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arXiv · 1403.3066

Quantifying evolutionary constraints on B cell affinity maturation

Connor O. McCoy·Trevor Bedford·Vladimir N. Minin·Philip Bradley·Harlan Robins·Frederick A. Matsen IV
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Abstract

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.

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Connor O. McCoy, Trevor Bedford, Vladimir N. Minin, Philip Bradley, Harlan Robins, Frederick A. Matsen IV. 2014-03-12. Quantifying evolutionary constraints on B cell affinity maturation. https://doi.org/10.1098/rstb.2014-0244

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