Survey of Human Genes of Retroviral Origin: Identification and Transcriptome of the Genes with Coding Capacity for Complete Envelope Proteins

Abstract

Sequences of retroviral origin occupy approximately 8% of the human genome. Most of these "retroviral" genes have lost their coding capacities since their entry into our ancestral genome millions of years ago, but some reading frames have remained open, suggesting positive selection. The complete sequencing of the human genome allowed a systematic search for retroviral envelope genes containing an open reading frame and resulted in the identification of 16 genes that we have characterized. We further showed, by quantitative reverse transcriptase PCR using specifically devised primers which discriminate between coding and noncoding elements, that all 16 genes are expressed in at least some healthy human tissues, albeit at highly different levels. All envelope genes disclose significant expression in the testis, three of them have a very high level of expression in the placenta, and a fourth is expressed in the thyroid. Besides their primary role as key molecules for viral entry, the envelope genes of retroviruses can induce cell-cell fusion, elicit immunosuppressive effects, and even protect against infection, and as such, endogenous retroviral envelope proteins have been tentatively identified in several reports as being involved in both normal and pathological processes. The present study provides a comprehensive survey of candidate genes and tools for a precise evaluation of their involvement in these processes.

Paleovirology of ‘ syncytins ’, retroviral env genes exapted for a role in placentation

“…Comprehensive screening for identifying human ERV (HERV) env genes with long open reading frames (ORFs) within the human genome disclosed 18 genes encoding a putative envelope protein [32,33]. Among those potentially functional, the first to be described was ERV3, a proviral gene specifically expressed in the placenta and conserved in the Hominoid and Old World monkey families [34].…”

Mobility and integration sites of a murine C57BL/6 melanoma endogenous retrovirus involved in tumor progression in vivo

“…One microgram of RNA was reverse transcribed using Moloney murine leukemia virus RT (Applied Biosystems) as described in Ref. 16. For real-time quantitative PCR, oligonucleotides were designed with the computer program Oligo 6 (MedProbe), imposing a melting temperature of 60°C and an amplicon length between 150 and 300 bp.…”

“…Real-time quantitative PCR was achieved as described in Ref. 16. Each sample was analyzed at least twice.…”

Les syncytines

“…Une recherche exhaustive de gènes d'enveloppe codants dans le génome humain n'a révélé que 18 protéines d'enveloppe putatives [6,7]. Parmi celles ayant potentiellement une fonction, citons la protéine ERV-3, d'expression placentaire et codée par un gène proviral présent chez les Hominoïdae et les singes de l'Ancien Monde [8].…”