Transduction of the human gene FAM8A1 by endogenous retrovirus during primate evolution

Capture of cellular mRNA by mobile elements has been an evolutionary cataly st for the spread of genes and a cause of cancer development. Here we prese nt evidence that an orphan gene, FAM8A1 (family with sequence similarity 8) , was captured by a retrovirus, followed by multiple retrotransposition eve nts, during primate evolution between 45 and 58 million years ago. This rep resents the first record of cellular mRNA transduction in humans. The human gene is localized on chromosome 6p23 with five related pseudogenes (FAM8A2 P-A6P), each inserted within a human endogenous retrovirus (HERV). Only the functional FAM8A1 gene is expressed and displays a ubiquitous mRNA and a t estis-specific transcript present in the haploid phase of spermatogenesis. The structural features of the FAM8A1 pseudogenes include two short sequenc es 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 ill egitimate recombination events at the two sites of sequence similarity duri ng 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 cas es, cellular mRNAs may have been captured through similar processes involve d in the retroviral life cycle.