Genetic Basis of Human Morphological Evolution
A major focus of the lab is working to identify the genetic basis for human morphological traits, particularly defining the developmental genetic mechanisms of neocortical expansion and the reorganization of craniofacial skeletal elements in the human lineage. We use both 'Functional Genomics' and more targeted, gene-centric, approaches to identify and functionally characterize human-specific genetic changes. In addition to exploring brain and craniofacial evolution, we are also studying the evolution of pregnancy and testis-specific chromatin remodeling proteins in the human-lineage. Learn more.
Representative Publications: Comming soon.
Evolution of Mammalian Pregnancy
We are studying the developmental genetic basis for origin of pregnancy in mammals, a major evolutionary novelty. Using a combination of comparative transcriptomics, functional genomics, and in vitro/in vivoexperimental hypothesis testing we are working to determine how genes were recruited into or lost from uterine expression during the evolution of pregnancy, and elucidate their roles in implantation and the establishment of pregnancy. We are also working to determine if genes important for the evolution of pregnancy play a role in the etiology of infertility and pathologies of pregnancy such as preeclampsia and preterm birth. Learn more.
Lynch VJ et al., 2014 "Ancient Transposable Elements Transformed the Uterine Regulatory Landscape and Transcriptome during the Evolution of Mammalian Pregnancy" Cell Reports, 10: 551-561 (read)
Lynch VJ, LeClerc R, Mae G, and Wagner GP 2011 “Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals” Nature Genetics 43: 1154-1159 (read)
Woolly Mammoth Paleogenomics
Woolly mammoths and the living elephants have major phenotypic differences that have allow to live in very different environments. To identify the genetic changes that underlie the suite of adaptations in woolly mammoths to life in extreme cold, we have collaborated with several groups generating whole genome sequences of woolly mammoths and are functionally characterizing mammoth-specific nucleotide and amino acid changes. Learn more.
Lynch VJ, Bedoya-Reina OC, Ratan A, Sulak M, Drautz-Moses DI, Perry GH, Miller W, and Schuster SC. 2015 "Elephantid Genomes Reveal the Molecular Bases of Woolly Mammoth Adaptations to the Arctic." Cell Reports, 12: 217-228 (read)
Functional Molecular Evolution
Determining how the function of genes and proteins originated and diversified during evolution is essential for developing a mechanistic understanding of evolution – both to provide a historical explanation for how biological systems arose and to understand evolution as a process so that we may infer general rules of (molecular) evolutionary change. For example, is the path of mutational change in proteins constrained in such a way that evolution is predictable? Is evolution reversible or does a molecular Dollo's law constrain reversion? And, more generally, how do new functions emerge from existing ones?
We most often explore these questions in the context of regulatory control of gene expression by transcription factors, particularly Hox genes. Regardless of the specific experimental system, however, our goal in these studies is to combine evolutionary inferences with the rigorous experimental methods of molecular biology, biochemistry, and structural biology to develop a complete mechanistic and historical explanation for how complex molecular systems evolve. Learn more.
Lynch VJ, Mae G, and Wagner GP. 2011 “Regulatory evolution via adaptive divergence of a phosphoswitch in the transcription factor CEBPB” Nature 480: 383-386 (read)
Lynch VJ, Tanzer A, Wang Y, Leung FC, Gellersen B, Emera D, and Wagner GP. 2008 “Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals” Proceedings of the National Academy of Sciences USA 105(39): 14928-14933 (read)