The James F. Crow Early Career Researcher Award recognizes outstanding achievements by students and recent PhDs presenting their work at the Population, Evolutionary, and Quantitative Genetics (PEQG) Conference, which was part of TAGC Online in 2020. The 2020 winner and finalists for this prestigious PEQG award spoke in a high-profile session at the conference. Check out the recording below!

Winner

Carl Veller, Harvard University 

Finalists

The recipient of the 2018 Crow Award reveals details of flu evolution at the smallest —and largest—scales.

For many viral diseases, a vaccine can provide lifelong protection. But for flu, you need a new shot every year. The influenza virus evolves so fast it presents a constantly moving target for both our immune systems and public health authorities, fueling epidemics like the particularly bad season we just endured. With over 30,000 people hospitalized in the United States alone this season, the flu provides a dramatic reminder of the importance of understanding evolutionary dynamics.

Katherine Xue, a graduate student at the University of Washington, is revealing the mechanics of influenza evolution on scales ranging from an individual person up to the entire planet. Xue was awarded the 2018 James F. Crow Award for Early Career Researchers for her doctoral work on the subject after a presentation at the Population, Evolutionary, and Quantitative Genetics Conference in May.

In a special session of talks by Crow Award finalists, Xue spoke about using deep sequencing to examine diversity in flu virus populations.

“Up until recently, we were only able to look at the average genetic identity across the millions or billions of flu viruses in a single infection,” says Xue. “We’ve used deep sequencing to show that within a single infection there are fast evolutionary dynamics that have been invisible to previous technologies.”

Xue approaches clinical topics with the conceptual tools developed by evolutionary and population geneticists. Linking ideas across fields is characteristic of Xue, says her mentor Jesse Bloom (Fred Hutchinson Cancer Research Center / University of Washington), whether it’s between medicine and evolutionary theory or between science and the humanities.

“What makes Katherine stand out is her ability to think about big scientific concepts and connect ideas,” says Bloom. “She’ll see and connect ideas in ways that I can’t.”

Viral cooperation

When Xue first rotated in Bloom’s lab, she was working on a molecular virology project about how a particular viral protein binds to a cell. In the course of examining sequence databases, she noticed the mutation she was studying was often ambiguously annotated.

Inspired by this hint of population diversity, she wondered whether the two viral variants might interact with each other. She was able to establish that the mutation tended to occur alongside the wild type version within a population; the mutation was deleterious to virus reproduction on its own but beneficial when mixed with wild-type. This example of cooperation suggests that interactions between different variants within flu populations can be important factors in virus evolution.

A glimpse of evolution in action

But can evolution be detected within the virus population of a single individual? Xue was drawn to the question of how global flu evolution traces back to the founding infections in which each mutation must first arise.

“I was intrigued because it was hard to imagine how this works,” says Xue. “Flu infections are very short; there’s not a lot of time for a new mutation to reach frequencies large enough to ensure it makes it over to the next infected person.” In the language of population geneticists, flu populations are repeatedly subjected to extreme bottlenecks. But observing such rapid evolution in action is extremely challenging.

Xue and her colleagues in the Bloom lab used a unique approach to get around this problem. They partnered with clinicians Michael Boeckh and Steve Pergam at the Fred Hutchinson Cancer Research Center, who had collected samples from four immunocompromised patients over the course of their months-long flu infections. Deep sequencing these samples gave them an in-depth view of a process that would normally be finished within days in a person with healthy immune defenses.

“I initially had doubts that this project would show us anything interesting or be worth doing,” says Bloom. “But Katherine is very independent and persistent, and she kept going despite my occasional words of discouragement.”

The results were dramatic. Over the span of about two months, there was a substantial amount of flu evolution within each patient. Mutations arose regularly, fluctuated in frequency, and even became fixed in the population in a few cases. They also saw evidence that some of these changes are due to selection. The same mutations would often arise independently and then rise to substantial frequencies in multiple patients, suggesting these particular changes were adaptive.

Remarkably, the mutations that arose repeatedly in different patients were sometimes the same mutations that spread through the global flu population within the next decade. The immunocompromised patients seemed to be microcosms of global evolutionary patterns. “We were astonished,” said Xue.

