Mitochondrial DNA The Journal of DNA Mapping, Sequencing, and Analysis
ISSN: 1940-1736 (Print) 1940-1744 (Online) Journal homepage: http://www.tandfonline.com/loi/imdn20
Complete mitochondrial genome sequence and mutations of the cardiac hypertrophy model inbred rat strain (Muridae; Rattus) Rong Zhu, Zi-li Meng, Liang Chen, Wei Chen, Hong Wang & Yong-qing Hong To cite this article: Rong Zhu, Zi-li Meng, Liang Chen, Wei Chen, Hong Wang & Yong-qing Hong (2014): Complete mitochondrial genome sequence and mutations of the cardiac hypertrophy model inbred rat strain (Muridae; Rattus), Mitochondrial DNA To link to this article: http://dx.doi.org/10.3109/19401736.2014.936420
Published online: 11 Aug 2014.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=imdn20 Download by: [Deakin University Library]
Date: 05 November 2015, At: 15:07
http://informahealthcare.com/mdn ISSN: 1940-1736 (print), 1940-1744 (electronic) Mitochondrial DNA, Early Online: 1–2 ! 2014 Informa UK Ltd. DOI: 10.3109/19401736.2014.936420
MITOGENOME ANNOUNCEMENT
Complete mitochondrial genome sequence and mutations of the cardiac hypertrophy model inbred rat strain (Muridae; Rattus) Rong Zhu1, Zi-li Meng1, Liang Chen1, Wei Chen1, Hong Wang2, and Yong-qing Hong1 Department of Respiratory Medicine, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China and 2Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China
Downloaded by [Deakin University Library] at 15:07 05 November 2015
1
Abstract
Keywords
In the present work we undertook the complete mitochondrial genome sequencing of a important cardiac hypertrophy model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region (D-loop region). The mutation events were also reported.
Cardiac hypertrophy, genome, mitochondrion
Animals have been used by humans for centuries to understand their own biology. In cardiovascular research, animal models have allowed the study of cardiovascular disease in the early stages, as well as the investigation of the mechanisms of the pathogenesis of cardiovascular disease and the effects of drug intervention. Cardiac hypertrophy is an increase in the mass of the contractile and ancillary proteins of the heart above that which is normal for the given stage of its maturation growth (Shapiro & Sugden, 1996). Inbred rat and mouse strains with variations in their mitochondrial genomic sequences serve as good substrates for construction of conplastic strains for examining genetic contributions. Several complex traits are controlled by genetic elements of the mitochondrial genome (Chen et al., 2008; Gregorova et al., 2008). The SHR-F has been long known to have many similarities to human essential hypertension-induced heart failure (Doggrell & Brown, 1998; Pfeffer et al., 1979) including the important feature
History Received 12 June 2014 Accepted 15 June 2014 Published online 11 August 2014
that impaired myocardial performance is a late feature that precedes overt failure. In this study, complete mitochondrial genome of the cardiac hypertrophy model inbred rat strain SHRF108 was reported. The animal experiments were conducted as per pre-approved protocols by the Animal Care and Use Committee. DNA was extracted from tail biopsies using the Qiagen DNA Isolation kit (Hilden, Germany). Polymerase chain reaction (PCR) was carried out using 22 pairs of primers to amplify the entire mitochondrial genome. Mitochondrial DNA information of this strain was described in the Table 1 and sequence from the current study were deposited in GenBank (Accession No. KJ939361). The mitochondrial genome was 16,308 bp long including 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 1 control region. The total length of the protein-coding gene sequences was 11,437 bp. Most protein-coding genes initiated with ATG except for ND2, ND3 and ND5 which began with ATA. Eight protein-coding genes
Table 1. Genes encoded by this mitochondrial genome. Position Gene
From Phe
tRNA 12S rRNA tRNAVal 16S rRNA tRNALeu ND1 tRNAIle tRNAGln
362 432 1388 1455 3025 3102 4058 4124
Base composition (%) To 429 1386 1454 3024 3099 4058 4126 4195
Size (bp)
A
C
G
T
67 955 67 1570 75 957 69 72
35.8 36.8 38.8 37.7 33.3 31.9 40.6 25.0
25.4 22.7 19.4 21.0 21.3 27.9 13.0 9.7
17.9 18.0 11.9 17.7 16.0 12.6 14.5 29.2
20.9 22.5 29.9 23.6 29.4 27.6 31.9 36.1
Start codon
ATG
Stop codon
TAA
Strand H H H H H H H L
(continued )
Correspondence: Hong Wang, Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China. E-mail: [email protected] Yong-qing Hong, Department of Respiratory Medicine, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China. E-mail: [email protected]
