Identification of a novel family of human endogenous retroviruses and characterization of one family member, HERV-K(C4), located in the complement C4 gene cluster.
We have identified a novel family of about 10-50 human endogenous retrovirus elements (HERVs) and have characterized one family member (HERV-KC4). This retrovirus element is integrated within intron 9 of and complement C4A genes and also in some C4B genes, and is a principal contribution to interlocus and interallelic length heterogeneity of C4 genes. The HERV-K(C4) sequence has a typical retrovirus structure with elements of gag, pol and env domains, flanked by two long terminal repeats (LTRs) and is similar to type A, B and D retroviruses. Multiple termination codons preclude the existence of long open reading frames, suggesting that the HERV-K(C4) sequence is no longer functional. Zoo blot hybridization reveals that New World monkeys appear to lack sequences similar to HERV-K(C4), suggesting that integration has occurred after the divergence of Old and New World monkeys. Retrotransposition of prototype viruses is presumed to have led to the amplification and integration of the members of the family in different loci, which in humans, appear to be dispersed over several chromosomes. The absence of the HERV-K(C4) element in some C4B genes in both humans and orangutangs indicate that the retrovirus inserted into the C4A gene after the duplication of the cluster. Subsequent spread of the HERV-K(C4) sequence to C4B genes presumably occurred by interlocus sequence exchange mechanisms, such as unequal crossover and gene conversion-like mechanisms.
Tassabehji
M
M
Department of Medical Genetics, University of Manchester, St Mary's Hospital, UK.
Strachan
T
T
Anderson
M
M
Campbell
R D
RD
Collier
S
S
Lako
M
M
D000818:Animals; D001483:Base Sequence; D002520:Cercopithecidae / Q000821:virology; D018388:Codon, Terminator; D003181:Complement C4 / Q000235:genetics*; D017124:Conserved Sequence; D018628:Gene Dosage; D005814:Genes, Viral / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D011148:Pongo pygmaeus / Q000821:virology; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D015183:Restriction Mapping; D012190:Retroviridae / Q000145:classification / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D015678:Viral Structural Proteins / Q000235:genetics
D018388:Codon, Terminator; D003181:Complement C4; D015678:Viral Structural Proteins