Most of these recurring mutations affect the part of the flu haemagglutinin protein that is most recognized by the host immune system, so the team hypothesizes that the changes help the flu escape host defenses.

These results raise many questions about how evolutionary dynamics interact across scales. How far do the conclusions generalize? Where and when do natural selection and genetic drift act? How do normal week-long infections generate enough diversity to fuel rapid global evolution? Could understanding these processes translate to better flu season predictions? Xue’s graduate research continues to explore flu evolution with these questions in mind.

Connecting ideas

The scientific big picture is never far from Xue’s mind, it seems. Alongside her thesis research, Xue is pursuing a certificate in science and technology studies, with a capstone project on the history of flu research. “I have really loved being part of the history, philosophy, and sociology of science community here,” she says. “It’s given me a lot of perspective that has been really enriching.”

A few years ago Xue helped start the UW Genomics Salon, which is a group of students and postdocs who take part in freeform discussions about the intersections of science and society. These discussions touch on policy, advocacy, communication, education, representation, law, art, and a host of other topics.

Bloom thinks Xue’s broad interests are yet another reflection of her creativity and ability to link ideas across fields. Before graduate school, she spent a few years working as a science writer for the Harvard Magazine. “She’s an exceptionally good science communicator and very dedicated to creating connections between science and other fields. It’s pretty awesome to have someone like that around!”

[youtube https://youtu.be/fTdaAwqdt0k&w=500&rel=0]

Watch #PEQG18 presentations from all the other  outstanding finalists for the Crow Award here.

Watch presentations from the conference, including talks from Katie Peichel and Jonathan Pritchard.

Now that the dust has settled from the whirlwind of the first ever standalone GSA Population, Evolutionary, and Quantitative Genetics Conference (PEQG18), we’re delighted to be able to share the audio and synched slides from the Keynote and Crow Award sessions.

We’re gratified too that attendees got so much of value from the conference. Many have approached GSA staff and the conference organizers with rave reviews of their experience, and, despite the usual growing pains of a new conference, the results from the attendee survey have also been overwhelmingly positive.

We’re excited to incorporate some of the lessons we’ve learned into planning the next PEQG. It will be held April 22–26, 2020 in the metro Washington, DC, area at The Allied Genetics Conference (TAGC20). PEQG will join the C. elegans, Drosophila, mouse, Xenopus, yeast, and zebrafish research communities for a mix of community-specific and cross-community sessions.

Stay tuned for more announcements on the upcoming conference and for several more PEQG18 blog reports in the coming weeks. Enjoy the talks below!

PEQG18 Keynotes

Jonathan Pritchard Stanford University/HHMI

Omnigenic Architecture of Human Complex Traits

Catherine Peichel University of Bern

Genetics of Adaptation in Sticklebacks

Trudy Mackay North Carolina State University

Context-Dependent Effects of Alleles Affecting Genetic Variation of Quantitative Traits COMING SOON

Finalists for the 2018 Crow Award for Early Career Researchers

Amy Goldberg UC Berkeley

A mechanistic model of assortative mating in a hybrid population

Emily Josephs UC Davis

Detecting polygenic adaptation in maize

Jeremy Berg Columbia University 

Population genetic models for highly polygenic disease

Katherine Xue University of Washington 

Evolutionary dynamics of influenza across spatiotemporal scales

Alison Feder Stanford University 

Intra-patient evolutionary dynamics of HIV drug resistance evolution in time and space

Emily Moore North Carolina State University 

Genetic variation at a conserved non-coding element contributes to microhabitat-associated behavioral differentiation in Malawi African cichlid fishes

Videos

Jonathan Pritchard 

[youtube https://youtu.be/H18k55ruCOY&w=500&rel=0]

Catherine Peichel

[youtube https://youtu.be/QRCcLixjUtc&w=500&rel=0]

Amy Goldberg 

[youtube https://youtu.be/kccUNkF7SgY&w=500&rel=0]

Emily Josephs 

[youtube https://youtu.be/CxQOrK9h6D4&w=500&rel=0]

Jeremy Berg

[youtube https://youtu.be/HqA1H24LPZc&w=500&rel=0]

Katherine Xue

[youtube https://youtu.be/fTdaAwqdt0k&w=500&rel=0]

Alison Feder

[youtube https://youtu.be/ntM0448h2lA&w=500&rel=0]

Emily Moore

[youtube https://youtu.be/aX4_HS0K1kA&w=500&rel=0]

We are delighted to announce the finalists for the James F. Crow Early Career Researcher Award! All finalists will speak at the Crow Award session of the Population, Evolutionary, and Quantitative Genetics Conference on May 14, 2018 in Madison, Wisconsin.

