Estimate of Within Population Incremental Selection Through Branch Imbalance in Lineage Trees

Incremental selection within a population, defined as a limited fitness change following a mutation, is an important aspect of many evolutionary processes and can significantly affect a large number of mutations through the genome. Strongly advantageous or deleterious mutations are detected through the fixation of mutations in the population, using the synonymous to non-synonymous mutations ratio in sequences. There are currently to precise methods to estimate incremental selection occurring over limited periods. We here provide for the first time such a detailed method and show its precision and its applicability to the genomic analysis of selection. A special case of evolution is rapid, short term micro-evolution, where organism are under constant adaptation, occurring for example in viruses infecting a new host, B cells mutating during a germinal center reactions or mitochondria evolving within a given host. The proposed method is a novel mixed lineage tree/sequence based method to detect within population selection as defined by the effect of mutations on the average number of offspring. Specifically, we pro-pose to measure the log of the ratio between the number of leaves in lineage trees branches following synonymous and non-synonymous mutations. This method does not suffer from the need of a baseline model and is practically not affected by sampling biases. In order to show the wide applicability of this method, we apply it to multiple cases of micro-evolution, and show that it can detect genes and inter-genic regions using the selection rate and detect selection pressures in viral proteins and in the immune response to pathogens.