Picolo Floriane, Bardin Jérémie, Laurin Michel, Piégu Benoît, Monget Philippe
PCR, UMR85, INRAE, CRNS, IFCE, Université de Tours, Nouzilly F-37380, France.
CR2P "Centre de Recherches sur la Paléo-biodiversité et les Paléo-environnements", UMR 7207, CNRS/MNHN, Muséum National d'Histoire Naturelle, Sorbonne Université, Paris, France.
Genome Biol Evol. 2025 Apr 3;17(4). doi: 10.1093/gbe/evaf034.
In this work, we investigate whether the construction of signaling pathways during evolution follows a deterministic law through a study of the eventual link between age of appearance in the tree of life and position in the signaling pathway of genes involved in these pathways. We use the 47 human signaling pathways described in the Kyoto Encyclopedia of Genes and Genomes and investigate the orthologs of these genes in 315 animal species plus a yeast taxon, representing 15 large clades. Many genes appear on two key branches: those between the last common ancestor of Opisthokonta and Metazoa and between Deuterostomia and Chordata. We look for a link between the age of appearance of an upstream A gene and that of its downstream B partner. We observe that for all the interactions of two partners, only 20.6% of the corresponding genes arose simultaneously in the tree of life, 40.7% being called "backward" (i.e. B appearing before A) and 38.7% "forward" (A appearing before B). For 16 of the 47 pathways, there is a positive correlation between the age rank difference between interacting partner genes and the position of the corresponding proteins in the pathway: the more upstream a protein is involved in the pathway, the greater the rank difference is (the correlation, positive or negative, is not significant for 30 pathways). For the sole insulin signaling pathway, this correlation is negative. Moreover, by permutation test, we find that 14 of the 47 observed pathway contained larger modules (subset respecting a homogeneous appearance pattern) than expected by chance alone. Finally, for 20 of the 47 pathways, the construction scenario appears to be random, as these pathways do not validate any of our statistical tests (permutation tests on interaction direction and module sizes as well as correlation test on pathway position and age rank). Given that only 14.9% of the tests are significant and that significant effects are different among pathways, we conclude that there is no deterministic rule in the establishment of the pathways herein studied or that the patterns have been obscured by subsequent transformations.
在这项研究中，我们通过研究基因在生命之树中的出现时间与参与这些信号通路的基因在信号通路中的位置之间的最终联系，来探究进化过程中信号通路的构建是否遵循确定性规律。我们使用了《京都基因与基因组百科全书》中描述的47条人类信号通路，并研究了这些基因在315种动物物种以及一个酵母分类单元中的直系同源基因，这些物种代表了15个大的进化枝。许多基因出现在两个关键分支上：一个是后口动物和后生动物的最后共同祖先之间的分支，另一个是后口动物和脊索动物之间的分支。我们寻找上游A基因与其下游B伙伴的出现时间之间是否存在联系。我们观察到，对于所有两个伙伴的相互作用，在生命之树中，只有20.6%的相应基因是同时出现 的，40.7%被称为“反向”（即B出现在A之前），38.7%为“正向”（A出现在B之前）。在47条通路中的16条中，相互作用的伙伴基因之间的年龄排名差异与相应蛋白质在通路中的位置之间存在正相关：蛋白质在通路中参与得越上游，排名差异就越大（对于30条通路，正相关或负相关均不显著）。对于唯一的胰岛素信号通路，这种相关性为负。此外，通过置换检验，我们发现47条观察到的通路中有14条包含比仅由随机因素预期的更大的模块（遵循均匀出现模式的子集）。最后，对于47条通路中的20条，构建情况似乎是随机的，因为这些通路没有通过我们的任何统计检验（关于相互作用方向和模块大小的置换检验以及关于通路位置和年龄排名的相关性检验）。鉴于只有14.9%的检验是显著的，并且显著效应在不同通路之间存在差异，我们得出结论，在所研究的通路建立过程中没有确定性规则，或者这些模式已被后续的转变所掩盖。
