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Uneven distribution of repetitive trinucleotide motifs in human immunoglobulin heavy variable genes

Lantto, Johan LU and Ohlin, Mats LU (2002) In Journal of Molecular Evolution 54(3). p.346-353
Abstract
Insertions and deletions of entire codons have recently been discovered as a mechanism by which B cells, in addition to conventional base substitution, evolve the antibodies produced by their immunoglobulin genes. These events frequently seem to involve repetitive sequence motifs in the antibody-encoding genes, and it has been suggested that they occur through polymerase slippage. In order to better understand the process of codon deletion, we have analyzed the human immunoglobulin heavy variable (IGHV) germline gene repertoire for the presence of trinucleotide repeats. Such repeats would ensure that the reading frame is maintained in the case of a deletional event, as slippage over multiples of three bases would be favored. We demonstrate... (More)
Insertions and deletions of entire codons have recently been discovered as a mechanism by which B cells, in addition to conventional base substitution, evolve the antibodies produced by their immunoglobulin genes. These events frequently seem to involve repetitive sequence motifs in the antibody-encoding genes, and it has been suggested that they occur through polymerase slippage. In order to better understand the process of codon deletion, we have analyzed the human immunoglobulin heavy variable (IGHV) germline gene repertoire for the presence of trinucleotide repeats. Such repeats would ensure that the reading frame is maintained in the case of a deletional event, as slippage over multiples of three bases would be favored. We demonstrate here that IGHV genes specifically carry repetitive trinucleotide motifs in the complementarity-determining regions (CDR) 1 and 2, thus making these parts of the genes that encode highly flexible structures particularly prone to functional deletions. We propose that the human IGHV repertoire carries inherent motifs that allow an antibody response to develop efficiently by targeting codon deletion events to the parts of the molecule that are likely to be able to harbor such modifications. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
variable genes, repetitive sequences, mutation, IGHV, antibody, deletion
in
Journal of Molecular Evolution
volume
54
issue
3
pages
346 - 353
publisher
Springer
external identifiers
  • wos:000173928400006
  • pmid:11847560
  • scopus:0036183040
ISSN
0022-2844
DOI
10.1007/s00239-001-0049-2
language
English
LU publication?
yes
id
8fcb3b69-19e3-4501-8fce-a66a00faf6b6 (old id 343159)
date added to LUP
2007-11-07 16:03:55
date last changed
2017-12-10 03:45:18
@article{8fcb3b69-19e3-4501-8fce-a66a00faf6b6,
  abstract     = {Insertions and deletions of entire codons have recently been discovered as a mechanism by which B cells, in addition to conventional base substitution, evolve the antibodies produced by their immunoglobulin genes. These events frequently seem to involve repetitive sequence motifs in the antibody-encoding genes, and it has been suggested that they occur through polymerase slippage. In order to better understand the process of codon deletion, we have analyzed the human immunoglobulin heavy variable (IGHV) germline gene repertoire for the presence of trinucleotide repeats. Such repeats would ensure that the reading frame is maintained in the case of a deletional event, as slippage over multiples of three bases would be favored. We demonstrate here that IGHV genes specifically carry repetitive trinucleotide motifs in the complementarity-determining regions (CDR) 1 and 2, thus making these parts of the genes that encode highly flexible structures particularly prone to functional deletions. We propose that the human IGHV repertoire carries inherent motifs that allow an antibody response to develop efficiently by targeting codon deletion events to the parts of the molecule that are likely to be able to harbor such modifications.},
  author       = {Lantto, Johan and Ohlin, Mats},
  issn         = {0022-2844},
  keyword      = {variable genes,repetitive sequences,mutation,IGHV,antibody,deletion},
  language     = {eng},
  number       = {3},
  pages        = {346--353},
  publisher    = {Springer},
  series       = {Journal of Molecular Evolution},
  title        = {Uneven distribution of repetitive trinucleotide motifs in human immunoglobulin heavy variable genes},
  url          = {http://dx.doi.org/10.1007/s00239-001-0049-2},
  volume       = {54},
  year         = {2002},
}