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.
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