2
R. Zhu et al.
Mitochondrial DNA, Early Online: 1–2
Table 1. Continued
Position Gene
Downloaded by [Deakin University Library] at 15:07 05 November 2015
Met
tRNA ND2 tRNATrp tRNAAla tRNAAsn OL tRNACys tRNATyr COX1 tRNASer tRNAAsp COX2 tRNALys ATP8 ATP6 COX3 tRNAGly ND3 tRNAArg ND4L ND4 tRNAHis tRNASer tRNALeu ND5 ND6 tRNAGlu CytB tRNAThr tRNAPro
Base composition (%)
From
To
Size (bp)
A
C
G
T
4198 4267 5309 5377 5447 5520 5552 5619 5688 7230 7306 7375 8065 8130 8291 8971 9755 9824 10,171 10,240 10,530 11,908 11,978 12,039 12,110 13,914 14,442 14,515 15,658 15,727
4266 5310 5375 5445 5519 5550 5618 5686 7232 7298 7373 8058 8127 8330 8971 9774 9823 10,180 10,239 10,536 11,907 11,977 12,037 12,109 13,930 14,441 14,510 15,654 15,727 15,789
69 1044 67 69 73 31 67 68 1545 69 68 684 63 201 681 804 69 357 69 297 1378 70 60 71 1821 528 69 1140 70 66
27.5 36.4 37.3 27.6 23.3 35.5 25.4 33.8 28.8 26.1 36.8 34.2 34.9 39.8 33.6 26.5 31.9 30.3 40.6 32.3 32.3 41.4 31.7 38.0 32.7 22.2 29.0 31.2 34.3 24.2
24.6 26.4 20.9 10.1 16.4 29.0 20.9 16.2 25.3 14.5 13.2 23.8 17.5 23.9 27.4 28.7 18.8 29.4 10.1 24.6 28.2 15.7 18.3 14.1 29.3 8.7 11.6 30.2 21.4 13.7
18.9 8.9 16.4 23.2 31.5 25.8 25.4 20.6 16.3 27.5 17.6 14.6 17.5 7.9 11.1 14.8 16.0 12.9 10.1 11.5 10.9 8.6 16.7 18.3 10.5 28.2 20.3 13.4 17.1 28.8
29.0 28.3 25.4 39.1 28.8 9.7 28.3 29.4 29.6 31.9 32.4 27.4 30.1 28.4 27.9 30.0 33.3 27.4 39.2 31.6 28.6 34.3 33.3 29.6 27.5 40.9 39.1 25.2 27.2 33.3
terminated with TAA whereas the ND2, ND3 and COX3 genes terminated with TAG and the CytB gene terminated with AGA. The incomplete stop codon (T– –) is used in ND4. A strong bias against G at the third codon position is observed in the proteincoding genes. The length of tRNA genes vary from 60 to 73 bp. Sequence data obtained from the current study were compared with the reference BN sequence (AC_000022.1). Eighty-nine variations in mtDNA were observed between these two strains. 35.5% of the variations were within gene-coding sequences, 18.7% were within non-coding RNA sequences, and 45.8% were synonymous variants.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Start codon
Stop codon
ATA
TAG
ATG
TAA
ATG
TAA
ATG ATG ATG
TAA TAA TAG
ATA
TAG
ATG ATG
TAA T– –
ATA ATG
TAA TAA
ATG
AGA
Strand H H H L L L L L H L H H H H H H H H H H H H H H H L L H H L
References Chen J, Lu Y, Lee CH, Li R, Leiter EH, Mathews CE. (2008) Commonalities of genetic resistance to spontaneous autoimmune and free radical-mediated diabetes. Free Radic Biol Med 45: 1263–70. Doggrell SA, Brown L. (1998). Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res 39:89–105. Gregorova S, Divina P, Storchova R, Trachtulec Z, Fotopulosova V, Svenson KL, Donahue LR, et al. (2008). Mouse consomic strains: Exploiting genetic divergence between Mus musculus and Mus domesticus subspecies. Genome Res 18:509–15. Pfeffer JM, Pfeffer MA, Fishbein MC, Frohlich ED. (1979). Cardiac function and morphology with aging in the spontaneously hypertensive rat. Am J Physiol 237:461–8. Shapiro LM, Sugden PH. (1996) Left ventricular hypertrophy. In: Julian DG, Camm AJ, Fox KM, Hall RTC, Poole-Wilson PA, editors. Diseases of the heart. 2nd ed. London: Saunders. p 23–39.
