Evolutionary diversification of DYX1C1 gene transcripts by HERV-H LTR integration event Results &...
1
Evolutionary diversification of DYX1C1 gene Evolutionary diversification of DYX1C1 gene transcripts by HERV-H LTR integration event transcripts by HERV-H LTR integration event Results & Discussion Abstract DYX1C1 (dyslexia susceptibility 1 candidate 1) gene on human chromosome 15q21.3 is a candidate gene for de velopmental dyslexia. The DYX1C1 shows three alternati vely spliced transcripts in GenBank database. We found that one of transcripts is related to HERV-H LTR eleme nt that could affect the protein-coding region. The HE RV-H LTR element on human DYX1C1 gene seems to have be en integrated into our common ancestor genome after th e divergence of Old World monkeys and New World monkey s. RT-PCR analysis of HERV-H LTR-related transcript sh ows that five different alternative transcripts are ex pressed in several human tissues. Five different alter native splicing forms are also identified in various r hesus monkey tissues. From the sequencing analysis of various primate DNA samples, we found the lineage spec ific tandem repeated sequences of Old World monkeys in protein coding region. However, the formation of tande m repeated sequences did not affect the amino acid seq uences. Taken together, integration event of the HERV- H LTR element contributed to the DYX1C1 gene diversifi cation by affecting protein coding region during the p rimate evolution.………………………………………………………………………..… Yun-Ji Kim 1 , Jae-Won Huh 1 , Dae-Soo Kim 2 , Hong-Seok Ha 1 , Kung Ahn 1 , Ja-Rang Lee 1 , Min-In Bae 1 , and Heui-Soo Kim 1, 2 1 Division of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of K orea 2 PBBRC, Interdisciplinary Research Program of Bioinformatics, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea http://www.primate.or.kr Materials & Methods Plasmid DNA Isolation Transformation-Inoculation Ligation Electrophoresis-Gel purification Polymerase Chain Reaction (PCR) Gene Cloning Genomic DNAs & cDNA PCR & RT-PCR Bioinformatics QIAEX II gel extraction kit(Qia gen) High Pure plasmid isolation kit Human Monkey NCBI,BLAST,MEGA3 Introduction Chr.15 q21.3 NM_001033560.1 10 EXON1 2 3 4 5 6 7 8 9 EXON1 2 3 4 5 6 7 8 9 EXON1 2 3 4 5 6 7 8 9 NM_001033559.1 NM_13081.2 EXON1 2 3 4 5 6 7 8 9 EXON1 2 3 4 5 6 7 8 9 EXON1 2 3 4 5 6 7 9 NEW TRANSCRIPTS EXON1 2 3 4 5 6 7 9 V1 V1-1 V2 V3 V1-2 V1-3 V1-4 7’ 8’ 8’ S AS S AS M HU CH GO OR GI JM RH NM SQ CM 799 bp 1.Sin HS, Huh JW, Kim DS, Kang DW, Min DS, Kim TH, Ha HS, Kim HH, Lee SY, Kim HS. (2006) Transcriptional control of the HERV-H LTR element of the G SDML gene in human tissues and cancer cells. Arch Virol. 151(10):1985-94. 2. Okahara G, Matsubara S, Oda T, Sugimoto J, Jinno Y, Kanaya F. (2004) Expression analyses of human endogenous retroviruses (HERVs): tissue-specif ic and developmental stage-dependent expression of HERVs. Genomics. 84(6):982-90 References V1 V1-3 V1-4 V1- 1,V1-2 GAPDH 120 bp GAPDH 120 bp V3 V2 Number 1 2 3 4 5 6 7 8 Tissues adrenal gland cerebellum heart kidney liver lung testis trachea Human Intergation Time LTR in CDS 0.01 71 96 42 10 0 56 DYX1C1 HU DYX1C1 CH DYX1C1 GO DYX1C1 GI 10 0 DYX1C1 JM DYX1C1 RH DYX1C1 CM DYX1C1 SQ DYX1C1 NM LTR7 M 1 2 3 4 5 6 7 8 M 1 2 3 4 5 6 7 8 GAPDH 120 bp V1 V1-3 V1-4 V1- 1,V1-2 GAPDH 120 bp V3 V2 Model for DYX1C1 gene evolution Rhesus Coding region Untranslated regi on LTR7 M 1 2 3 4 5 6 7 8 M 1 2 3 4 5 6 7 8 Retroelement Retroposon SINE Retrotransposon LINE RNA intermediate - LTR element + LTR element - env + env - RT + RT Yeast Ty1/copia/truncated HERVs LTR ORF1 ORF2 LTR LTR LTR Human THE1 P Poly(A) Human Alu ORF1 ORF2 P Poly(A) L1 Retrovirus gag pol env LTR LTR Full-length HERVs/exogenous retrovirus Human Common ancesto r Rodent s ancest or Primat e ancest or Mous e Ra t New World monkey Old World monkey LTR 7 PB1D9 B1F Tandem duplication
-
Upload
samantha-roberts -
Category
Documents
-
view
213 -
download
0
Transcript of Evolutionary diversification of DYX1C1 gene transcripts by HERV-H LTR integration event Results &...