The Award honors the legacy of James F. Crow, whose contributions to the field of genetics were impactful and innumerable. Learn more about Crow and the award.

Crow Award finalists: Top row, left-right: Jeremy Berg, Alison Feder, Amy Goldberg; bottom row, left-right: Emily Josephs, Emily Moore, Katherine Xue

Jeremy Berg

Columbia University

I have always been interested in how things work. As a child, this manifested first as an interest in understanding how various pieces of machinery worked, and later in the laws of physics and cosmology. As an undergraduate student at the University of Wisconsin (where I was fortunate enough to have Crow as a guest lecturer a few years before his death), my interests turned toward the biological, and particularly to evolution. It seems natural then that I was drawn to population genetics, as it is the science which deals on a mechanistic level with understanding how the evolutionary process works, and I chose to pursue a PhD in this area at UC Davis.

In particular, my work focuses on understanding how evolutionary processes played out over the past ~200,000 years have contributed to the generation of diversity within the human population. Sometimes, this takes the form of understanding recent adaptations that have evolved within human populations, which gives us an insight into the challenges that our ancestors faced and the kind of traits that helped them survive and prosper. Another branch of my work focused more on the role of evolution in genetic disease, and in particular understanding why certain genetic diseases persist in the population despite their obvious fitness costs, and what forces are respsonsible for shaping their underlying genetic architectures.

Go to Jeremy Berg’s presentation abstract.

Alison F. Feder

Stanford University

I loved both math and life sciences classes throughout school, so when I started college, I sought out a research experience in quantitative biology. This search led me to Warren Ewens and Joshua Plotkin, who showed me how quantitative approaches could be especially instructive in understanding evolutionary biology. For example, when a population changes over time, can we use statistics to determine whether chance or selection drives those changes? This research question, which I pursued in Dr. Plotkin’s lab as an undergraduate, seeded a longstanding interest in understanding adaptation quantitatively.

I want to understand how and when populations adapt in the face of daunting evolutionary odds. Whereas most empirical and theoretical work has considered populations evolving to a single challenge, in nature, these challenges often are multiple and sometimes orthogonal. For example, we currently treat HIV with combinations of three drugs that attack different stages of the viral life cycle. This treatment strategy has substantially reduced but, importantly, not eliminated, the evolution of drug resistance within patients. How does adaptation still occur under such improbable conditions? I use HIV as a case study to understand evolution to selective pressures of varying complexity, including those structured in physical space. Many natural and man-made environments present similarly difficult challenges to species in nature. What separates the conditions that allow some species to persist via adaptation but drive others to extinction? Long-term, I hope to address such questions in a way that both improves human health and advances our fundamental understanding of evolution.

Go to Alison Feder’s presentation abstract.

Amy Goldberg

University of California, Berkeley

The recent availability of large high-coverage genetic datasets, combined with careful ecological sampling, has demonstrated the outsized impact that recent evolutionary history—the last tens of generations—can have on the genetic and phenotypic variation of a population. I develop quantitative methods to elucidate recent population histories, and interpret these histories in the context of demographic, cultural, and environmental pressures. Starting my scientific career with archaeological fields schools, my strong interest in mathematics and a desire to quantitatively test hypotheses drew me to population genetics.

Admixture, or hybridization, is one of the fastest evolutionary processes to radically change the composition of a population. Admixed populations are formed through the exchange of individuals from two or more previously isolated populations. Acting as a natural experiment, admixed populations offer insight into adaptations of their parental populations, and are ubiquitous throughout animal and plant populations. Multiple processes such as inbreeding avoidance and phenotypic mate preferences direct how parental populations mix. Despite this complexity, previous methods often considered admixed populations as simple instantaneous combinations of their sources. Instead, my work takes a mechanistic approach, deriving flexible sets of mathematical models to consider the admixture process, which often varies in intensity geographically or over time. Importantly, my theoretical results demonstrate that previous work—which does not consider sex bias, nonrandom mating, or the mechanistic process—misestimates population history parameters, such as the timing and intensity of migration. My work also links admixture dynamics with classic population genetic models of breeding and assortative mating by genotype.

