testing the hypothesis that fly populations evolved on mixed host plant cultures will exhibit genome-wide patterns of balancing selection.
The next component of this project focuses on using A. thaliana accessions and mutants as hosts because the herbivore we study, the leaf-mining drosophilid fly S. flava naturally attacks this model plant. Our collaboration, led by Andrew Gloss with Dr. Joy Bergelson and Dr. Ben Brachi at the University of Chicago, aims to identify the genomic regions within and among A. thaliana populations that are associated with resistance to attack by S. flava and to, in parallel, understand the evolutionary histories of these loci.
Eventually, we will be able to understand how variation in single or multiple host plant loci affects the maintenance of functional variation in S. flava using evolve-and-resequence studies like the ones above, except the host plants will vary at one or handful of loci. The eventual goal will be to identify genes in one organism and influence the evolution of genes in another, and vice versa. In parallel, we are initiating reciprocal natural selection experiments using a sexual species of Arabidopsis (A. lyrata) that are evolved in tandem with S. flava. At the end of the co-evolutionary experiment both species are subjected to pooled resequencing because a high quality genome assembly is available for both species. A question we are addressing with this system is how frequency-dependent reciprocal natural selection shapes the genomes of two interacting eukaryotes, as opposed to SVS.
Another research goal is to functionally confirm the role of the fly loci identified in the experimental evolution studies in detoxification and tolerance of plant defenses. Many candidate genes have been identified in response to glucosinolates (Whiteman et al. 2012; Gloss et al. 2014), and I will use these data to aid in identifying the subset of loci for validation. We are also using CRISPR-Cas9 genome editing in D. melanogaster and I would expect to apply this technology to the S. flava system as well in which we would swap alleles and isolate the fitness effects of particular alleles in different host plant environments. This will help address if balanced polymorphisms are functionally important in detoxification of plant defenses. We have been successful in linking organismal phenotypes with potentially adaptive genotypes, including individual amino acid substitutions in some cases (Gloss et al. 2014, Mol. Biol. Evol.). Linking these to fitness effects in nature is more difficult, but a goal is to eventually link variation in phenotype with genotype and fitness.
