Speaker: Elinor Karlsson (University of Massachusetts Medical School / Broad Institute)

Title:  Exploring 100 million years of mammalian evolution for the origins
of exceptional traits

Abstract: The Zoonomia Project, one of the largest comparative genomics initiatives ever un-
dertaken, compared 240 mammalian species spanning over 100 million years of evo-
lutionary history. This work revealed that at least 11% of the human genome is evo-
lutionarily constrained, and that these constrained bases are more enriched for vari-
ants explaining common disease heritability than any other functional annotation.
Yet nearly half of the most highly constrained bases remain unannotated in exist-
ing datasets, underscoring how much of the genome’s regulatory landscape remains
unexplored. Building on this foundation, we are integrating the “common garden”
framework from classical ecology with modern genomics to assay and compare cel-
lular responses across diverse mammals. This effort includes RNA-seq and ATAC-
seq profiling across 12 species and seven experimental states varying in temperature,
oxygen, and glucose levels. We can identify molecular responses shared across mam-
mals and those unique to species with remarkable physiological adaptations—such
as camels that thrive in extreme heat, seals that dive deeply without suffering oxygen
damage, and bats that tolerate extreme blood sugar fluctuations. Uncovering the ge-
nomic mechanisms that enable these exceptional traits may reveal new strategies for
improving human health.

In person or on Zoom at https://mit.zoom.us/j/93513735220