Cedric Feschotte

Associate Professor of Human Genetics

Markus Babst

B.S. University of Toulouse, France

Ph.D. University of Paris VI, Pierre and Marie Curie University, France

Research

References

cedric.feschotte@genetics.utah.edu

Cedric Feschotte's Lab Page

Cedric Feschotte's PubMed Literature Search

Research

Mobile DNA: the dark matter of the genome
My research focuses on mobile DNA, a term that encompasses diverse genetic elements able to integrate and often propagate within the genome. In eukaryotes, these include transposons and endogenous viruses.

Mobile DNA is found in nearly all organisms and often account for a sizeable fraction of the genetic material. For example, transposons and their remnants make up at least 40 percent of the human genome and endogenous retroviruses account for another 8 percent. One may find it unsettling that half (or more) of our own genetic material is derived from genetic parasites and viruses!   

Mobile DNA is often referred to as the ‘dark matter of the genome’ because we still poorly understand its functional significance. Yet the short-term, mutagenic effect of mobile elements on the structure and expression of the genome has been well documented. For example, over a hundred human diseases, such as hemophilia A and several cancers, are directly linked to de novo insertion or recombination of transposable elements. But much less is known about the long-term impact of mobile elements on the biology and evolution of species and on the mechanisms through which these parasitic elements persist over eons. These are the issues we are focusing on.     

Major Questions
Research in my laboratory uses a combination of experimental and computational approaches to address three fundamental questions at a genome-wide scale: 

(1) What are the mechanisms allowing for the persistence of transposons?
We have uncovered flagrant cases of horizontal transfers where transposons have crossed species boundaries on multiple occasions to invade the genome of widely diverged animals, including mammals. But how common are these ‘jumps’ across species and how do they happen? 

(2) What is the biological significance of endogenous viruses and what do they tell us about host-virus evolution?
Endogenous viruses can be viewed as molecular fossils that have been deposited in the genome during past viral invasions. By excavating and analyzing such genomic relics we have the opportunity to explore viral evolution at a depth unreachable when studying modern viruses. This information has the power to yield critical insights and predictions relevant to pathogenic viruses circulating now as well as those threatening to trigger the next pandemics. 

(3) What is the contribution of mobile DNA to the advent of new biological functions, and in particular regulatory evolution?
Although mobile elements are sometimes dismissed as merely ‘junk DNA’, there is now compelling evidence that they have profoundly influenced the evolution of genes and genomes. Currently we are studying the origin and function of genes and non-coding regulatory sequences that have emerged from mobile elements in human and in other vertebrates. We aim to assess the extent by which mobile elements have contributed to the advent of biological innovation.

Integrative Approach
Given the ubiquitous nature of mobile DNA and the ever-growing accessibility of whole genome sequencing, we do not restrict our research to a single model species or even a group of organisms. Instead, we are studying the genomes of a broad range of eukaryotic species, with a primary emphasis on vertebrates, including humans. Our research uses an integrative approach that hinges on a foundation of bioinformatics and comparative sequence analyses typically performed at the genome-wide level.  The findings and patterns deciphered at the computer are then taken to the wet lab to test specific hypotheses in the most appropriate experimental systems, often in collaboration with other laboratories. These include functional analyses in vitro and ex vivo in mammalian cells, as well as genetic analyses in model organisms.

Selected Publications

  1. Sun C, Feschotte C, Wu Z & Mueller RL (2015) DNA transposons have colonized the genome of the giant virus Pandoravirus salinus. BMC Biology 13: 38
  2. Lynch VJ et al. (2015) Ancient transposable elements transformed the uterine regulatory landscape and transcriptome during the evolution of mammalian pregnancy. Cell Reports 10: 551-61
  3. Kapusta A & Feschotte C (2014) Volatile evolution of long noncoding RNA repertoires: mechanisms and biological implications. Trends in Genetics 30: 439-52
  4. Castoe TA et al. (2013) The Burmese python genome reveals the molecular basis for extreme adaptation in snakes. PNAS 110: 20645-20650
  5. Chuong EB & Feschotte C (2013) Transposons up the dosage. Science 342: 812-813
  6. Feschotte C & McCormick JF (2013) Evolutionary history and impact of human DNA transposons. In: Encyclopedia of Life Sciences, Wiley and Sons.
  7. Zhuo X, Rho M & Feschotte C (2013) Genome-Wide Characterization of Endogenous Retroviruses in the Bat Myotis lucifugus Reveals Recent and Diverse Infections. Journal of Virology 87: 8493-8501
  8. Kapusta A, Kronenberg Z, Lynch VJ, Zhuo X, Ramsay L, Bourque G, Yandell M & Feschotte C (2013) Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs. PLoS Genetics 9: e1003470
  9. Li X, Mitra R, Kapusta A, Mayhew D, Mitra, RD, Feschotte C & Craig NL (2013) Functional characterization of piggyBat from the bat Myotis lucifugus unveils an active DNA transposon in a mammalian genome. Proc. Natl. Acad. Sci. USA 110: 234-239
  10. Feschotte C & Gilbert C (2012) Endogenous viruses: insights into viral evolution and impact on host biology. Nature Reviews Genetics 13:283-296
  11. Gilbert C & Feschotte C (2010) Genomic fossils calibrate the long-term evolution of Hepadnaviruses. PLoS Biology 8:e1000495
  12. Schaack S, Gilbert C & Feschotte C (2010) Horizontal transfer of transposable elements and why it matters for eukaryotic evolution. Trends in Ecology and Evolution 25:537-546
  13. Gilbert C, Schaack S, Pace JK, II, Brindley PJ & Feschotte C (2010) A role for host-parasite interactions in the horizontal transfer of DNA transposons across animal phyla. Nature 464:1347-1350
  14. Pace JK, II, Gilbert C, Clark MS & Feschotte C (2008) Repeated horizontal transfer of a DNA transposon in mammals and other tetrapods. Proc. Natl. Acad. Sci. USA 105:17023-17028
  15. Feschotte C (2008) Transposable elements and the evolution of regulatory networks. Nature Reviews Genetics 9:397-407
  16. Lin R, Ding L, Casola C, Ripoll DR, Feschotte C & Wang H (2007) Transposase-derived transcription factors regulate light signaling in Arabidopsis. Science 318:1302-1305
  17. Feschotte C & Pritham EJ (2007) DNA transposons and evolution of the eukaryotic genome. Annual Review of Genetics 41:331-338

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