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 undertaken, compared 240 mammalian species spanning over 100 million years of evolutionary history. This work revealed that at least 11% of the human genome is evolutionarily constrained, and that these constrained bases are more enriched for variants explaining common disease heritability than any other functional annotation. Yet nearly half of the most highly constrained bases remain unannotated in existing 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 cellular 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 mammals 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 genomic mechanisms that enable these exceptional traits may reveal new strategies for improving human health.

Speaker Bio

Elinor Karlsson, PhD, is an associate professor in Genomics and Computational Biology at the UMass Chan Medical School, and director of Vertebrate Genomics at the Broad Institute of MIT and Harvard. Her research combines large-scale comparative genomics, new technology and community science to investigate diseases and discover the origins of exceptional mammalian traits.  Dr. Karlsson’s research includes the Zoonomia project, an international effort to compare the genomes of over 240 mammals (from the African Yellow-spotted Rock Hyrax to the Woodland Dormouse) and identify segments of DNA that are important for survival and health. Dr. Karlsson also has a special interest in pet genetics. Her international Darwin’s Ark project invites all dog and cat owners to enroll their dogs in an open data research project exploring the genetic basis of behavior, as well as diseases such as cancer.

Elinor received her B.A. in biochemistry/cell biology and her B.F.A. (Bachelor of Fine Arts) from Rice University, and earned her Ph.D. in bioinformatics from Boston University. She was a postdoctoral fellow at Harvard University before starting her research group at UMass Chan in 2014, where she is Dr. Eileen L. Berman and Stanley I. Berman Foundation Chair in Biomedical Research.