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The dichotomous size variation of human complement C4 genes is mediated by a novel family of endogenous retroviruses, which also establishes species-specific genomic patterns among Old World primates

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Abstract

The human complement C4 genes in the HLA exhibit an unusual, dichotomous size polymorphism and a four-gene, modular variation involving novel gene RP, complement C4, steroid 21-hydroxylase (CYP21), and tenascin-like Gene X (RCCX). The C4 gene size dichotomy is mediated by an endogenous retrovirus, HERV-K(C4). Nearly identical sequences for this retrotransposon are present precisely at the same location in the long C4 genes from the tandem RCCX Module I and Module II. Specific nucleotide substitutions between the long and short C4 genes have been identified and used for diagnosis. Southern blot analyses revealed that HERV-K(C4) is present at more than 30 locations in the human genome, exhibits variations in the population, and its analogs exist in the genomes of Old World primates with species-specific patterns. Evidence of intrachromosomal recombination between the two long terminal repeats of HERV-K(C4) is found near the huntingtin locus on chromosome 4. It is possible that members of HERV-K(C4) are involved in genetic instabilities including the RCCX modules, and in protecting the host genome from retroviral attack through an antisense strategy.

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Authors and Affiliations

  1. Children's Hospital Research Foundation, 43205, Columbus, OH, USA

    Andrew W. Dangel, Anna R. Mendoza, Bradley J. Baker, Charles M. Daniel & C. Yung Yu

  2. The Ohio State University Biochemistry Program, 43210, Columbus, OH, USA

    C. D. Menachery, Bradley J. Baker, Lai-Chu Wu & C. Yung Yu

  3. Department of Pediatrics, The Ohio State University, 700 Children's Drive, 43205, Columbus, OH, USA

    Bradley J. Baker & C. Yung Yu

  4. Department of Pathology, Harvard Medical School, 02165, Boston, MA, USA

    Michael C. Carroll

  5. Departments of Internal Medicine and Medical Biochemistry, The Ohio State University, 43210, Columbus, OH, USA

    Lai-Chu Wu

  6. Department of Medical Microbiology and Immunology, The Ohio State University, 43210, Columbus, OH, USA

    C. Yung Yu

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  1. Andrew W. Dangel
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Dangel, A.W., Mendoza, A.R., Menachery, C.D. et al. The dichotomous size variation of human complement C4 genes is mediated by a novel family of endogenous retroviruses, which also establishes species-specific genomic patterns among Old World primates. Immunogenetics 40, 425–436 (1994). https://doi.org/10.1007/BF00177825

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  • DOI: https://doi.org/10.1007/BF00177825

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