As much as 50% of the typical mammalian genome consists of retrotransposed sequences, dominated by LINE-1 and various types of SINE retrotransposons. LINE-1 encodes genes for its own retrotransposition, but is also parasitized by SINEs for their movement. LINE-1 has been co-evolving with its mammalian hosts for at least 170 million years and has had major impacts on their evolution. However, two LINE-1 extinction events have been documented, affecting 9% of mammalian species. Shutting down LINE-1 activity should result in a simultaneous silencing of SINEs. However, in a LINE-1 extinction event in South American rodents, the extinction of the B1 family of SINEs was unexpectedly found to precede the extinction of LINE-1. Reconstruction of the common ancestor of the extinct LINE-1 and B1 and analysis of their interactions in a tissue culture assay will be used to explore the mechanism underlying their extinction.
Although retrotransposons like LINEs and SINEs have had large impacts on mammalian evolution, our knowledge of them is limited to the study of sequenced genomes and work in model organisms. The arms race between LINE-1 and B1, or autonomous and the corresponding non-autonomous transposons in a broader sense, has been investigated by computational simulations, but empirical data are scarce. Tools developed to understand the mechanism of transpositions in humans and model organisms will be extended to a non-model system with a unique evolutionary history. This proposal will contribute to the larger picture of mammalian genome evolution and transposable element regulation.
Transposable elements, also known as jumping genes, account for approximately half of a typical mammalian genome. They increase in copy number because the majority of them mobilize within the host genomes in a copy-paste fashion. LINE (Long INterspersed Element) and SINE (Short INterspersed Element) are two of the largest families of mammalian transposable elements and together account for more than half of all mammalian transposable elements. LINEs encode genes required for their own mobilization, while SINEs are totally dependent on the genes of LINEs. L1 (LINE-1) is the dominant LINE family in placental and marsupial mammals, while dominating SINE families diverge between different orders of mammals. In rodents, B1 is the major SINE family. Despite the fact that LINEs and SINEs compromise a quarter of a mammalian genome and they are occasionally co-adapt to serve host functions, they are found to have lost their activity at least eight million years ago in a group of species-rich South American rodents. This group includes about 7% of all mammalian species. Given B1s are dependent on L1, one would expect that their extinction to be simultaneous. We dissected the evolutionary history of L1 and B1 in the sigmodontine rodents and found that the last waves of L1 and B1 mobilizations preceding their respective extinction were the strongest in the detectable evolutionary history. Unlike the originally hypothesized scenario where B1 extinction is caused by L1 quiescence, the extinction time window of B1 corresponds to the last and strongest wave of L1 mobilization. The tempo of L1 and B1 mobilization before their extinction hints possible trigger of strong host regulation due to their volatile activity.
