Wednesday, August 22 2018
11:30 - 12:30

Alladi Ramakrishnan Hall

The evolution of a transposase: why do some genes jump?

Sharmistha Majumdar

IIT Gandhinagar

Mobile genetic elements or transposons, which have been found in both prokaryotes and eukaryotes, constitute large portions of most eukaryotic genomes and have profound effects on gene expression and genome evolution. The human genome contains ~ 50 genes that were derived from transposable elements, many of which appear to be immobile (termed as “domesticated”) are now integral components of cellular gene expression programs.

Our research focuses on the newly discovered vertebrate homologs (THAP9) of the Drosophila P element transposase (TNP). The TNP protein is involved in the cleavage and subsequent integration of the P-element DNA transposon. P-elements are a family of DNA-based transposons in Drosophila melanogaster that move about the fruit fly genome, cause hybrid dysgenesis and have been used extensively as tools for Drosophila genetics and genomics. We have made the surprising discovery that human THAP9 is an active DNA transposase that, although “domesticated”, still retains the catalytic activity to mobilize transposons. This is the first report, beyond the V(D)J recombination system, of an active DNA transposase in the human genome.

The exact cellular function and physiological role of THAP9 is, however, still unknown although THAP proteins have been broadly implicated in various cellular processes like cell proliferation, apoptosis, pluripotency and transcription as well as human disease. Interestingly, THAP9 shares significant amino acid sequence homology with the amino-terminal THAP domain (involved in zinc-dependent DNA-binding), leucine-zipper coiled-coil dimerization domain, GTP-binding domain and catalytic domain of the Drosophila TNP.

Our current investigations include genomic, proteomic and biochemical analysis of Drosophila P-element transposon-related genes in vertebrate genomes. Our studies raise exciting questions about the evolution of TNP’s ability to transpose DNA in the fruitfly embryo, and the possibility of loss or modification of this transposition function in THAP proteins in higher vertebrates by the gain or loss of additional domains and regulatory elements.

*We also actively collaborate with Computer Science colleagues to carry out integrated computational analysis of large scale NGS data for unbiased pattern mining and to accurately define genome-wide binding profiles of proteins.

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