GenesThe Inference of Antigen Selection on Ig

Analysis of somatic mutations in V regions of Ig genes is important for understanding various biological processes. It is customary to estimate Ag selection on Ig genes by assessment of replacement (R) as opposed to silent (S) mutations in the complementary-determining regions and S as opposed to R mutations in the framework regions. In the past such an evaluation was performed using a binomial distribution model equation, which is inappropriate for Ig genes in which mutations have four different distribution possibilities (R and S mutations in the complementary-determining region and/or framework regions of the gene). In the present work, we propose a multinomial distribution model for assessment of Ag selection. Side-by-side application of multinomial and binomial models on 86 previously established Ig sequences disclosed 8 discrepancies, leading to opposite statistical conclusions about Ag selection. We suggest the use of the multinomial model for all future analysis of Ag selection. The Journal of Immunology, 2000, 165: 5122–5126. we used the Rf FR and Rf CDR values implied in these articles. Recalculation of these values resulted in slightly different Rf values for some of the V H genes. The discrepancies most probably result from the use of slightly different germline sequences before the final sequence of the V H gene locus was established and from the use of sequences in which there are poly-morphic variations. For the future calculation of the Rf values, we suggest using our JAVA applet, available at http://www-stat.stanford.edu/imuuno-globin, which calculates the Rf values for imported germline sequences.