Molecular Biology and Evolution, Vol 14, 637-643, Copyright © 1997 by Society for Molecular Biology and Evolution
TB Kepler
Immunoglobulin genes experience Darwinian evolution twice. In addition to
the germline evolution all genes experience, immunoglobulins are subjected,
upon exposure to antigen, to somatic hypermutation. This is accompanied by
selection for high affinity to the eliciting antigen and frequently results
in a significant increase in the specificity of the responding population.
The hypermutation mechanism displays a strong sequence specificity. Thus
arises the opportunity to manipulate codon bias in a site-specific manner
so as to direct hypermutation to those parts of the gene that encode the
antigen-binding portions of the molecule and away from those that encode
the structurally conserved regions. This segregation of mutability would
clearly be advantageous; it would enhance the generation of potentially
useful variants while keeping mutational loss to acceptably low levels. But
it is not clear that the advantage gained would be large enough to produce
a measurable effect within the background stochasticity of the evolutionary
process. I have performed a pair of statistical tests to determine whether
site- specific codon bias in human immunoglobulin genes is correlated with
the sequence specificity of the somatic mutation mechanism. The sequence
specificity of the mutator was determined by analysis of a database of
published immunoglobulin intron sequences that had experienced somatic
mutation but not selection. The site-specific codon bias was determined by
analysis of published sequences of human germline immunoglobulin V genes.
Both tests strongly suggest that evolution has acted to enhance the
plasticity of immunoglobulin genes under somatic hypermutation.
ORIGINAL ARTICLE
Codon bias and plasticity in immunoglobulins
Department of Statistics, North Carolina State University, Raleigh 27695-8203, USA. kepler@unity.ncsu.edu
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