Natural selection in functional pathways: an approach to understand natural selection within the complexity of life

BEGOÑA DOBON; MAYUKH MONDAL; MARC PYBUS; PIERRE LUISI; GIOVANNI M. DALL'OLIO; LUDOVICA MONTANUCCI; HAFID LAAYOUNI; JAUME BERTRANPETIT

Cold Spring Harbour

Encuentro; THE BIOLOGY OF GENOMES; 2016

Cold Spring Harbor Laboratory

One of the interesting evolutionary challenges is to discover the genetic bases of adaptive phenotypes, but the strongest challenges are complex adaptations. Some are being solved throughthe genetic analysis for specific adaptations, even for complex traits (like the short stature of Negritos), opening the field for complexity.Gene products function in molecular networks, as such, the position within the network may determine the strength of selection applied to the gene. This analysis indicates how evolution is shaping the complex interactions inherent to molecular pathways and networks. The analysis may be applied to the pathway level (with a low number of interacting units but a very detailed molecular knowledge), the entire metabolome, or even the whole interactome. We present here all these cases in order to relate selection to the specificity of reactions and their function.At the level of the human interactome, selection has not acted equally throughout evolutionary history: genes with higher number of interactions are more likely to have been targeted by recent positive selection during recent human evolution. Our results indicate that the relationship between centrality and the impact of adaptive evolution highly depends on the evolutionary time-scale. Most likely, network adaptation occurs through intraspecific adaptive leaps affecting key network genes, followed by the fine tuning of adaptations in less important network regions.This analysis goes beyond the identification of single cases of adaptation and opens the scope of understanding how natural selection works within the biomolecular complexity of life.