The Role of Retrotransposons in Gene Family Expansions in the Human and Mouse Genomes

WOS: 000384307900001PubMed: 27503295Retrotransposons comprise a large portion of mammalian genomes. They contribute to structural changes and more importantly to gene regulation. The expansion and diversification of gene families have been implicated as sources of evolutionary novelties. Given the roles retrotransposons play in genomes, their contribution to the evolution of gene families warrants further exploration. In this study, we found a significant association between two major retrotransposon classes, LINEs and LTRs, and lineage-specific gene family expansions in both the human and mouse genomes. The distribution and diversity differ between LINEs and LTRs, suggesting that each has a distinct involvement in gene family expansion. LTRs are associated with open chromatin sites surrounding the gene families, supporting their involvement in gene regulation, whereas LINEs may play a structural role promoting gene duplication. Our findings also suggest that gene family expansions, especially in the mouse genome, undergo two phases. The first phase is characterized by elevated deposition of LTRs and their utilization in reshaping gene regulatory networks. The second phase is characterized by rapid gene family expansion due to continuous accumulation of LINEs and it appears that, in some instances at least, this could become a runaway process. We provide an example in which this has happened and we present a simulation supporting the possibility of the runaway process. Altogether we provide evidence of the contribution of retrotransposons to the expansion and evolution of gene families. Our findings emphasize the putative importance of these elements in diversification and adaptation in the human and mouse lineages.NextGenProject [CZ.1.07/2.3.00/20.0303]; Charles University in Prague Institutional Research Support [SVV 260 208/2015]; National Cancer Institute at the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [U54 CA143924, P30 CA23074]; American Cancer SocietyAmerican Cancer Society [74-001-34-IRG]; Czech National Grid Infrastructure MetaCentrum running under the program "Projects of Large Research, Development, and Innovations Infrastructures" [CESNET LM2015042]This work was supported by the NextGenProject [grant number CZ.1.07/2.3.00/20.0303 to V.J and A.Y.], Charles University in Prague Institutional Research Support [grant number SVV 260 208/2015 to V.J.]. The National Cancer Institute at the National Institutes of Health [grant numbers U54 CA143924 and P30 CA23074 to C.M.L.] and the American Cancer Society Institutional Research Grant [grant number 74-001-34-IRG to C.M.L.]. High-throughput computational capacity was provided by the Czech National Grid Infrastructure MetaCentrum running under the program "Projects of Large Research, Development, and Innovations Infrastructures" [grant number CESNET LM2015042]. The funding bodies played no role in determining study design, data collection, analysis, and interpretation, or in writing the article. The authors thank Stephen Proulx for helpful discussion on modelling of the gene family size expansion, Pavel Mundinger in whose lab VJ was based, and Libor Morkovsky for technical support with the UNIX server based at Charles University in Prague