ISSN: 1940-1736 (Print) 1940-1744 (Online) Journal homepage: http://www.tandfonline.com/loi/imdn20
Complete mitochondrial genome sequence and mutations of the cardiac hypertrophy model inbred rat strain (Muridae; Rattus) Rong Zhu, Zi-li Meng, Liang Chen, Wei Chen, Hong Wang & Yong-qing Hong To cite this article: Rong Zhu, Zi-li Meng, Liang Chen, Wei Chen, Hong Wang & Yong-qing Hong (2014): Complete mitochondrial genome sequence and mutations of the cardiac hypertrophy model inbred rat strain (Muridae; Rattus), Mitochondrial DNA To link to this article: http://dx.doi.org/10.3109/19401736.2014.936420
Published online: 11 Aug 2014.
Submit your article to this journal
Article views: 21
View related articles
View Crossmark data
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=imdn20 Download by: [Deakin University Library]
Date: 05 November 2015, At: 15:07
http://informahealthcare.com/mdn ISSN: 1940-1736 (print), 1940-1744 (electronic) Mitochondrial DNA, Early Online: 1–2 ! 2014 Informa UK Ltd. DOI: 10.3109/19401736.2014.936420
MITOGENOME ANNOUNCEMENT
Complete mitochondrial genome sequence and mutations of the cardiac hypertrophy model inbred rat strain (Muridae; Rattus) Rong Zhu1, Zi-li Meng1, Liang Chen1, Wei Chen1, Hong Wang2, and Yong-qing Hong1 Department of Respiratory Medicine, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China and 2Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China
Downloaded by [Deakin University Library] at 15:07 05 November 2015
1
Abstract
Keywords
In the present work we undertook the complete mitochondrial genome sequencing of a important cardiac hypertrophy model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region (D-loop region). The mutation events were also reported.
Cardiac hypertrophy, genome, mitochondrion
Animals have been used by humans for centuries to understand their own biology. In cardiovascular research, animal models have allowed the study of cardiovascular disease in the early stages, as well as the investigation of the mechanisms of the pathogenesis of cardiovascular disease and the effects of drug intervention. Cardiac hypertrophy is an increase in the mass of the contractile and ancillary proteins of the heart above that which is normal for the given stage of its maturation growth (Shapiro & Sugden, 1996). Inbred rat and mouse strains with variations in their mitochondrial genomic sequences serve as good substrates for construction of conplastic strains for examining genetic contributions. Several complex traits are controlled by genetic elements of the mitochondrial genome (Chen et al., 2008; Gregorova et al., 2008). The SHR-F has been long known to have many similarities to human essential hypertension-induced heart failure (Doggrell & Brown, 1998; Pfeffer et al., 1979) including the important feature
History Received 12 June 2014 Accepted 15 June 2014 Published online 11 August 2014
that impaired myocardial performance is a late feature that precedes overt failure. In this study, complete mitochondrial genome of the cardiac hypertrophy model inbred rat strain SHRF108 was reported. The animal experiments were conducted as per pre-approved protocols by the Animal Care and Use Committee. DNA was extracted from tail biopsies using the Qiagen DNA Isolation kit (Hilden, Germany). Polymerase chain reaction (PCR) was carried out using 22 pairs of primers to amplify the entire mitochondrial genome. Mitochondrial DNA information of this strain was described in the Table 1 and sequence from the current study were deposited in GenBank (Accession No. KJ939361). The mitochondrial genome was 16,308 bp long including 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 1 control region. The total length of the protein-coding gene sequences was 11,437 bp. Most protein-coding genes initiated with ATG except for ND2, ND3 and ND5 which began with ATA. Eight protein-coding genes
Table 1. Genes encoded by this mitochondrial genome. Position Gene
From Phe
tRNA 12S rRNA tRNAVal 16S rRNA tRNALeu ND1 tRNAIle tRNAGln
362 432 1388 1455 3025 3102 4058 4124
Base composition (%) To 429 1386 1454 3024 3099 4058 4126 4195
Size (bp)
A
C
G
T
67 955 67 1570 75 957 69 72
35.8 36.8 38.8 37.7 33.3 31.9 40.6 25.0
25.4 22.7 19.4 21.0 21.3 27.9 13.0 9.7
17.9 18.0 11.9 17.7 16.0 12.6 14.5 29.2
20.9 22.5 29.9 23.6 29.4 27.6 31.9 36.1
Start codon
ATG
Stop codon
TAA
Strand H H H H H H H L
(continued )
Correspondence: Hong Wang, Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China. E-mail: [email protected] Yong-qing Hong, Department of Respiratory Medicine, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China. E-mail: [email protected]
