© MATT KALINOWSKIBrandon Gaut loved genetics, but he did not like experimenting with mice. An undergraduate at the University of California, Berkeley, in the early 1980s, Gaut worked in a molecular immunology lab studying mouse histocompatibility complexes, which required sacrificing and grinding up his subjects to isolate their DNA. “I just wasn’t into that,” says Gaut. “So I thought, ‘What can I study where I don’t have to feel bad?’ And I decided I wouldn’t feel bad if I cut up a plant.”
That decision catapulted Gaut into the vegetable kingdom and onto his ultimate career path. In 1988, he joined the lab of plant geneticist Michael Clegg at the University of California, Riverside, just as the DNA-amplifying technology of PCR was opening up the field of genetics to large, systematic studies. “It was an exciting time to be in the lab, because we were sequencing genes from all kinds of different plant species,” says Gaut. As a graduate student with Clegg, Gaut compiled DNA sequence data from plant chloroplasts to test an evolutionary hypothesis: the possibility that mutations occur in a species’ genome at a regular pace through time. Gaut showed that there is indeed a molecular clock in plants, and its pace is linked to their generation time. Long-lived species like palms, he found, accumulate mutations more slowly than fast-growing plants like grasses.
“I’ve always loved the approach of experimental evolution, because it’s akin to domestication, where you can assume things about what’s happening.”
Gaut would continue to pursue ideas about the molecular clock for the next 25 years, and his curiosity about plant evolution has yet to wane. He has since explored the amount of genetic variation in plants, how a bottleneck shapes a species’ evolution, how transposable elements affect evolution, and, most recently, whether evolution is replicable. Given a single environmental pressure, does a species evolve the same way every time?
“I love working on new questions,” says Gaut. “Once something has been answered, then it gets boring for me.”
Here Gaut opines on why evolutionists shouldn’t disparage artificial selection, what it’s like to work side by side with a spouse, and the best ways to convince students that biology is “badass.”
Gaut and The Genome
Brandon Gaut, MD? “I thought I wanted to be a pediatrician—I loved little kids. I was at UC Berkeley and was frankly afraid of chemistry and physics and all that stuff you have to do to be premed. I finally convinced myself that I would really regret it if I didn’t take some of those classes and at least try. So I took some and really ended up liking genetics. Then I got started in a genetics lab and loved doing the research. By the time I had to take the MCAT [Medical College Admission Test], I realized that everything on the test was boring to me and all the interesting parts of biology were not going to be in med school.”
Beach bum. “I took 2 years off as gap years. To be honest, it was motivated by the chance to live at the beach. I took a job with a pharmaceutical company in Irvine, California, where I worked with radioactive nucleotides and making the P32 label that people would use for sequencing. It was a heinous job, but I knew it was a short-term thing. The great news was, I did get to live at the beach, and I met my wife, so it all turned out well.”
Tick tock. In 1988, Gaut gave up the beach to work with Clegg at UC Riverside. “I just loved it. It was fortuitous. He’s one of the greatest human beings I’ve ever met.” It was at Riverside with Clegg that Gaut made the molecular clock discovery, demonstrating that palms, a family with an 8- to 40-year generation time, molecularly evolve about eight times more slowly than plants that reproduce annually—work published in 1992 in the Journal of Molecular Evolution. But why plants with longer generation times have slower molecular clocks remains a mystery in evolution, says Gaut. “It makes intuitive sense, but we still really don’t know why that is. It’s one of those outstanding, interesting questions that no one has really answered in the past 25 years.”
A-maize-ing variation. After that paper, Gaut turned his sights to figuring out how much genetic variability exists among individual plants, a novel question at the time, by studying nuclear genes in domesticated maize. “We found more [variation] than we expected. It turns out maize is a very variable species,” says Gaut. “Then I wanted to understand the evolutionary processes that affect this genetic variation. That got me started in population genetics in agricultural species, and I spent the next 20 years of my career working in corn. It struck me as a really exciting system, though lots of people said to me, ‘Why do you want to study population genetics in domesticated plants? It’s so artificial, not natural.’ But in the end, we ended up doing a lot of things before anybody else, because it was a controlled system that we could make hypotheses about.”
Double down. Gaut began one of his first corn projects as an assistant professor at Rutgers University in Newark, New Jersey. “With John Doebley, a longtime collaborator and fantastic scientist, I did the first study using gene-sequence differences within a genome to understand the polyploidy history of a genome.” All plants have polyploidy—a complete genome duplication—somewhere in their history, says Gaut. In 1997, he and Doebley published the first study in plants to detail the timing of duplication events in the maize genome, showing that maize underwent a whole-genome doubling event roughly 11 million years ago, via hybridization between two ancestors that had diverged some 9 million years earlier.
Message in a bottle(neck). Gaut also realized that corn was a perfect model to study bottlenecks—a fundamental concept in evolution. “We know where corn came from, know something about its wild relatives, and know the timing of the process of domestication. We know the relatives of maize had a lot of genetic variability, and when it was domesticated we took just a subset of that variability, called a bottleneck. I thought we might be able to model what that bottleneck looked like: how long was that bottleneck, how wide? We were the first people ever to use DNA sequence data for population history in that manner. It’s used all the time now for humans, with out-of-Africa bottleneck models, but it was first done in maize.” That bottleneck work, which began with a 1998 PNAS paper, culminated in a 2005 Science paper in which Gaut and colleagues describe the estimated 1,200 genes in the maize genome that are affected by artificial selection. “In the end, it was a lot more genes affected by domestication than we anticipated. We also showed those genes were in genomic regions that differentiate maize and teosinte, its wild grass ancestor.”
