Dr. Stéphane Boissinot
Ph.D., Université Montpellier II
Office: NSB D322 Tel: 718 997 3437;
Laboratory: NSB D343 Tel: 718 997 3233
My laboratory is conducting research on the evolution of mammalian transposable elements (mostly in rodents and primates) and on the impact the activity of transposable elements has had on the structure and function of mammalian genomes.
L1 (LINE-1) elements constitute the major family of transposable elements in mammalian genomes. They are called retrotransposons because they replicate by copying their RNA transcript into DNA, which inserts into the host genome. L1 elements have been replicating and evolving in mammalian genomes since before the mammalian radiation, ~100 million years ago. The human genome contains at least 500,000 L1 elements that account for ~17% of its mass. In addition, the replicative machinery encoded by L1 can act on other transcripts and is believed to be responsible for the amplification of the SINEs elements (such as the Alu family in primates) that account for another ~13% of the genome. Altogether, L1 activity is responsible for more than 35% of the total DNA present in our genome.
New L1 inserts can be a source of polymorphisms and genetic defects. They can also mediate chromosomal rearrangements due to ectopic (non-allelic) recombination and alter the regulatory properties of genes. These effects are potentially deleterious and the control of L1 replication might be important for maintaining host fitness. However, despite the negative effects L1 can have on its host genome, L1 has remained active in the vast majority of the mammalian species studied so far. Resolving this paradox is one of the questions we are addressing in my laboratory. Our laboratory is using a combination of bioinformatics and standard molecular biology techniques to investigate mammalian L1. Using the tools of bioinformatics, we identify in complete genome sequences the evolutionary period during which L1 activity has been the most intense. Then we determine the evolutionary history of L1 elements to identify the features of L1 elements and the characteristics of their genomic environment that could be responsible for their replicative success. The features that seem important are further investigated experimentally by comparing them in species that differ in the intensity of L1 amplification. For example, earlier studies revealed that the first open-reading frame of L1 might play a role in the interaction of L1 with its host. To confirm this hypothesis, we are currently analyzing this region of L1 in primate and rodents species that differ in their rate of L1 activity.
Another direction our research is taking is the use of L1 elements for addressing evolutionary questions. Because L1 inserts are robust genetic characters, they can be used as markers in phylogeny and population genetics. We are currently investigating their use in New-World monkey and in Old World murine rodents (mice and rats) phylogeny.
M. Song, R.M. Haralick, and S. Boissinot (2010). Efficient and exact maximum likelihood quantization of genomic features using dynamic programming. Int. J. Data mining and Bioinformatics 4(2): 123-141.
P. Novick, J. Smith, D. Ray and S. Boissinot (2010). Independent and parallel lateral transfer of DNA transposons in tetrapod genomes. Gene 449: 85-94.
P. Novick, H. Basta, M. Floumanhaft, M. McClure, and S. Boissinot (2009). The evolutionary dynamics of non-LTR retrotransposons in the lizard Anolis carolinensis shows more similarity to fish than mammals. Mol. Biol. Evol.26: 1811-1822.
W. Ferguson, S. Dvora, J. Gallo, A. Orth and S. Boissinot (2008). Long term balancing selection at the West Nile virus resistance gene, Oas1b, maintains trans-specific polymorphism in the house mouse. Mol. Biol. Evol. 25(8): 1609-1618.
M. Song and S. Boissinot (2007). Selection against LINE-1 retrotransposons results principally from their ability to mediate ectopic recombination. Gene 390 (1-2): 206-213.
S. Boissinot, J. Davis, A. Entezam, D. Petrov and A.V. Furano (2006). Fitness cost of LINE-1 (L1) activity in humans. Proc. Natl. Acad. Sci. USA 103 (25): 9590-9594.
H. Khan, A. Smit and S. Boissinot (2006). The evolution of human LINE-1 retrotransposons since the origin of primates. Genome Research 16(1): 78-87.
S. Boissinot, Entezam A, Young L, Munson P, and Furano AV (2004). The insertional history of an active family of LINE-1 retrotransposons in humans. Genome Research 14: 1221-1231
A.V. Furano, D. Duvernell and S. Boissinot (2004). L1 (LINE-1) retrotransposon diversity differs dramatically between mammals and fish. Trends in Genetics 20(1): 9-14.
S. Boissinot and A.V. Furano (2001). Adaptive evolution in LINE-1 retrotransposons. Mol. Biol. Evol. 18(12): 2186-2194.
S. Boissinot, A. Entezam and A.V. Furano (2001). Selection against deleterious LINE-1-containing loci in the human lineage. Mol. Biol. Evol. 18: 926-935
S. Boissinot, P. Chevret and A.V. Furano (2000). L1 (LINE-1) retrotransposon evolution and amplification in recent human history. Mol. Biol. Evol. 17(6): 915-928.
S. Boissinot, Y. Tan, S.-K. Shyue, H. Schneider, I. Sampaio, K. Neiswanger, D. Hewett-Emmett and W.-H. Li (1998). Origins and antiquity of X-linked triallelic color vision systems in New World monkeys. Proc. Natl. Acad. Sci. USA 95: 13749-13754.
D. Casane, S. Boissinot, B.H.-J. Chang, L. Shimmin and W.-H. Li (1997). Mutation pattern variation among regions of the primate genome. J. Mol. Evol. 45: 216-226.
S. Boissinot and P. Boursot (1997). Discordant phylogeographic patterns between the Y chromosome and mitochondrial DNA in the house mouse: selection on the Y chromosome?. Genetics 46: 1019-1034