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Published on: September 15, 2010
Predicting regional mutability in antibody V genes based solely on di- and trinucleotide sequence composition
G S Shapiro1, K Aviszus, D Ikle
1Department of Pediatrics, Division of Basic Sciences, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Somatic mutations in immunoglobulin V genes show a consistent sequence bias across species. This suggests a shared mutation mechanism influences antibody gene evolution in both mice and humans.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Somatic mutations in immunoglobulin V genes are crucial for antibody diversity.
- The distribution of these mutations is not random and suggests sequence-specific targeting.
Purpose of the Study:
- To investigate the sequence-specific mutational bias in immunoglobulin V genes across species.
- To determine if a common mutation mechanism underlies regional mutability patterns in human and mouse Ig V genes.
Main Methods:
- Analysis of di- and trinucleotide mutability patterns in intronic DNA of mouse JH and Jkappa clusters and human VH genes.
- Prediction of regional mutabilities in human and murine germline V genes using identified target preferences.
- Comparison of predicted mutabilities with empirical mutation data from nonproductively rearranged human VH genes.
Main Results:
- A shared di- and trinucleotide mutability preference pattern was identified in mouse and human Ig V genes, indicating a common mutation mechanism.
- Heavy chain genes in both species show higher predicted mutability in CDR1, CDR2, and FR3 compared to FR1 and FR2.
- Light chain genes exhibit an unexpected high mutability prediction for FR2.
Conclusions:
- A common mutation mechanism with regional bias exists for both heavy and light chain immunoglobulin V genes in mice and humans.
- Short nucleotide sequence composition qualitatively, but not quantitatively, explains the observed regional mutational preferences.
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