  The antibody repertoire of each individual is continuously updated by the
evolutionary process of B cell receptor mutation and selection. It has recently
become possible to gain detailed information concerning this process through
high-throughput sequencing. Here, we develop modern statistical molecular
evolution 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 process 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 empirical Bayes estimators that compare the
evolution of in-frame and out-of-frame rearrangements. We use this new method
to derive a per-residue map of selection, which provides a more nuanced view of
the constraints on framework and variable regions.
