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Frequent Non-Allelic Gene Conversion On The Human Lineage And Its Effect On The Divergence Of Gene Duplicates

By Arbel Harpak, Xun Lan, Ziyue Gao, Jonathan K. Pritchard

Posted 08 May 2017
bioRxiv DOI: 10.1101/135152 (published DOI: 10.1073/pnas.1708151114)

Gene conversion is the copying of genetic sequence from a "donor" region to an "acceptor". In non-allelic gene conversion (NAGC), the donor and the acceptor are at distinct genetic loci. Despite the role NAGC plays in various genetic diseases and the concerted evolution of gene families, the parameters that govern NAGC are not well-characterized. Here, we survey duplicate gene families and identify converted tracts in 46% of them. These conversions reflect a large GC-bias of NAGC. We develop a sequence evolution model that leverages substantially more information in duplicate sequences than used by previous methods and use it to estimate the parameters that govern NAGC in humans: a mean converted tract length of 250bp and a probability of 2.5×10-7 per generation for a nucleotide to be converted (an order of magnitude higher than the point mutation rate). Despite this high baseline rate, we show that NAGC slows down as duplicate sequences diverge -- until an eventual "escape" of the sequences from its influence. As a result, NAGC has a small average effect on the sequence divergence of duplicates. This work improves our understanding of the NAGC mechanism and the role that it plays in the evolution of gene duplicates.

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