Zdraljevic Stefan, Walter-McNeill Laura, Bruni Giancarlo N, Bloom Joshua S, Leighton Daniel H W, Collins J B, Marquez Heriberto, Alexander Noah, Kruglyak Leonid
Department of Human Genetics, University of California, Los Angeles, CA, USA.
Department of Biological Chemistry, University of California, Los Angeles, CA, USA.
bioRxiv. 2024 Nov 20:2024.04.26.591160. doi: 10.1101/2024.04.26.591160.
Toxin-antidote elements (TAs) are selfish DNA sequences that bias their transmission to the next generation. TAs typically consist of two linked genes: a toxin and an antidote. The toxin kills progeny that do not inherit the TA, while the antidote counteracts the toxin in progeny that inherit the TA. We previously discovered two TAs in that follow the canonical TA model of two linked genes: and . Here, we report a new TA that exists in three distinct states across the population. The canonical TA, which is found in isolates from the Hawaiian islands, consists of two genes that encode a maternally deposited toxin (MLL-1) and a zygotically expressed antidote (SMLL-1). The toxin induces larval lethality in embryos that do not inherit the antidote gene. A second version of the TA has lost the toxin gene but retains a partially functional antidote. Most isolates, including the standard laboratory strain N2, carry a highly divergent allele of the toxin that has retained its activity, but have lost the antidote through pseudogenization. We show that the N2 toxin allele has acquired mutations that enable piRNA binding to initiate MUT-16-dependent 22G small RNA amplification that targets the transcript for degradation. The N2 haplotype represents the first naturally occurring unlinked toxin-antidote system where the toxin is post-transcriptionally suppressed by endogenous small RNA pathways.
毒素-解毒剂元件（TAs）是一类自私的DNA序列，它们会偏向于将自身传递给下一代。TAs通常由两个连锁基因组成：一个毒素基因和一个解毒剂基因。毒素会杀死未继承TA的后代，而解毒剂则会抵消继承了TA的后代体内的毒素。我们之前在[具体物种]中发现了两个遵循两个连锁基因的经典TA模型的TAs：[TA1名称]和[TA2名称]。在这里，我们报告了一种新的TA，它在[具体物种]群体中以三种不同状态存在。在来自夏威夷群岛的分离株中发现的经典TA由两个基因组成，这两个基因编码一个母系沉积的毒素（MLL-1）和一个合子表达的解毒剂（SMLL-1）。毒素会在未继承解毒剂基因的胚胎中诱导幼虫致死。TA的第二个版本已经失去了毒素基因，但保留了部分功能的解毒剂。大多数[具体物种]分离株，包括标准实验室菌株N2，携带一个具有活性的高度分化的毒素等位基因，但通过假基因化失去了解毒剂。我们表明，N2毒素等位基因获得了一些突变，这些突变使piRNA能够结合，从而启动依赖MUT-16的22G小RNA扩增，该扩增靶向转录本进行降解。N2单倍型代表了第一个自然发生的非连锁毒素-解毒剂系统，其中毒素通过内源性小RNA途径在转录后受到抑制。
