title: Molecular population genetics of the insulin/TOR signal transduction pathway: a network-level analysis in Drosophila melanogaster.
abstract: The IT-insulin/target of rapamycin (TOR)-signal transduction pathway is a relatively well-characterized pathway that plays a central role in fundamental biological processes. Network-level analyses of DNA divergence in Drosophila and vertebrates have revealed a clear gradient in the levels of purifying selection along this pathway, with the downstream genes being the most constrained. Remarkably, this feature does not result from factors known to affect selective constraint such as gene expression, codon bias, protein length, and connectivity. The present work aims to establish whether the selective constraint gradient detected along the IT pathway at the between-species level can also be observed at a shorter time scale. With this purpose, we have surveyed DNA polymorphism in Drosophila melanogaster and divergence from D. simulans along the IT pathway. Our network-level analysis shows that DNA polymorphism exhibits the same polarity in the strength of purifying selection as previously detected at the divergence level. This equivalent feature detected both within species and between closely and distantly related species points to the action of a general mechanism, whose action is neither organism specific nor evolutionary time dependent. The detected polarity would be, therefore, intrinsic to the IT pathway architecture and function.
authors.affiliation: Departament de Genètica, i Institut de Recerca de la Biodiversitat, Universitat de Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Alvarez-Ponce
authors.forename: Sara
authors.initials: S
authors.lastname: Guirao-Rico
authors.forename: Dorcas J
authors.initials: DJ
authors.lastname: Orengo
authors.forename: Carmen
authors.initials: C
authors.lastname: Segarra
authors.forename: Julio
authors.initials: J
authors.lastname: Rozas
authors.forename: Montserrat
authors.initials: M
authors.lastname: Aguadé
mesh_terms: D000818:Animals; D004247:DNA; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics*; D019143:Evolution, Molecular; D017344:Genes, Insect; D005828:Genetics, Population; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D016014:Linear Models; D011110:Polymorphism, Genetic; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; D004247:DNA; D011494:Protein Kinases; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases