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Evolution of mouse immunoglobulin lambda genes.

E Selsing, J Miller, R Wilson

    Proceedings of the National Academy of Sciences of the United States of America
    |August 1, 1982
    PubMed
    Summary
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    Researchers sequenced mouse lambda genes, revealing evolutionary relationships and duplication events. This study clarifies gene structures and evolutionary history, providing insights into mammalian gene evolution.

    Area of Science:

    • Immunogenetics
    • Molecular Evolution
    • Genomics

    Background:

    • The mouse genome contains four constant region lambda (C lambda) and two variable region lambda (V lambda) genes.
    • Understanding the organization and evolutionary history of these genes is crucial for comprehending immunoglobulin diversity.

    Purpose of the Study:

    • To isolate and sequence all six mouse lambda genes.
    • To elucidate the evolutionary relationships and duplication events of mouse C lambda and V lambda genes.
    • To correct previous sequence errors and provide a comprehensive analysis of lambda gene organization.

    Main Methods:

    • Isolation of Charon 4A clones containing all six lambda genes from a BALB/c germ-line library.
    • DNA sequencing of C lambda 2, C lambda 3, and C lambda 4 genes.

    Related Experiment Videos

  • Restriction mapping and electron microscopy for gene relationship analysis.
  • Heteroduplex analysis to determine homology between gene clusters.

    • Main Results:

    • DNA sequences for C lambda 2, C lambda 3, and C lambda 4 genes were determined, with corrections to C lambda 1 sequences.
    • Two gene clusters, JC lambda 3--JC lambda 1 and JC lambda 2--JC lambda 4, exhibit homology in their J and C regions.
    • V lambda 1 and V lambda 2 genes show significant homology in their 5' flanking regions, with large inverted repeats identified.
    • Analysis suggests ancestral JC lambda gene duplication events occurred during early mammalian evolution and after mouse-human speciation.

    Conclusions:

    • The mouse lambda gene clusters evolved through ancient duplications of primordial JC lambda genes.
    • The JC lambda x--JC lambda gene cluster duplicated post-mouse/human speciation, leading to the current JC lambda 3--JC lambda 1 and JC lambda 2--JC lambda 4 configurations.
    • C lambda 4 is a pseudogene that became inactive around the time of ancestral JC lambda x--JC lambda y cluster duplication.
    • V lambda gene evolution suggests a simultaneous or closely related duplication event with the JC lambda cluster, possibly involving recent duplications or gene conversion.