Substitution and site-specific selection driving B cell affinity maturation is consistent across individuals

Substitution and site-specific selection driving B cell affinity maturation is consistent across individuals

Connor O. McCoy, Trevor Bedford, Vladimir N. Minin, Harlan Robins, Frederick A. Matsen IV
(Submitted on 12 Mar 2014)

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 we find is dominated by purifying selection, though not uniformly so.

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