A Conversation with Population Geneticist David Poznik

This interview is part of an occasional series of profiles introducing you to some of 23andMe’s scientists. Population geneticist David Poznik came to 23andMe after working in Carlos Bustamante’s lab at Stanford University.

Originally from Massachusetts, David earned an undergraduate degree in Biophysics at Brown. An avid traveler and backpacker, David has taken a couple years off to explore Asia and South America. These trips bookended his time as a Senior Research Analyst at Harvard’s Joslin Diabetes Center where, among other projects, he led the analyses for a few early GWAS studies. Upon returning from South America, he went on to earn a master’s degree in Statistics and a PhD in Biomedical Informatics at Stanford. While working in Bustamante’s lab, David became an expert on the Y chromosome. He maintains strong interests in DNA sequencing, ancient DNA, and algorithm development.

Tell us about your education:

I primarily studied math and physics in my first two years at Brown, but I grew increasingly excited about the biology classes I was taking on the side, so I started shifting focus. By the end of college, I was splitting my time between biology and physics, and my research in computational neuroscience was somewhere in between, so I ended up majoring in Biophysics. After college, I conducted the analyses for a number of genetic epidemiology studies at Harvard, but I returned to school in order to gain formal training in statistics and computer science. At Stanford, I earned an MS in Statistics and a PhD in Biomedical Informatics.

What’s your job title and role here at 23andMe?

I am a Computational Biologist and Population Geneticist at 23andMe. Within the Research Team, I work in the Ancestry group. We develop and improve methods to extract insights about customers’ ancestry from their genotypes.

What were you working on before you came to 23andMe?

Before joining 23andMe I was in graduate school, taking as many statistics and computer science classes as I could, while conducting research in population genetics. Most of my graduate research was focused on using Y-chromosome sequences to learn about human history. For example, as a component of the 1000 Genomes Project, our analysis of 1,244 Y-chromosomes revealed multiple historical bursts of extreme expansions in male numbers. Most recently, I developed a pipeline to process and analyze the targeted sequences of several hundred Y chromosomes from diverse African populations.

What are you working on now at 23andMe?

My first project at 23andMe is to develop and test a new algorithm to identify customers’ Y-chromosome haplogroups, with the goal of updating our ancestry reports.

Why are you excited about genetics?
I am most excited about genetics because of the vast amount of historical and anthropological information encoded in our genomes. Beginning with the pioneering work of Luca Cavalli-Sforza in the 1960’s, the field of genetics has made substantial contributions toward our understanding of the past.

In some cases these findings have confirmed pictures drawn previously by long-established disciplines such as archaeology and linguistics, but in many cases, and with increasing regularity, genetics has added wholly new elements. Two recent technological developments are driving much of the most recent work: high-throughput sequencing and methods to extract DNA from the remains of people and archaic humans who lived thousands, or even hundreds of thousands, of years ago. Together, these tools have led to a far greater understanding of the history of our species than was thought possible just a decade ago.

Tell us about one of your interesting findings in your previous scientific life.

When I started graduate school, I had the good fortune to have access to some of the first high-throughput sequencing of globally diverse populations. I developed methods to analyze and interpret the Y-chromosome data, and I built a tree relating the sequences. The root of this tree represents the most recent common ancestor (MRCA) of the Y chromosomes in the study, and the branches represent shared paternal ancestry of increasingly smaller subsets of the sample, terminating at the leaves, which represent individual sequences.

Thanks in large part to the seminal work of Peter Underhill, much was already known about the topological structure of this tree–the branching patterns that reflect the relationships between the various lineages. But, in contrast to prior work, the full sequence data enabled me to measure the distances between each of the subtrees, or “clades.” These distances are represented by the branch lengths of the tree, with longer branches indicating greater temporal separation. With full sequences, we can infer the time to the MRCA of any pair of Y chromosomes. The MRCA of all extant human Y chromosomes–the root of the tree relating the Y chromosomes of all living men, including carriers of the recently discovered “A00” haplogroup–lived ~275 thousand years ago.

One interesting fact people don’t usually guess about me is:

Something my peers in graduate school never would have suspected is that before returning to school, I actually had a great work-life balance. Since joining 23andMe a few months ago, most of my evenings and weekends have been back at Stanford wrapping up a few papers, but I’m quite excited to start getting out of lab again!

Did you learn anything interesting from your 23andMe results? Did you make any changes as a result of taking the test?

A close friend learned from her 23andMe results that she was heterozygous for Factor V Leiden, and she shared this genetic result with her doctor. In 2010, her doctor found it quite the novelty for a patient to walk into her office, genotypes in hand. She advised my friend that, due to her increased risk of developing venous thromboembolism, she should go off the pill, and my friend complied, reasoning that this was a relatively easy change in light of the potential risk. This event was actually my first window into the power and potential of direct-to-consumer genetics.

What’s one thing the average consumer should know about genetics?

The Y chromosome is remarkable in that it is the longest stretch of non-recombining DNA in the human genome, by orders of magnitude. Because this giant chunk of DNA is transmitted in whole from father to son through the generations, it contains sufficient information to build a detailed phylogenetic tree. At 23andMe, we can tell you where your paternal ancestry fits into this larger context.