SUBSTITUTION AND SITE-SPECIFIC SELECTION DRIVING B CELL AFFINITY MATURATION IS CONSISTENT ACROSS INDIVIDUALS

ABSTRACT. The antibody repertoire of each individual is continuously updated by the evolutionary process of B cell receptor mutation and selection. It has re-cently become possible to gain detailed information concerning this process through high-throughput sequencing. Here, we develop modern statistical molecular evo-lution methods for the analysis of B cell sequence data, and then apply them to a very deep short-read data set of B cell receptors. We find that the substitution pro-cess is conserved across individuals but varies significantly across gene segments. We investigate selection on B cell receptors using a novel method that side-steps the difficulties encountered by previous work in differentiating between selection and motif-driven mutation; this is done through stochastic mapping and empiri-cal Bayes estimators that compare the evolution of in-frame and out-of-frame re-arrangements. We use this new method to derive a per-residue map of selection, which we find is dominated by purifying selection, though not uniformly so