The endogenous retroviral locus The endogenous retroviral locus ERVWE1 is a bona fide gene involved ERVWE1 is a bona fide gene involved in hominoid placental physiology in hominoid placental physiology MPL MPL MPL MPL MPL MPL One hundred fourteenth 2 nd grade Park Eun Sil MPL I June 19 Saturday, 2004 I no. 114 I 1-
MPL MPL MPL MPL MPL MPL. The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology. One hundred fourteenth. 2 nd grade Park Eun Sil. MPL I June 19 Saturday , 2004 I no. 114 I 1-. - PowerPoint PPT Presentation
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
The endogenous retroviral locus The endogenous retroviral locus ERVWE1 is a bona fide gene involved in ERVWE1 is a bona fide gene involved in
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