Genetically engineered Drosophila melanogaster larvae survive a toxic meal (Dr. M. Karageorgi)
The Whiteman Laboratory is part of the Department of Integrative Biology and Center for Computational Biology at the University of California, Berkeley. We use an interdisciplinary approach, involving behavior, biochemistry, chemical ecology, computational biology, evolution, genomics, molecular biology (including CRISPR-Cas9) and neuroscience to study the evolution of species interactions.
We (and many others) take the lead from Charles Darwin and Alfred Russell Wallace, who kept their focus on the evolution of traits arising from and shaped by biotic interactions. This is encapsulated in the famous 'tangled bank' metaphor (see below). We believe that traits shaped by the biotic environment are easier to study because their genomic architectures tend to be simpler than those shaped by the abiotic environment (see: https://bmcevolbiol.biomedcentral.com/articles/10.1186/1471-2148-11-60 and www.nature.com/articles/nrg1523). At the same time, it is clear that most adaptions are highly polygenic, and most genes are highly pleiotropic.
The main model systems we use include flies in the Drosophila lineage (including Scaptomyza spp. 'wasabi flies' to the right, figure to the right, courtesy, Dr. Marianthi Karagerogi) that attack the genetic model plant Arabidopsis thaliana and other glucosinolate-bearing plants (like canola and wasabi), insects specialized on cardenolide-bearing plants (like foxglove and milkweeds), creosote-feeding insects and broad-tailed hummingbirds. We focus on understanding (1) how free-living organisms evolve to become parasitic and specialized, (2) how hosts defend themselves against parasites, (3) and how species interactions drive specialization and the maintenance of functional genetic variation within species:
1. Evolution of parasitism: In the Scaptomyza system, which most people in our laboratory study, we focus on three barriers to colonization of living plants. The first of which is host finding and involves chemosensory evolution. Scaptomyza flies have lost canonical yeast-associated olfactory receptors and gained other receptors that facilitate finding the hosts plants on which their larvae can complete development (see this published chapter of the dissertation of Dr. Benjamin Goldman-Huertas). The second barrier is nutritional, which includes toxins, such as mustard oils. Scaptomyza flies have the most efficient glutathione S-transferase enzymes every discovered against mustard oils (see dissertation of Dr. Andrew Gloss).The third barrier is attachment to the host, which is accomplished in the species we study with a novel, cutting ovipositor used by female flies to scoop a hole into a leaf in which an egg is laid or leave exudate is consumed by her. These 'teeth' are derived from sensory bristles and have re-evolved in Drosophila suzukii and Scaptodrosophila spp. (see dissertation of Dr. Andrew Gloss).
2. Evolution of host defenses: We also study the interaction from the plant's point of view, as well as plant genome x parasite genome interactions. Specifically, we use diverse tools available for the model plant Arabidopsis thaliana and divergent populations, subspecies and species of Scaptomyza to dissect the genomic architecture associated with plant defense. Our most recent foray into this involves a GWAS in A. thaliana from wild accessions collected in Europe that had been genotyped using SNP arrays, and subsequently, whole-genome resequencing. We placed all of these plants in cages with two Scaptomyza populations, one from New England and the other from Arizona as herbivores, and we simply scored which plants were attacked and how much by ovipositing females. We stumbled on a locus in A. thaliana that explains a well-known, latitudinal cline in plant size across Europe, because the small plants escaped attack! We also found variation in the response of flies to variation in mustard oil pre-cursor genes--a plant genome x fly genome interaction. This work was collaborative research forming a chapter in Dr. Gloss' dissertation, is on the bioRxiv here and is also in revision after the first round of a helpful peer review at a journal: https://www.biorxiv.org/content/early/2017/06/27/156299
3. Evolution of specialization and maintenance of genetic diversity: It is a remarkable time in the field of evolutionary genomics (and therefore evolutionary biology). Richard Lewontin's and Jack Hubby's studies in Drosophila and Harry Harris's study on humans in the same year (1966) revealed far more genetic variation present within a species than anyone expected (summarized here). The neutral and nearly-neutral theories of molecular evolution flowed from this observation and have served (with renewed skepticism) as an important framework for studies of population genetics and molecular evolution. Think of them as null models (although it really isn't that simple). The central theme emerging from these theories is that standing (present levels of) genetic variation within natural populations is due to the balance between the rate of new mutations occurring and selection acting against them, with a strong influence from genetic drift. However, as Brian Charlesworth pointed out: "An important implication of the results described here is that they reject the hypothesis that variability in fitness components in Drosophila populations is maintained solely by a balance between the mutational input of deleterious variants and their elimination by selection. Instead, much of this variation appears to reflect the effects of some form of balancing selection or an interaction between migration and spatial variation in selection pressures." Around the time and subsequent to this statement, a handful of papers in the mid- to late-2000s that used experimental evolution or samples from natural populations found evidence that temporally and spatially varying natural selection may result in the maintenance of genome-wide variation in Drosophila. A study from Aneil Agrawal's group can be found here, here for one from Dmitri Petrov's group, here for one from Kimberly Hughes and John Kelly's groups, and here for one from Christian Schlötterer's group. Of particular note is the finding in several of these studies that alleles found at intermediate frequency in the ancestral or starting populationare those that responded to the agents of natural selection. This suggests that a heterogeneous environment, when coupled with random mating (e.g., gene flow), may cause functionally important genetic variation to be maintained at many loci over