An important area of research involves learning how gene expression influences health and disease risks. The parts of the genome that regulate gene expression are cis-regulatory elements. Gregg and colleagues took an unusual approach to discover these cis-regulatory elements by analyzing the genomes of species that evolved disease resistance “superpowers”. For example, elephants have large bodies with many cells and have evolved unique mechanisms to prevent cancer. By comparing the elephant genome to smaller, less cancer-resistant species, they uncovered putative master cis-regulatory elements in the genome that shape mammalian cancer resistance.
In a separate study, they studied hibernating mammals that have evolved unique controls over metabolism, obesity, and aging. By comparing their genomes to non-hibernating species, they found cis-regulatory elements that are putative master regulators of mammalian obesity, feeding, metabolism, and aging. In total, the Gregg lab has analyzed the genomes of over ten species with different biomedical superpowers, creating an atlas of cis-regulatory elements linked to clinically relevant phenotypes.
Accelerated evolution in distinctive species reveals candidate elements for clinically relevant traits, including mutation and cancer resistance. Ferris E, Abegglen LM, Schiffman JD, Gregg C. Cell Rep. 2018 Mar;22(10):2742.
Parallel accelerated evolution in distant hibernators reveals candidate cis elements and genetic circuits regulating mammalian obesity. Ferris E, Gregg C. Cell Rep. 2019 Nov;29(9):2608.