Mobile DNA: evolution and consequences
Our research focuses on mobile DNA, a term that encompasses diverse genetic elements able to integrate and often propagate in genomes. In eukaryotes, these include transposable elements and endogenous viruses.
Mobile genetic elements are found in nearly all organisms and often account for a sizeable fraction of the genetic material. For example, transposable elements and their remnants make up at least 40 percent of the human genome, while endogenous retroviruses account for another 8 percent.
The short-term, mutagenic effect of mobile DNA 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 forms of cancer, are directly linked to the insertion or recombination of mobile elements. Much less is known about the mechanisms by which mobile elements persist over long evolutionary time and how they have influenced the biology and evolution of their host species on a long-term scale. These are the issues that we are mostly dealing with in the lab.
INTEGRATIVE APPROACH. Given the ubiquitous nature of mobile DNA and the ever-growing number of whole genome sequences, we do not restrict our research to a single model species or even a group of organisms. Instead, we are exploring the genomes of a broad range of eukaryotic species, with a primary focus on DNA transposons, and more recently endogenous viruses, in vertebrate genomes. Our research uses a highly integrative approach that hinges on a foundation of computational and evolutionary sequence analyses typically performed at the genome-wide level within a phylogenetic framework. The findings and patterns deciphered at the computer are then exploited in 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 such as yeast and Drosophila.
Current projects (not so current anymore... but we're still working on these projects!!)
(1) Evolutionary history and mining of mobile elements in eukaryotic genomes.
We use and develop bioinformatic tools to automate the mining, annotation, and analysis of transposable elements and other repeats in a wide range of eukaryotes as diverse as mosquitoes, snakes, and bats!
Representative papers: Castoe et al. 2011 GBE; Arensburger et al. 2010 Science; Pace et al. 2009 PLoS Genet; Ray et al. 2008 Genome Res; Pace & Feschotte 2007 Genome Res; Pritham & Feschotte 2007 PNAS
Tool: REPCLASS - Feschotte et al. 2009 GBE
(2) Horizontal transfer: How do transposons jump between species?
We and other labs have uncovered flagrant cases of horizontal transfers where mobile elements have crossed species boundaries on multiple occasions to invade the genome of widely diverged animals. We believe this process has been largely overlooked but is actually of major importance for the survival of selfish genetic elements and the evolution of animals. But how common are these ‘jumps’ across species and how do they happen?
Review: Schaack et al. 2010 TREE
(3) What is the contribution of mobile DNA to the advent of new biological functions?
Although mobile elements are sometimes dismissed as merely ‘junk DNA’, there is growing evidence that they have been key players in shaping and diversifying genomes over eons. Currently the lab is investigating the origin of functional DNA sequences, both coding and non-coding, derived from the relics of mobile elements in vertebrates and in Drosophila. This includes the identification and functional analysis of genes originated by domestication of transposons.
(4) Paleovirology: what is the biological significance of endogenous viruses?
Endogenous viruses are molecular fossils of past viral invasions. By excavating and analyzing these 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.
Review: Feschotte & Gilbert 2012 Nature Rev Genet
Our research has been funded continuously by the National Institutes of Health (NIH) since 2007.