A major challenge in biology is explaining how morphology evolves. While it’s clear that changes in gene regulation are ultimately responsible for the development and evolution of complex characters, we are only just beginning to understand the molecular mechanisms of gene regulatory evolution. The goal of our research program is to develop a complete mechanistic and historical explanation for how morphological characters evolve, focusing on the mechanisms of gene regulatory evolution. To answer these questions we integrate functional genomics and experimental methods to deduce the molecular mechanisms of developmental evolution.
Our paper, Regulatory evolution through divergence of a phosphoswitch in the transcription factor CEBPB, was published in Nature. The research, done in collaboration with Günter Wagner (Yale University), traces how the transcription factor CCAAT/enhancer binding protein-β (CEBPB, also known as C/EBP-β) evolved to be activated by the kinase GSK-3β. By functionally analyzing resurrected ancestral proteins coupled with next generation proteomics we showed that just three amino-acid substitutions changed how CEBPB interprets phosphorylation– from inhibition to activation.
Our paper, Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals, was published in Nature Genetics. The research, done in collaboration with Günter Wagner (Yale University), used a combination of comparative transcriptomics, genomics, and a suite of experimental methods to show that a common class of transposable element (called MER20) invaded the genome of early placental mammals (Eutherians) and were coopted into gene regulatory elements that drive the uterine expression of hundreds of genes across the genome.