Evolutionary analysis at the molecular level provide new tools to biology when considering the action of natural selection in genes and sets of genes in their functional setting of physiological pathways. Their analysis is illuminating by one hand the molecular bases of complex adaptations and, moreover, may help in advancing at a higher pace the basic understanding of function at the gene-product (or protein) level. These processes can be seen comparing genome data of different species or of populations within a single species: selection at large or short scale.

The initial point is the interest of detecting natural selection in the form of positive (or adaptive) selection and purifying (or negative) selection. From the theoretical models now it is possible to interrogate whole genomes in the search of footprints of selection, among which there must lay the specific adaptations that define a species or a population. A new method that gathers information of many others will be presented.

Comparative analysis of selective pressures on sets of genes involved in a complex pathway or functional network may help disentangle the fine tuned purifying selection pressures that may be converted in terms of “biological importance” or relative dispensability in sets of genes. Results in functional networks and gene families show differences in selective pressures (and thus in function) that are not being detected by standard experimental methods.

As genes function in the context of molecular networks, with some occupying more important positions than others and thus being likely to be under stronger selective pressures, it is possible to interrogate how selection is distributes across the different parts of molecular networks. These analyses are telling us how evolution is shaping complex molecular pathways and networks, as the emerging function is a function of complex interactions. 

These analyses may be undertaken at the pathway level (with a low number of interacting units but a very detailed molecular knowledge) to relate selection and the specificity of the reactions and function, or at the general level of all interactions among proteins. At the level of the human interactome, selection does not act equally at short or long time depth: genes with higher centralities are more likely to have been targeted by recent positive selection during recent human evolution. These 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 intra-specific adaptive leaps affecting key network genes, followed by fine-tuning adaptations in less important network regions.

At the end the proposal says that population genetics is fundamental for understanding evolution and that the adaptive landscapes are NOT as we were told, but something like Montserrat or Meteora:

Reference Article: Luisi P, Alvarez-Ponce D, Pybus M, Fares M, Bertranpetit J*, and Laayouni H* (2015). Positive selection in the human protein-protein interaction network. Genome Biology and Evolution