Genes Encoding Intracellular Signaling Proteins in Animals Originated Along with Metazoa and Chordata: Chance or Necessity?

Abstract

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.