The objective of this research is to assess the contribution of DMA-mediated transposons in shaping the genomes of humans and other primates. The movement and accumulation of DMA transposons have been shown to provoke a wide spectrum of mutations, including gross chromosomal rearrangements, in diverse eukaryotic species and has been regarded as a potential source of instability in the human genome. However, the evolutionary history and amplification dynamics of DMA transposons have not been thoroughly investigated for any mammalian species and it is unknown whether any sources of active transposase resides in the human genome. The first goal of this project is to obtain an in-depth view of the history and distribution of DMA transposon populations residing in the human genome and evaluate their impact in primate genome evolution. As a first step toward this goal, we have determined that at least ~20% of the ~340,000 DMA transposons currently residing in our genome have inserted during the primate radiation. We will perform a multi-species genome- wide analysis of the chromosomal distribution and molecular evolution of primate-specific DMA transposons using computational tools and assess experimentally their contribution to genetic diversity in primates.
The second aim of this research is to assess the enzymatic activities of two transposases, MAR and PGBD3, which are potentially expressed in several human tissues and were identified as being among the most recently active in the human genome. We will combine comparative and evolutionary sequence analyses to in vitro and in vivo assays to test whether these proteins (or other candidate identified in the course of this research) have retained their catalytic activities.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM077582-05
Application #
8018679
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Janes, Daniel E
Project Start
2007-02-01
Project End
2012-07-31
Budget Start
2011-02-01
Budget End
2012-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$154,121
Indirect Cost
Name
University of Texas Arlington
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
064234610
City
Arlington
State
TX
Country
United States
Zip Code
76019
Kapusta, Aurélie; Suh, Alexander; Feschotte, Cédric (2017) Dynamics of genome size evolution in birds and mammals. Proc Natl Acad Sci U S A 114:E1460-E1469
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Rius, Nuria; Guillén, Yolanda; Delprat, Alejandra et al. (2016) Exploration of the Drosophila buzzatii transposable element content suggests underestimation of repeats in Drosophila genomes. BMC Genomics 17:344
Hamilton, Eileen P; Kapusta, Aurélie; Huvos, Piroska E et al. (2016) Structure of the germline genome of Tetrahymena thermophila and relationship to the massively rearranged somatic genome. Elife 5:
Malfavon-Borja, Ray; Feschotte, Cédric (2015) Fighting fire with fire: endogenous retrovirus envelopes as restriction factors. J Virol 89:4047-50
Lynch, Vincent J; Nnamani, Mauris C; Kapusta, Aurélie et al. (2015) Ancient transposable elements transformed the uterine regulatory landscape and transcriptome during the evolution of mammalian pregnancy. Cell Rep 10:551-61
Hoen, Douglas R; Hickey, Glenn; Bourque, Guillaume et al. (2015) A call for benchmarking transposable element annotation methods. Mob DNA 6:13

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