John M. Prather Lecture Series

Dr. Molly F. Przeworski, Alan H. Kempner Professor of Biological Sciences and Systems Biology, Columbia University, to give 2024 Prather Lectures,

May 1, 2 & 3, 2024

 

Molly Przeworski_Prather 2024Dr. Molly F. Przeworski is interested in modeling how genetic and evolutionary mechanisms give rise to and maintain heritable variation, and in inferring properties of underlying mechanisms from patterns of genetic variation. Work in her group has revealed the fine-scale recombination landscape to be rapidly evolving in primates and elucidated the causes and consequences of its evolution in vertebrates. Przeworski Lab research has also clarified how natural selection operates in human populations: notably, by demonstrating that few recent human adaptations involved new, single changes of large effect and characterized the footprints of other forms of adaptation in genetic variation data.  More recent work seeks to understand sources of variation in mutation rates within and between species.

Przeworski received a B.A. in Mathematics from Princeton University and a Ph.D. from the Committee on Evolutionary Biology at the University of Chicago, after which she pursued postdoctoral training in the Department of Statistics at the University of Oxford. She held a research position at the Max Planck Institute for Evolutionary Anthropology and, before moving to Columbia University in 2014, was a faculty member at Brown University and the University of Chicago. She is the recipient of the Rosalind Franklin award from the Gruber foundation, an early career award from the Howard Hughes Medical Institute, the 2023 Scientific Achievement Award from the American Society of Human Genetics, and was elected to the American Academy of Arts and Sciences and the National Academy of Science in 2020.

Wednesday, May 1
The best laid plans of mice, men, birds and snakes: an evolutionary perspective on recombination

Abstract: In vertebrates, meiotic recombination ensures both the proper alignment and segregation of chromosomes, and modulates the efficacy of natural selection. Despite its essential roles, many aspects of the recombination process are rapidly-evolving. Notably, across mammals, recombination hotspots are specified in at least two ways: through the binding of PRDM9, as in mice and humans, and by targeting promoter-like features, as in dogs. Dr. Przeworski's work has shown that these two strategies are employed beyond mammals, and interdigitated across vertebrate species, with many independent losses of PRDM9. In this talk, she will present our research on the mechanistic basis and evolutionary selection pressures shaping the recombination landscape in vertebrates and its consequences for genome evolution.

Thursday, May 2 (co-sponsored with The Harvard Museum of Natural History)
Reading genetic tea leaves: promises and pitfalls of genomic trait prediction

Abstract: Natural populations harbor extensive genetic diversity. In 150,000 people, for instance, over 600 million positions in the genome differ among individuals. Over the past decade, it has become routine to survey this genomic variation in large samples, and to associate variation in traits (e.g., height) to these genetic differences. Such associations can then be used to predict, albeit very noisily, a person’s traits–be it their height, cancer risk, or educational attainment–from their genome. Dr. Przeworski will outline current approaches to genomic trait prediction in humans and some of their important pitfalls, notably those arising from the difficulty of disentangling genetic and environmental effects. She will also discuss how an analogous approach can be taken to study traits that are likely to be important in the response to climate change, using coral bleaching as an illustration.

Friday, May 3
Why do human germline mutation rates depend on sex and age?

Abstract: Germline mutation is the source of all heritable differences and therefore of fundamental importance. In mammals, it has long been appreciated that mutation rates are higher in fathers, particularly older fathers. The textbook view has long been that these patterns reflect replication errors that accrue during spermatogenesis. Dr. Przeworski will present multiple lines of evidence that call this view into question. She will argue instead that current data are best explained by a much larger role of DNA damage in the genesis of germline mutations than previously appreciated, and draw implications for why mutation rates depend on sex and age and how they evolve over time.