Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, SE-752 36 Uppsala, Sweden.
Genetics. 2021 Feb 9;217(2). doi: 10.1093/genetics/iyaa027.
Drosophila telomeres have been maintained by three families of active transposable elements (TEs), HeT-A, TAHRE, and TART, collectively referred to as HTTs, for tens of millions of years, which contrasts with an unusually high degree of HTT interspecific variation. While the impacts of conflict and domestication are often invoked to explain HTT variation, the telomeres are unstable structures such that neutral mutational processes and evolutionary tradeoffs may also drive HTT evolution. We leveraged population genomic data to analyze nearly 10,000 HTT insertions in 85 Drosophila melanogaster genomes and compared their variation to other more typical TE families. We observe that occasional large-scale copy number expansions of both HTTs and other TE families occur, highlighting that the HTTs are, like their feral cousins, typically repressed but primed to take over given the opportunity. However, large expansions of HTTs are not caused by the runaway activity of any particular HTT subfamilies or even associated with telomere-specific TE activity, as might be expected if HTTs are in strong genetic conflict with their hosts. Rather than conflict, we instead suggest that distinctive aspects of HTT copy number variation and sequence diversity largely reflect telomere instability, with HTT insertions being lost at much higher rates than other TEs elsewhere in the genome. We extend previous observations that telomere deletions occur at a high rate, and surprisingly discover that more than one-third do not appear to have been healed with an HTT insertion. We also report that some HTT families may be preferentially activated by the erosion of whole telomeres, implying the existence of HTT-specific host control mechanisms. We further suggest that the persistent telomere localization of HTTs may reflect a highly successful evolutionary strategy that trades away a stable insertion site in order to have reduced impact on the host genome. We propose that HTT evolution is driven by multiple processes, with niche specialization and telomere instability being previously underappreciated and likely predominant.
果蝇的端粒已经被三个活跃的转座元件（TEs）家族——HeT-A、TAHRE 和 TART——维持了数千万年，这些元件被统称为 HTTs，这与 HTTs 种间高度变异形成了鲜明对比。虽然冲突和驯化的影响常常被用来解释 HTT 的变异，但端粒是不稳定的结构，因此中性突变过程和进化权衡也可能驱动 HTT 的进化。我们利用群体基因组数据，分析了 85 个黑腹果蝇基因组中近 10000 个 HTT 插入，并将其变异与其他更典型的 TE 家族进行了比较。我们观察到，HTTs 和其他 TE 家族偶尔会发生大规模的拷贝数扩增，这表明 HTTs 与它们的野生表亲一样，通常受到抑制，但一旦有机会，它们就会接管。然而，HTTs 的大规模扩增并不是由任何特定的 HTT 亚家族的失控活动引起的，也与端粒特化的 TE 活动无关，如果 HTTs 与它们的宿主之间存在强烈的遗传冲突，情况可能就是如此。我们认为，与其说是冲突，不如说是 HTT 拷贝数变异和序列多样性的独特方面在很大程度上反映了端粒的不稳定性，与基因组其他地方的其他 TE 相比，HTT 的插入丢失率要高得多。我们扩展了之前关于端粒缺失率很高的观察结果，并令人惊讶地发现，超过三分之一的缺失似乎并没有通过 HTT 插入得到修复。我们还报告说，一些 HTT 家族可能会被整个端粒的侵蚀优先激活，这意味着存在特定于 HTT 的宿主控制机制。我们进一步认为，HTTs 持续的端粒定位可能反映了一种非常成功的进化策略，它牺牲了一个稳定的插入位点，以减少对宿主基因组的影响。我们提出，HTT 的进化是由多种过程驱动的，以前对生态位特化和端粒不稳定性的认识不足，但这两种过程可能是主要因素。
