Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

The targeting of somatic hypermutation

C J Jolly1, S D Wagner, C Rada

  • 1Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.

Seminars in Immunology
|June 1, 1996
PubMed
Summary

Somatic hypermutation in immunoglobulin V genes targets specific DNA hotspots, not randomly, to enhance antibody affinity. This strategic targeting, evident even in lower animals, evolved early in antigen receptor development.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Pregnancy outcome in free-ranging vervet monkeys (Cercopithecus aethiops).

American journal of primatology·2020
Same author

[Ankle-brachial index screening for peripheral artery disease in high cardiovascular risk patients. Prospective observational study of 370 asymptomatic patients at high cardiovascular risk].

Journal des maladies vasculaires·2016
Same author

A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment.

Cell death & disease·2016
Same author

Hybrid hybridomas and the production of bi-specific monoclonal antibodies.

Immunology today·2014
Same author

Novel CTCF binding at a site in exon1A of BCL6 is associated with active histone marks and a transcriptionally active locus.

Oncogene·2013
Same author

Characterisation of the wheat Mr 15000 "grain-softness protein" and analysis of the relationship between its accumulation in the whole seed and grain softness.

TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik·2013

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Somatic hypermutation (SHM) is crucial for adaptive immunity, generating antibody diversity.
  • SHM in immunoglobulin V genes is known to be non-random, with specific mutation 'hotspots' and 'coldspots'.

Purpose of the Study:

  • To investigate the distribution and significance of mutational hotspots and coldspots within immunoglobulin V genes.
  • To explore the role of DNA sequence and codon usage in directing SHM.
  • To determine if these patterns are conserved across species and evolved early in antigen receptor evolution.

Main Methods:

  • Analysis of nucleotide positions within immunoglobulin V genes.
  • Examination of DNA sequence and codon usage biases.
  • Comparative analysis of V genes across different animal species.

Related Experiment Videos

Main Results:

  • SHM is preferentially targeted to specific nucleotide positions (hotspots) within V genes, avoiding others (coldspots).
  • Coldspots often correlate with residues critical for V gene folding, while hotspots are frequently located in complementarity-determining regions (CDRs), particularly CDR1.
  • Conserved hotspots are also found at the base of framework region 3 (FR3).
  • Local DNA sequence and biased codon usage contribute to hotspot formation, indicating evolutionary adaptation for targeted mutation.
  • Similar patterns of mutational hotspots and biased codon usage are observed in V genes of lower animals.

Conclusions:

  • Immunoglobulin V gene evolution has optimized SHM targeting to specific regions, particularly CDRs, to enhance antibody affinity maturation.
  • The observed patterns suggest that strategic, non-templated mutation targeting evolved early in the evolution of antigen receptors.