Patterns of convergent somatic hypermutations in the adaptive immune response of Mus musculus

Abstract

We analyzed a dataset of 964 clonally unrelated murine antibodies for which structures have been deposited in the PDB. 454 of the 964 antibodies have gapless germline assignments and do not have excessive numbers of computationally identified somatic hypermutations (SHMs). About 5,500 SHMs were identified, of which approximately 3,500 are in the framework. We then searched for correlated convergent SHMs, i.e. groups of SHMs that arose independently in different antibodies but at the same sequence position and with the same germline and mature amino acid identity. A surprisingly large number of groups of correlated convergent SHMs were found. 329 antibodies share at least two, 161 antibodies share at least three, 87 antibodies share at least four, and 53 antibodies share at least five identical SHMs with another antibody in the dataset. We then analyzed whether any of the correlated SHMs are forming structural cluster. Approximately 400 clusters where CFWMs are located within 10 Å of each other were identified. 158 of these clusters are in the framework region. Identification of such structural clusters of correlated convergent SHMs may help identify adaptive mutations that act in an antigen-independent manner.