Evolutionary diversification of DYX1C1 gene Evolutionary diversification of DYX1C1 gene transcripts by HERV-H LTR integration eventtranscripts by HERV-H LTR integration event
Results & Discussion
Abstract
DYX1C1 (dyslexia susceptibility 1 candidate 1) gene on human chromosome 15q21.3 is a candidate gene for developmental dyslexia. The DYX1C1 shows three alternatively spliced transcripts in GenBank database. We found that one of transcripts is related to HERV-H LTR element that could affect the protein-coding region. The HERV-H LTR element on human DYX1C1 gene seems to have been integrated into our common ancestor genome after the divergence of Old World monkeys and New World monkeys. RT-PCR analysis of HERV-H LTR-related transcript shows that five different alternative transcripts are expressed in several human tissues. Five different alternative splicing forms are also identified in various rhesus monkey tissues. From the sequencing analysis of various primate DNA samples, we found the lineage specific tandem repeated sequences of Old World monkeys in protein coding region. However, the formation of tandem repeated sequences did not affect the amino acid sequences. Taken together, integration event of the HERV-H LTR element contributed to the DYX1C1 gene diversification by affecting protein coding region during the primateevolution.………………………………………………………………………..…
Yun-Ji Kim1, Jae-Won Huh1, Dae-Soo Kim2, Hong-Seok Ha1, Kung Ahn1, Ja-Rang Lee1, Min-In Bae1, and Heui-Soo Kim1, 2
1Division of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea2 PBBRC, Interdisciplinary Research Program of Bioinformatics, College of Natural Sciences, Pusan National University,
Busan 609-735, Republic of Korea
http://www.primate.or.kr
Materials & Methods
Plasmid DNA Isolation
Transformation-Inoculation
Ligation
Electrophoresis-Gel purification
Polymerase Chain Reaction (PCR)
Gene Cloning
Genomic DNAs& cDNA
PCR & RT-PCR
Bioinformatics
QIAEX II gel extraction kit(Qiagen)High Pure plasmid isolation kit
Human Monkey
NCBI,BLAST,MEGA3
Introduction
Chr.15
q21.3
NM_001033560.1
10
EXON1
2 3 4 5 6 7 8 9
EXON1 2 3 4 5 6 7 8 9
EXON1 2 3 4 5 6 7 8 9
NM_001033559.1
NM_13081.2
EXON1
2 3 4 5 6 7 8 9
EXON1
2 3 4 5 6 7 8 9
EXON1
2 3 4 5 6 7 9
NEW
TR
AN
SC
RIP
TS
EXON1
2 3 4 5 6 7 9
V1
V1-1
V2
V3
V1-2
V1-3
V1-4
7’
8’
8’
S AS
S AS
M HU CH GO OR GI JM RH NM SQ CM
799 bp
1. Sin HS, Huh JW, Kim DS, Kang DW, Min DS, Kim TH, Ha HS, Kim HH, Lee SY, Kim HS. (2006) Transcriptional control of the HERV-H LTR element of the GSDML gene in human tissues and cancer cells. Arch Virol. 151(10):1985-94.
2. Okahara G, Matsubara S, Oda T, Sugimoto J, Jinno Y, Kanaya F. (2004) Expression analyses of human endogenous retroviruses (HERVs): tissue-specific and developmental stage-dependent expression of HERVs. Genomics. 84(6):982-90
References
V1
V1-3
V1-4
V1-1,V1-2
GAPDH 120 bp
GAPDH 120 bp
V3
V2
Number 1 2 3 4 5 6 7 8
Tissues adrenal gland cerebellum heart kidney liver lung testis trachea
Hu
man
Inte
rgat
ion
Tim
e
LTR in CDS
0.01
7196
42
100 56
DYX1C1 HUDYX1C1 CH
DYX1C1 GODYX1C1 GI
100
DYX1C1 JMDYX1C1 RH
DYX1C1 CM
DYX1C1 SQDYX1C1 NM
LTR7
M 1 2 3 4 5 6 7 8 M 1 2 3 4 5 6 7 8
GAPDH 120 bp
V1
V1-3
V1-4
V1-1,V1-2
GAPDH 120 bp
V3
V2
Mod
el f
or D
YX
1C1
gen
e ev
olu
tion
Rh
esu
s
Coding region Untranslated regionLTR7
M 1 2 3 4 5 6 7 8 M 1 2 3 4 5 6 7 8
Retroelement
Retroposon
SINE
Retrotransposon
LINE
RNA intermediate
- LTR element + LTR element
- env + env
- RT + RT
Yeast Ty1/copia/truncated HERVsLTR ORF1 ORF2 LTR
LTR LTR
Human THE1
PPoly(A)
Human Alu
ORF1 ORF2PPoly(A)L1
Retrovirusgag pol envLTR LTR
Full-length HERVs/exogenous retrovirus
Human
Common ancestor
Rodents ancestor
Primate ancestor
Mouse RatNew World
monkeyOld World
monkey
LTR 7
PB1D9
B1F
Tandem duplication
