Current models of genome organization and evolution are based almost entirely on correlations across species, because genome-wide manipulative experiments are not feasible. The conceptual foundation for much of the work here is to expand the foundations for testing these models by studying new taxa that have genome characteristics especially relevant to specific hypotheses. L1 elements (LINE- 1s) are retrotransposons that make up about 15 percent of the human genome, have been maintained throughout the entire history of mammals, and are present in every species of mammal that has been carefully examined. Our identification of a large group of rodents in which L1 elements quit transposing about 8.5 MYA - the only mammals so far known to lack active L1s - will allow us to examine some of the hypothesized impacts of s on genome organization. Possible consequences of L1 extinction include both potential positive and negative effects on the activity of other transposable elements, and a disruption of X inactivation in females (the Lyon Repeat Hypothesis). We will also exploit other pertinent """"""""experiments of nature"""""""" in dissecting the plasticity of mamma L1an genome organization. The first specific aim is to develop a comparative model system for studies of a mammalian genome without current L1 activity. The rice rat Oryzomys will serve as the L1-negative system and the cotton rat Sigmodon as the L1-positive control for ongoing studies of the impact of L1 activity on the mamma L1an genome. We will examine the global effects of L1 extinction on the genome and determine the timing and tempo of L1 quiescence and extinction. The second specific aim is to test the Lyon Repeat Hypothesis, which suggests that L1s function in X chromosome inactivation. This hypothesis is supported by the accumulation of Lls on the X chromosome and deficiency in regions that escape or are resistant to inactivation. We will examine the impact of L1 extinction on X chromosome inactivation in the sigmodontine rodents by looking at the evolution of the XIST gene and the expression of X linked genes. We will also continue our characterization of L1 elements throughout mammals, and examine XIST and L1 in mammals with unusual sex determining mechanisms or radical changes in the X chromosome.
| Yang, Lei; Brunsfeld, John; Scott, LuAnn et al. (2014) Reviving the dead: history and reactivation of an extinct l1. PLoS Genet 10:e1004395 |
| Erickson, Issac K; Cantrell, Michael A; Scott, LuAnn et al. (2011) Retrofitting the genome: L1 extinction follows endogenous retroviral expansion in a group of muroid rodents. J Virol 85:12315-23 |