time, in natural populations. These studies are salient now because the neutralist-selectionist controversy has come full circle, written about in a brilliant way by Brian and Deborah Charlesworth here. Theodosius Dobzhansky studied Drosophila, particularly D. willistoni, in the context of adaptive polymorphism. In an expansive paper here, with Brasilian collaborators da Cuhna and Burla, they found that chromosomal variation in the form of inversion polymorphism, was correlated positively with habitat diversity (e.g., tree diversity) in Brasil. In particular, in the heart of the Amazonian rain forest, each female D. willistoni was heterozygous for different inversion polymorphism. This led them to claim: "We submit the workinghypothesisthat the amountof adaptivepolymorphism carried inapopulationtendstobeproportional to the varietyof habitats(ecological niches) which this populationexploits in a territoryit occupies." This claim was controversial and there were important problems with some of the specific ideas. Still, they were onto something. Dobzhansky saw the neutral theory through the lens (literally maybe) of abundant functionally important polymorphisms he had found in natural populations of Drosophila. He rejected the neutral theory as a result. However, the amount of balancing selection required to maintain the level of variation found in allonym studies was simply untenable. Howard Levene, who was a colleague of Dobzhansky's at Columbia University, formalized Dobzhansky et al.'s idea here (thankfully) into a mathematical model that resulted in many subsequent models (called the 'Levene Model'). It is important to point out the fact that Dobzhansky and Levene were at Columbia at the same time. Jeffrey Powell, here, completed a series of interesting experiments on Drosophila species in spatially varying and temporally fluctuating environments in the 1970s when limited allozymes were the genomic response variable. Trudy Mackay's Ph.D. dissertation, here, was also on this topic and highly relevant. There are many other examples, including E.B. Ford, of leaders in the field who worked on the maintenance of variation. Still, what is clear is that there is renewed interested in thinking about the relative roles of genetic drift and balancing selection in driving the maintenance of genetic variation in natural populations. Accounting for these two forces is a very challenging feat in practice and in theory. The problem, however thorny, is relevant to our research because herbivorous insects often are restricted in the range of host plants they use, but frequently can feed on many species in the same plant lineage. Is this 'oligophagy' simply due to phenotypic plasticity, or does balancing selection sensu Dobzhansky, Levene and the modern studies play a role? Our own unpublished experiments led by Dr. Gloss, in which Scaptomyza flava flies are evolved on single or mixed plant species or genotypes, have revealed the presence of a huge reservoir of functionally important genetic variation from, for example, a single population from a single field in Massachusetts. Levene and Dobzhansky both alluded to herbivorous insects and their host plants as ideal study systems for testing the Levene model. With our system we can manipulate the presence/absence of one gene in the host plant and study the effects of this single host gene on the evolution of the flies. We hope to help gain a clearer picture of the microevolutionary forces that shape natural populations and their evolutionary potential as a result of studies on a highly ecologically relevant system: over half of all insects share this life history, so insights from this one system may be a good model and therefore more generalizable, ab uno disce omnes. Ph.D. student Nicolas Alexandre is studying parallel questions in a population of the Broad-tailed hummingbird in Colorado, which exhibits a remarkable degree of within-population variation in bill traits we suspect is underpinned by balancing selection in a variable environment. Stay tuned for a genome sequence and GWAS. As part of a large collaboration, we are leading a study on the potential for balancing selection in maintenance of floral color polymorphism and a polymorphism in inducible indole glucosinolates in California radish, which is a hybrid swarm that replaced both parent species in nature!
Finally here is an inspiring quote from On the Origin of Species (1872) by Charles Darwin: "It is interesting to contemplate atangled bank, clothed with many plants of many kinds, with birds singing on the bushes, with various insects flitting about, and with worms crawling through the damp earth, and to reflect that these elaborately constructed forms, so different from each other, and dependent upon each other in so complex a manner, have all been produced by laws acting around us...Thus, from the war of nature, from famine and death, the most exalted object which we are capable of conceiving, namely, the production of the higher animals, directly follows. There is grandeur in this view of life, with its several powers, having been originally breathed by the Creator into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved."
Latest news from the Whiteman Laboratory: Noah was interviewed by UC Berkeley News of the Fiat Vox podcast: http://news.berkeley.edu/2018/07/03/podcast-growing-up-gay-in-rural-minnesota/
Ph.D. candidates Kirsten Verster and Tim O'Connor each received a summer research grant from the Department of Integrative Biology!
Ph.D candidate Tim O'Connor received another Philomathia fellowship to support his dissertation research next year. Congrats Tim!
We're getting close to submitting our ten-years-in-the-making genome paper on Scaptomyza flava and relatives. Stay tuned!
Noah was a co-chair of the 2018 Annual Drosophila Research Conference (of the Genetics Society of America) in Philadelphia, the next conference will be held in Dallas, Texas.
Ph.D. student Nicolas Alexandre received a grant from the David and Marvalee Wake Fund to support his work on broad-tailed hummingbird genomics.
Ph.D. student Julianne Pelaez received a Mentored Research Award from UC-Berkeley
Ph.D. student Julianne Pelaez received a 2018 Graduate Research Fellowship from the National Science Foundation to support her dissertation research on reproductive biology of drosophilid flies.
Former Ph.D. students Dr. Parris Humphrey and Dr. Andrew Gloss led a recent publication on habitat-associated evolutionary divergence in a plant driven by interactions with herbivores for a special issue on plant-herbivore interactions in Oecologia (PDF is found here).