Go to Amy Goldberg’s presentation abstract.

Emily B. Josephs

University of California, Davis

I was always interested in being some sort of scientist and experiences volunteering at a small aquarium, along with taking an conservation biology class in high school, fostered that interest. However, it was in my first evolutionary biology class, when I discovered population genetics, that I got excited about evolutionary biology. This enthusiasm led me to a research assistant position in an evolutionary ecology lab, where I got to participate in the often-tedious-but-occasionally-exciting business of actual science. After graduation, I worked as a technician studying speciation in wild tomatoes and rapid adaptation in Trinidadian guppies before starting graduate school at the University of Toronto. I spent my PhD trying to disentangle how selection and drive shape genetic variation in the weedy plant species Capsella grandiflora. I found that negative selection against new mutations and positive selection for new mutations shape broad patterns of genomic variation and that much of the genomic variation that actually affects gene expression is under negative selection. Now, as a postdoctoral researcher at the University of California, Davis, I am continuing to investigate the evolutionary forces shaping variation by studying if and how local adaptation contributes to quantitative trait variation in domesticated maize. My goal is to not only answer these questions in maize but to also develop methods that will be useful for investigating additional species and, overall, I hope that my work linking patterns of genomic variation with trait variation will contribute to a better understanding of how evolution shapes the world around us.

See Emily Josephs’ presentation abstract.

Emily C. Moore

North Carolina State University

One of my overarching research questions is ‘how do changes to the genome allow for the varied patterns of behavior we see reflected across the animal kingdom?’ I was inspired to start exploring this idea during my undergraduate study of biology and philosophy of mind, and I hope to continue to ask questions like these through the rest of an academic career. I have always been curious about how biological systems work, though it wasn’t until my early twenties that I recognized that a career in scientific research would be more engaging than a career in medicine—where I could contribute to the field of knowledge rather than merely absorb it. One of the focuses of my doctoral work has been to understand the genetic basis of behavioral differences between ecologically-varied cichlid fish species. I have been fortunate to be able to identify an interesting phenotype (an exploratory behavior), explore the genetic architecture of the behavior, and ultimately identify and evaluate a specific genetic variant within the time span of a PhD. The beauty of asking these questions in an ecologically and evolutionarily interesting vertebrate model organism is that our findings are relevant to the fields of evolutionary ecology and vertebrate neurobiology. The more we understand about how natural variation in the vertebrate genome shapes the development and function of the brain, the better insight we can have into how behavioral patterns evolve, and how disruption to neurogenetic pathways can lead to brain and behavioral dysfunction.

Katherine Xue

University of Washington

I never liked biology before I started learning about evolution. As a kid, I was fascinated by the order and rigor of math, but biology seemed like a chaotic mess. It wasn’t until high school that a teacher suggested I read books by Stephen Jay Gould and Richard Dawkins. Before long, I was hooked. I wanted to understand how evolutionary principles could unify and explain what Darwin called life’s “endless forms most beautiful.”

I started combining my quantitative leanings with my new love of biology. As an undergraduate, I bred tetraploid plants to understand how meiosis adapts to the tangled complications of having extra chromosomes. After graduating, I worked for a year as a science writer, inspired by the writers who first brought me to evolutionary biology.

As a graduate student, I study the lightning-fast evolution of influenza. Flu viruses change incredibly rapidly, requiring constant monitoring and vaccine updates. Recent advances in genome sequencing make it possible to track this evolution at high resolution. My work has shown that flu viruses can rapidly and repeatedly evolve to cooperate with one another in laboratory settings. I’ve also used new sequencing technologies to zoom in on how flu evolves in individual people while they’re sick. Surprisingly, I found that flu viruses can evolve in infected people over time in ways that mirror global evolution, which helps us understand better how flu evolution starts. I find it exciting and inspiring that evolutionary principles can shed light on important problems affecting human health.

Go to Katherine Xue’s presentation abstract.

Abstracts