mpl mpl mpl mpl mpl mpl

The endogenous retroviral locus The endogenous retroviral locus ERVWE1 is a bona fide gene involved in ERVWE1 is a bona fide gene involved in

hominoid placental physiologyhominoid placental physiology

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Park Eun SilMPL I June 19 Saturday, 2004 I no. 114 I 1-

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• HERV elements were found to - multiple sclerosis (Perron et al., 1997) - schizophrenia (Karlsson et al., 2001) - testis (Mi et al., 2000) - placenta (Blond et al., 1999)• Intact HERV-W on chromosome 7q21, 7q22 have 100% identity to SYNCYTIN gene• ERVWE1 was shown to be the unique copy of the whole family having retained a complete env ORF

HERV-W env & syncytinHERV-W env & syncytin

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Analysis of PCR from human-rodent monochromosomal cell lines

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10kb

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Global sequencing strategy of the ERVWE1 locus

Few polymorphic

4 Full-length provirus : ~0.05%48 partial sequence : from 0.005% to 0.2% for the 5 LTRs and the 3 LTRs, respectively, 0.04% for the env ORF

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Analysis of the ERVWE1 LTRs in the human population(1)

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Analysis of the ERVWE1 LTRs in the human population(2)

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Env Polymorphic Variants Are Functionally Preserved

5 mutation - 1 synonymous (VRSS)

4 nonsynonymous

(VRnS, VqnS, aRSS, VqSf)

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Formation of syncytia by ERVWE1 envelopes

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Comparison of the main features of the human ERVWE1 locus

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Analysis of the ERVWE1 LTRs in hominoids

Ks/Ks = 0.8

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Alignments of theenv translated region

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Receptor-mediated fusion analysis

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DiscussionAge – 1. Retrotransposed at 15~20myr

2. fixed in the hominoid, degenerated in the OWM

ERVWE1 locus has tissue specificity

5 HERVWE1 LTR was the most active promoter in BeWo cells.

This recently acquired gene has become a bona fide gene.

Because the majority of the Eutherians do not contain the young ERVWE1 locus, it will be challenging to ascertain whether this retroviral acquisition represents an additionaladaptive or substitutive mechanism for placental morphogenesis

Evidence of selection on the domesticated ERVWE1 env retroviral element involved in plasc

entation

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Research Article

Bertrand Bonnaud*, Olivier Bouton*, Guy Oriol*, Valerie Cheynet*, Laurent Duret+ and Francois Mallet*

Alignment of orthologous and paralogous env sequences

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LQMV

Formation of syncytia by ERVWE1 envelopes

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The sum of kimura distances

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0.050

0.079

0.089

Local comparison of indel rate

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None of these indels occurred within the env ORF

Phylogenetic analysis of the Ka/Ks ratio

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Analysis of the Ka/Ks ratio along the env gene

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0.8 = neutral 0.8 = neutral evolutionevolution

1.2 = positive 1.2 = positive selectionselection

0.56 = purifying 0.56 = purifying selectionselection

ERVWE1 env has been subject to the action of natural selection