The evolution of genome regulatory landscapes

Gene expression is regulated by non-coding genomic regions including enhancers or regulatory RNAs. It is now well established that genetic variation affecting regulatory sequence can contribute to both disease and adaptation, and we now have the unprecedented ability to biochemically profile genomic regulatory activity using high-throughput sequencing technologies. Yet, we know very little about how the regulatory genome evolves. What are the forces that establish and shape gene regulatory landscapes, and drive their evolutionary divergence across species? My research program integrates genomic analyses and experimental studies to study the molecular basis of regulatory evolution. My studies focus on the emerging and potentially extensive role of genomic parasites, known as transposable elements, in the evolution of gene regulatory networks.

 

Transposable elements in immune gene regulatory networks

Upon discovering transposable elements in maize, Barbara McClintock intuitively hypothesized that they could serve as “controlling elements” during maize development. TEs are ubiquitous selfish genetic parasites that propagate within host chromosomes. For example, the over 50% of the human genome is composed of various types of TE-derived sequences, most of which are ancient and no longer actively replicating. Having already evolved the ability to hijack the host transcriptional machinery, TEs are a potent source of “pre-built” regulatory sequences that can alter host gene expression. My research seeks to understand how TE-derived regulatory variation impacts organismal biology and evolution, at both genome-wide and functional levels.

Chuong EB, Elde NC*, Feschotte C*. Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science (2016) vol. 351: 1083-1087

Rapid evolution of the mammalian placenta

The mammalian placenta is a recent adaptation that allowed for direct maternal-fetal interactions during pregnancy. Despite its pivotal role in supporting early embryonic development in all mammals, the placenta exhibits surprising diversity in its development, morphology, and physiology. Intriguingly, placental cells exhibit much high activity from ERV elements. Using ChIP-Seq to compare the placental enhancer landscapes between mouse and rat, we identified hundreds of active mouse-specific enhancers derived from a mouse-specific ERV named RLTR13. These findings implicate ERVs as potential drivers of rapid evolution of cis-regulatory landscapes in the developing placenta.

Chuong EB, Rumi MA, Soares MJ, Baker JC. Endogenous retroviruses function as species-specific enhancer elements in the placenta. Nature Genetics (2013) 45: 325-329. PMCID: PMC3789077

Chuong EB. Retroviruses facilitate the rapid evolution of the mammalian placenta. Bioessays (2013) 35:10 853-861 

Chuong EB, Tong W, Hoekstra HE. Maternal-fetal conflict: Rapidly evolving proteins in the rodent placenta. Molecular Biology and Evolution (2010) vol. 27 (6):1221-1225.