Network-level molecular evolutionary analysis of the insulin/TOR signal transduction pathway across 12 Drosophila genomes
- 13 January 2009
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 19 (2), 234-242
- https://doi.org/10.1101/gr.084038.108
Abstract
Biological function is based on complex networks consisting of large numbers of interacting molecules. The evolutionary properties of molecular networks and, in particular, the impact of network architecture on the sequence evolution of its individual components are, nonetheless, still poorly understood. Here, we conducted a fine-scale network-level molecular evolutionary analysis of the insulin/TOR pathway across 12 species of Drosophila. We found that the insulin/TOR pathway components are completely conserved across these species and that two genes located at major network branch points show evidence for positive selection. Remarkably, we detected a gradient in the strength of purifying selection along the pathway, increasing from the upstream to the downstream genes. We also found that physically interacting proteins tend to have more similar levels of selective constraint, even though this feature might represent a byproduct of the correlation between selective constraint and the pathway position. Our results clearly indicate that the levels of functional constraint do depend on the position of the proteins in the pathway and, consequently, the architecture of the pathway constrains gene sequence evolution.Keywords
This publication has 54 references indexed in Scilit:
- Evolution of genes and genomes on the Drosophila phylogenyNature, 2007
- Population Genomics: Whole-Genome Analysis of Polymorphism and Divergence in Drosophila simulansPLoS Biology, 2007
- Using FlyAtlas to identify better Drosophila melanogaster models of human diseaseNature Genetics, 2007
- FlyBase: genomes by the dozenNucleic Acids Research, 2006
- Widespread Discordance of Gene Trees with Species Tree in Drosophila: Evidence for Incomplete Lineage SortingPLoS Genetics, 2006
- A Protein Interaction Map of Drosophila melanogasterScience, 2003
- dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1Nature, 2002
- The Genome Sequence of Drosophila melanogasterScience, 2000
- Ribosomal S6 Kinase Signaling and the Control of TranslationExperimental Cell Research, 1999
- The ‘effective number of codons’ used in a geneGene, 1990