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. 1994;40(6):425-36. doi: 10.1007/BF00177825.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cercopithecidae / genetics*
  • Cercopithecidae / virology
  • Complement C4 / genetics*
  • DNA
  • DNA, Viral
  • Genetic Variation
  • Genome, Human
  • Humans
  • Introns
  • Molecular Sequence Data
  • Mutation
  • Recombination, Genetic
  • Repetitive Sequences, Nucleic Acid
  • Retroviridae / genetics*
  • Sequence Alignment
  • Species Specificity


  • Complement C4
  • DNA, Viral
  • DNA

Associated data

  • GENBANK/L38796
  • GENBANK/L38797
  • GENBANK/L38798
  • GENBANK/L38799
  • GENBANK/L38800
  • GENBANK/L38801
  • GENBANK/L38802
  • GENBANK/L38803
  • GENBANK/L38804
  • GENBANK/L38805
  • GENBANK/L38806
  • GENBANK/L38807
  • GENBANK/U07851
  • GENBANK/U07852
  • GENBANK/U07853
  • GENBANK/U07854
  • GENBANK/U07855
  • GENBANK/U07856