Transduction of the human gene FAM8A1 by endogenous retrovirus during primate evolution.
Capture of cellular mRNA by mobile elements has been an evolutionary catalyst for the spread of genes and a cause of cancer development. Here we present evidence that an orphan gene, FAM8A1 (family with sequence similarity 8), was captured by a retrovirus, followed by multiple retrotransposition events, during primate evolution between 45 and 58 million years ago. This represents the first record of cellular mRNA transduction in humans. The human gene is localized on chromosome 6p23 with five related pseudogenes (FAM8A2P-A6P), each inserted within a human endogenous retrovirus (HERV). Only the functional FAM8A1 gene is expressed and displays a ubiquitous mRNA and a testis-specific transcript present in the haploid phase of spermatogenesis. The structural features of the FAM8A1 pseudogenes include two short sequences of similarity between the FAM8A1 mRNA and the HERV sequences at both the 5' and 3' integration sites. These hallmarks suggest an alternative model to account for the capture of FAM8A1 cellular mRNA by HERV-K, involving illegitimate recombination events at the two sites of sequence similarity during reverse transcription. Unlike previous models, which assume at least one step of retroviral integration in the genome, our model is consistent with in vitro observations showing that multiple template switches occur among packaged viral transcripts. This leads to the speculation that, in some cases, cellular mRNAs may have been captured through similar processes involved in the retroviral life cycle.
Jamain
S
S
Laboratoire d 'Immunogénétique Humaine, INSERM E021, Institut Pasteur, 25, rue du Docteur Roux, Paris Cedex 15, 75724, France.
Girondot
M
M
Leroy
P
P
Clergue
M
M
Quach
H
H
Fellous
M
M
Bourgeron
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002417:Cattle; D002645:Chickens; D004247:DNA / Q000737:chemistry / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D020077:Endogenous Retroviruses / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D005785:Gene Conversion; D015870:Gene Expression; D022761:Gene Transfer, Horizontal; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011323:Primates / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution; D014426:Turtles; D014981:Xenopus
D018076:DNA, Complementary; C442863:FAM8A1 protein, human; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; D004247:DNA