Faculty of Biology, Microbiology, Ludwig Maximilian University of Munich, Munich, Germany.
Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland.
Mol Biol Evol. 2024 Sep 4;41(9). doi: 10.1093/molbev/msae180.
Prolines cause ribosomes to stall during translation due to their rigid structure. This phenomenon occurs in all domains of life and is exacerbated at polyproline motifs. Such stalling can be eased by the elongation factor P (EF-P) in bacteria. We discovered a potential connection between the loss of ancestral EF-P, the appearance of horizontally transferred EF-P variants, and genomic signs of EF-P dysfunction. Horizontal transfer of the efp gene has occurred several times among bacteria and is associated with the loss of highly conserved polyproline motifs. In this study, we pinpoint cases of horizontal EF-P transfer among a diverse set of bacteria and examine genomic features associated with these events in the phyla Thermotogota and Planctomycetes. In these phyla, horizontal EF-P transfer is also associated with the loss of entire polyproline motif-containing proteins, whose expression is likely dependent on EF-P. In particular, three proteases (Lon, ClpC, and FtsH) and three tRNA synthetases (ValS, IleS1, and IleS2) appear highly sensitive to EF-P transfer. The conserved polyproline motifs within these proteins all reside within close proximity to ATP-binding-regions, some of which are crucial for their function. Our work shows that an ancient EF-P dysfunction has left genomic traces that persist to this day, although it remains unclear whether this dysfunction was strictly due to loss of ancestral EF-P or was related to the appearance of an exogenous variant. The latter possibility would imply that the process of "domesticating" a horizontally transferred efp gene can perturb the overall function of EF-P.
脯氨酸因其刚性结构导致核糖体在翻译过程中停滞。这种现象发生在所有生命领域，并且在多脯氨酸基序中更为严重。这种停滞可以通过细菌中的伸长因子 P（EF-P）缓解。我们发现了祖先 EF-P 丧失、水平转移的 EF-P 变体出现以及 EF-P 功能障碍的基因组迹象之间的潜在联系。efp 基因在细菌中的水平转移已经发生了多次，并且与高度保守的多脯氨酸基序的丧失有关。在这项研究中，我们确定了一组不同细菌中 EF-P 水平转移的情况，并研究了与 Thermotogota 和 Planctomycetes 门中这些事件相关的基因组特征。在这些门中，EF-P 的水平转移也与整个多脯氨酸基序蛋白的丧失有关，这些蛋白的表达可能依赖于 EF-P。特别是，三种蛋白酶（Lon、ClpC 和 FtsH）和三种 tRNA 合成酶（ValS、IleS1 和 IleS2）似乎对 EF-P 转移非常敏感。这些蛋白质中的保守多脯氨酸基序都位于 ATP 结合区域附近，其中一些对于它们的功能至关重要。我们的工作表明，古老的 EF-P 功能障碍留下了至今仍存在的基因组痕迹，尽管尚不清楚这种功能障碍是严格由于祖先 EF-P 的丧失还是与外源变体的出现有关。后一种可能性意味着“驯化”水平转移的 efp 基因的过程可能会扰乱 EF-P 的整体功能。