Gaut Going Strong
Evolution on the move. In 2009, Gaut began to study the evolution of transposable elements, DNA sequences that move around the genome. “Plant genomes are mostly made up of transposable elements, so if we don’t understand what’s going on with them, we don’t understand plant genomes. A wonderful graduate student of mine named Jesse Hollister had the insight that we’d better start looking at epigenetic variation, because transposable elements are modified by methylation and histone variants.” The first paper was published in Genome Research and then a follow-up in PNAS. They found that differential DNA methylation silencing of transposable elements in two species of Arabidopsis contributed to genetic differences between the species. “That really got me interested in epigenetic modification and what that means for evolution and the evolutionary process. That’s a very active part of my lab now.”
It’s getting hot in here. “I’ve always loved the approach of experimental evolution, because it’s akin to domestication, where you can assume things about what’s happening. In experimental evolution, you’re controlling evolution to answer whatever question you’re interested in. My colleagues Tony Long and Al Bennett had worked on E. coli experimental evolution in the past and were trying to get a grant funded, which kept getting close but not all the way. I didn’t want them to give up because it was such a beautiful project, so I helped them rewrite the grant one more time, and we got it. The first thing we wanted to know was how replicable is evolution: We know E. coli can evolve in a lab, but is it always evolving in the same way, with the same genetic changes?” The team grew 115 populations of E. coli at high temperatures (42.2 °C) for a year—about 2,000 generations—then sequenced an individual from each population. “We found that across all these 115 populations, there were a couple common pathways used [to adapt to high temperature], but within those pathways, there were an almost unlimited number of mutations that could occur. That means there is this weird constraint—a couple of common pathways that seem to be the best way to evolve—but within those common pathways, there is a ton of flexibility.” The team is now studying gene expression among the mutated E. coli populations to identify new phenotypes resulting from those genetic mutations.
“Oh God, I love teaching. Do I ever. To me, if they don’t become biologists but they finish the class and think, ‘Man, that stuff was badass,’ then it’s a success.”
Ag applications. “One reason I like working in maize and other cultivated crops is that there is always hope there is some practical value in what I do. It turns out there is. We can identify genes under selection, genes modified through the process of artificial selection over the last 10,000 years, in corn or any crop. This is an approach to find genes of agronomic importance. If you look just at current genes through QTL [quantitative trait locus] sequencing, you tend to find only genes that have retained some genetic variability.” By looking into the past, however, it’s possible to identify genes that contribute to agronomically important traits but may have been selected over time and lost all their variability. “It’s a complementary way to look for gene variants,” he says.
Juggling chairs. From 2006 to 2012, Gaut served as chair of the Department of Ecology and Evolutionary Biology at UC Irvine. “It was hard. It was a tough time in the state budget, with tough decisions to make. And if you like to do things well, it’s hard to be good at administration—keeping your faculty happy—while trying to keep your own research going. But I enjoyed it, actually. I liked administration a lot. But I found it really hard to keep all the balls in the air.”
Professor of the Year. “Oh God, I love teaching. Do I ever. I used to teach freshman biology often, classes of 300–400 people, the first class any biology major would take. For me, the real goal was to get them excited. I didn’t care so much if they knew a litany of facts at the end of the class, but I wanted them to come away with one or two examples of why biology is neat. For example, I’d take them through a slide show of going down in a deep-sea submarine to see those giant tube worms. You can just tell they thought that was so amazing. To me, if they don’t become biologists but they finish the class and think, ‘Man, that stuff was badass,’ then it’s a success.” And Gaut’s approach appears to be working; in 2002 he was elected Outstanding Professor by the senior class, and in 2008 he was elected Professor of the Year at UC Irvine.
Mea culpa. “I’m kind of a horrible scientist. I didn’t grow up as a hobby scientist, I don’t read popular-science magazines, I don’t love plants or maize. I get into one question I really like and answer it. I like the questions.”
California clan. “I’m utterly blessed to be near family. My sister lives a mile and a half away, and her kids went to school with my kids. I see my parents every weekend; we have them for dinner almost every Sunday. You can’t beat it.”
Cycling, biking, and hiking. “I like to do anything having to do with sports. I have two boys, 21 and 23. One plays water polo in college, and I played that sport as a kid, so I spent lots of time going to his games. And my older son is a runner, so every year I went to Yosemite with his team and I’d run with the kids and get to know them. I dabble in surfing and used to ride bikes a lot—anything outdoors.”
Choir boy. “I’m trying to sing. It’s a very new thing. I have no kids at home anymore, so I decided I needed to get involved in the community and went down to the local church and joined the choir. I have no experience. I’m on sabbatical in Boston right now and I’m sure they’re glad the flat tenor is missing.”
Who’s the boss? “My wife worked as a technician at UC Riverside, and then we had our children during my first year of grad school, so she worked part-time on weekends and nights and I worked during the day, and we never saw each other. Then, when I got my first faculty job, I needed a technician, and there she was with great experience, and they let me hire her! She’s worked in my lab ever since. She’s incredibly good. Though sometimes she wants to talk about work at night, and I’m not happy about that.”
• As a graduate student, demonstrated that plants have a molecular clock tuned to a species
• Was the first to infer a domestication bottleneck using DNA sequence data and extended bottleneck
models to search for genes selected during maize domestication.
• With John Doebley, published the first study to explore and date the historical duplication
of a plant genome.
• With Jesse Hollister, showed that epigenetics plays an important role in the evolution
of transposable elements in plants.
• In 2012, demonstrated with colleagues that E. coli adapts to a hot environment via two survival
pathways and a wide variety of mutations.