2
R. Zhu et al.
Mitochondrial DNA, Early Online: 1–2
Table 1. Continued
Position Gene
Downloaded by [Deakin University Library] at 15:07 05 November 2015
Met
tRNA ND2 tRNATrp tRNAAla tRNAAsn OL tRNACys tRNATyr COX1 tRNASer tRNAAsp COX2 tRNALys ATP8 ATP6 COX3 tRNAGly ND3 tRNAArg ND4L ND4 tRNAHis tRNASer tRNALeu ND5 ND6 tRNAGlu CytB tRNAThr tRNAPro
Base composition (%)
From
To
Size (bp)
A
C
G
T
4198 4267 5309 5377 5447 5520 5552 5619 5688 7230 7306 7375 8065 8130 8291 8971 9755 9824 10,171 10,240 10,530 11,908 11,978 12,039 12,110 13,914 14,442 14,515 15,658 15,727
4266 5310 5375 5445 5519 5550 5618 5686 7232 7298 7373 8058 8127 8330 8971 9774 9823 10,180 10,239 10,536 11,907 11,977 12,037 12,109 13,930 14,441 14,510 15,654 15,727 15,789
69 1044 67 69 73 31 67 68 1545 69 68 684 63 201 681 804 69 357 69 297 1378 70 60 71 1821 528 69 1140 70 66
27.5 36.4 37.3 27.6 23.3 35.5 25.4 33.8 28.8 26.1 36.8 34.2 34.9 39.8 33.6 26.5 31.9 30.3 40.6 32.3 32.3 41.4 31.7 38.0 32.7 22.2 29.0 31.2 34.3 24.2
24.6 26.4 20.9 10.1 16.4 29.0 20.9 16.2 25.3 14.5 13.2 23.8 17.5 23.9 27.4 28.7 18.8 29.4 10.1 24.6 28.2 15.7 18.3 14.1 29.3 8.7 11.6 30.2 21.4 13.7
18.9 8.9 16.4 23.2 31.5 25.8 25.4 20.6 16.3 27.5 17.6 14.6 17.5 7.9 11.1 14.8 16.0 12.9 10.1 11.5 10.9 8.6 16.7 18.3 10.5 28.2 20.3 13.4 17.1 28.8
29.0 28.3 25.4 39.1 28.8 9.7 28.3 29.4 29.6 31.9 32.4 27.4 30.1 28.4 27.9 30.0 33.3 27.4 39.2 31.6 28.6 34.3 33.3 29.6 27.5 40.9 39.1 25.2 27.2 33.3
terminated with TAA whereas the ND2, ND3 and COX3 genes terminated with TAG and the CytB gene terminated with AGA. The incomplete stop codon (T– –) is used in ND4. A strong bias against G at the third codon position is observed in the proteincoding genes. The length of tRNA genes vary from 60 to 73 bp. Sequence data obtained from the current study were compared with the reference BN sequence (AC_000022.1). Eighty-nine variations in mtDNA were observed between these two strains. 35.5% of the variations were within gene-coding sequences, 18.7% were within non-coding RNA sequences, and 45.8% were synonymous variants.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Start codon
Stop codon
ATA
TAG
ATG
TAA
ATG
TAA
ATG ATG ATG
TAA TAA TAG
ATA
TAG
ATG ATG
TAA T– –
ATA ATG
TAA TAA
ATG
AGA
Strand H H H L L L L L H L H H H H H H H H H H H H H H H L L H H L
References Chen J, Lu Y, Lee CH, Li R, Leiter EH, Mathews CE. (2008) Commonalities of genetic resistance to spontaneous autoimmune and free radical-mediated diabetes. Free Radic Biol Med 45: 1263–70. Doggrell SA, Brown L. (1998). Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res 39:89–105. Gregorova S, Divina P, Storchova R, Trachtulec Z, Fotopulosova V, Svenson KL, Donahue LR, et al. (2008). Mouse consomic strains: Exploiting genetic divergence between Mus musculus and Mus domesticus subspecies. Genome Res 18:509–15. Pfeffer JM, Pfeffer MA, Fishbein MC, Frohlich ED. (1979). Cardiac function and morphology with aging in the spontaneously hypertensive rat. Am J Physiol 237:461–8. Shapiro LM, Sugden PH. (1996) Left ventricular hypertrophy. In: Julian DG, Camm AJ, Fox KM, Hall RTC, Poole-Wilson PA, editors. Diseases of the heart. 2nd ed. London: Saunders. p 23–39.
