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

Abstract

Incremental selection within a population, defined as limited fitness changes following mutation, is an important aspect of many evolutionary processes. Strongly advantageous or deleterious mutations are detected using the synonymous to non-synonymous mutations ratio. However, there are currently no precise methods to estimate incremental selection. We here provide for the first time such a detailed method and show its precision in multiple cases of microevolution. 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 propose to measure the log of the ratio between the number of leaves in lineage trees branches following synonymous and non-synonymous mutations. The method requires a high enough number of sequences, and a large enough number of independent mutations. It assumes that all mutations are independent events. It does not require of a baseline model and is practically not affected by sampling biases. We show the method's wide applicability by testing it on multiple cases of micro-evolution. We 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.

The analysis of clonal expansions in normal and autoimmune B cell repertoires

“…Analysing the patterns of these lineages can give insights into the diversification and selection processes that lead to clonal evolution [78,79]. Different lineage analyses have led to the calculation of the mutation rate of SHM [80] and as metrics of the specific selection pressure on a set of mutations in a given branch or at the root of the lineage [81,82].…”