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

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

On

e

hu

nd

red

fo

urt

een

th2nd grade

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

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 2

• 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

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 3

Analysis of PCR from human-rodent monochromosomal cell lines

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 4

10kb

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 5

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

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 6

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

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 7

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

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 8

Env Polymorphic Variants Are Functionally Preserved

5 mutation - 1 synonymous (VRSS)

4 nonsynonymous

(VRnS, VqnS, aRSS, VqSf)

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 9

Formation of syncytia by ERVWE1 envelopes

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 10

Comparison of the main features of the human ERVWE1 locus

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 11

Analysis of the ERVWE1 LTRs in hominoids

Ks/Ks = 0.8

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 12

Alignments of theenv translated region

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 13

Receptor-mediated fusion analysis

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 14

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

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 15

Research Article

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

Alignment of orthologous and paralogous env sequences

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 16

LQMV

Formation of syncytia by ERVWE1 envelopes

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 17

The sum of kimura distances

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 18

0.050

0.079

0.089

Local comparison of indel rate

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 19

None of these indels occurred within the env ORF

Phylogenetic analysis of the Ka/Ks ratio

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 20

Analysis of the Ka/Ks ratio along the env gene

On

e

hu

nd

red

fo

urt

een

th

MP

L

MP

L

M

PL

MP

L

M

PL

M

PL

www.primate.or.kr MPL I June 19 Saturday, 2004 I no. 114 I 21

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