A Career in Evolutionary Biology and Elucidating the Genetic Basis of Variation

Hopi E. Hoekstra, PhD, is the Alexander Agassiz Professor of Zoology in the Departments of Organismic and Evolutionary Biology, and Molecular and Cellular Biology at Harvard University. She is a Howard Hughes Medical Institute investigator studying the genetic determinants of behavior, as well as reproductive and morphologic variation. She primarily works with wild mice as a model and her efforts are helping better describe the genetic origins of variation in other vertebrates, including humans [1].

After graduating from the University of California Berkeley with a degree in Integrative Biology, Dr. Hoekstra completed her PhD at the University of Washington, where she was a Howard Hughes Pre-doctoral Fellow. She went on to study the genetic basis of adaptive melanism in pocket mice as an NIH Post-doctoral Fellow at the University of Arizona. Dr. Hoekstra was an Assistant Professor at the University of California, San Diego, before joining the faculty at Harvard University, where she is also the Curator of Mammals at the Museum of Comparative Zoology.

Could you please tell us a bit about your personal and professional background, and what motivated you to pursue research?

Growing up I was always really interested in history, so actually I went to college thinking I was going to major in political science. I think it was through just spending time in the natural world that I got more and more interested in biology, and I realized I was less and less interested in political science. When I was a sophomore, I switched and took the introductory biology classes and required physics and chemistry courses and so forth. But the thing that really got me started in science was during that sophomore year, I took a more advanced class in comparative physiology, and in that class we actually did experiments, summarized our own data, and we did research presentations. So I got a taste of what it would be like to be a researcher, and then I was invited into that professor’s lab to conduct research. So for me, that was the clear defining time.

How did you wind up in your current field of investigation?

When I was an undergrad I was doing research in biomechanics, and during that time I fell in love with research and the process of discovery, but I didn’t fall in love with biomechanics. Then I took a sort of winding road and ended up becoming interested in organismal level questions. But when I started as a first year graduate student it was a time when I would say that the field of molecular ecology was just starting to blossom, so this represented an opportunity to use molecular tools to address some organismal questions in an unprecedented novel way. So for me, it was being in the right place at the right time. At the University of Washington they had just hired this young, hot-shot professor, Scott Edwards, a molecular ecologist, and it was a match made in heaven. I immediately joined his lab.

What are some areas of active investigation in your lab right now?

My lab has been very interested in trying to identify genes that contribute to traits that matter for the whole organism. When we started the lab we started with an eye on morphological variation, so things like pigmentation and pigment patterns, and then we moved to more complex morphological traits. But in recent years, we have taken that same approach and now started to ask questions about the relationship between genes and behavior. Most of the lab is working on the genetic basis of behavior and trying to understand how changes in genes, act in or on neural circuits to give rise to variation in behavior.

You study a wide range of topics, including population genetics, evolution and development, and behavioral genetics, what are some challenges to research in this space? Do you see that a particular topic tends to be more challenging?

One of the challenges when we moved from morphological traits to behavioral traits is quite simple, and that is, the challenge of actually measuring behavior. You could take a ruler out and measure the length of a femur, you can quite easily quantify pigmentation, type, and concentration for example in the fur of rodents, but when you start thinking about measuring behavior it becomes much more complicated, especially when you’re thinking about measuring variation, let’s say among individuals or between species. So that’s a first challenge. But what’s exciting is that the field of behavior and neuroscience has seen an explosion of new automated approaches to quantify behavioral variation, and that’s revolutionizing the field and we are trying to capitalize on that.

How has the field evolved since you started? What are some gaps in our understanding of the genetic basis of adaptation?

In recent years we’ve seen a real embracing of using emerging model systems, or what many people call “non-model systems.” So instead of just solely focusing on worms, flies, mice, and zebrafish, there is a real appreciation for additional systems as unique ways to address questions. And for some fields they’ve been doing that for a long time, but what’s fun these days is being able to capitalize on natural variation in those systems. So for the types of things we are doing, much of our work focuses on variation and trying to understand the genetic basis of that variation. Turning to natural systems provides us with, in some sense, more variation, hence more power to dissect the genetic basis of those differences.

You have a pretty large group of graduate and undergraduate students, and postdoctoral fellows working with you on a broad range of topics. What is your approach to mentorship, and what advice would you have for individuals that may have an interest in research and perhaps starting their own lab in the future?

There are so many axes on which you can give advice. A bit challenging. I think for me what has become really important is identifying a question for which you have a passion, because being a scientist and being successful at that requires a lot of effort and dedication and persistence and motivation, so you really have to love what you do. And that’s sort of a general piece of advice. The other thing that is maybe more specific to science is, for me, some of the most exciting science happens at the interface between two separate fields. So I would advise people to think about, either addressing age old questions with new techniques and approaches, or identifying new questions that people could never have thought of, because now the world is so much more interdisciplinary.

You have obviously been very successful in the lab. What do you enjoy doing outside of the lab when you are not working?

That’s a great question, we were just joking about this the other day. What are my hobbies?

For me a lot of it is spending time with family. I have a young son who we spend a lot time with, so, Saturday morning soccer games, and local trips and so forth. More generally, I really am an avid reader, I really love to travel, and I am trying to learn how to cook.

Any last things you want our readers to know about you or research?

For me, the thing that is most fun about being a scientist is being able to follow your curiosity. And as long as you can keep your research funded, you really have this autonomy to follow the questions that you are excited about, and I find that tremendously exciting.

The other thing I find both wonderful and challenging as an academic is finding the balance between research and teaching. I love teaching, especially freshmen. So I teach a large introductory course called Genetics, Genomics, and Evolution to about 300 or 400 freshmen each spring, and it’s amazing how teaching complements research. I would say you don’t know something well until you have to teach, and boy did I get refreshed on all my basic genetics. I feel like I’m a much broader scientist because I have had to teach.

References

Howard Hughes Medical Institute Scientists [Internet].Cited11.2018.Available from:https://www.hhmi.org/scientists/hopi-e-hoekstra