http://informahealthcare.com/mdn ISSN: 1940-1736 (print), 1940-1744 (electronic) Mitochondrial DNA, Early Online: 1–2 ! 2014 Informa UK Ltd. DOI: 10.3109/19401736.2014.945546
MITOGENOME ANNOUNCEMENT
The complete mitochondrial genome sequence and mutations of the Lung cancer model inbred rat strain (Muridae; Rattus) Da-Ming Zhou1, Dan-Dan Zhu1, Qing-Feng Lu1, Wen-Bo Qiao2, and Yong-Zhi zhuang1 Department of Oncology Ward Two, Daqing Oil Field General Hospital, Daqing, People’s Republic of China and 2Department of Oncology, Cancer Hospital of Harbin, Harbin, People’s Republic of China
Mitochondrial DNA Downloaded from informahealthcare.com by Nyu Medical Center on 07/14/15 For personal use only.
1
Abstract
Keywords
We reported the complete mitochondrial genome sequencing of an important Lung cancer model inbred rat strain for the first time. The total length of the mitogenome was 16,312 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 noncoding control region. The mutation sites were analyzed by comparing with the reference BN strain.
Genome, lung cancer, mitochondrion
Lung cancer (also known as carcinoma of the lung) is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Several animal models have been developed in the last decades to better understand lung carcinogenesis, but most of these do not provide unambiguous information on the specific role of inflammation. Malkinson (2005) has studied a mouse model in which chronic inflammation, induced by butylated hydroxy toluene, promotes lung carcinogenesis previously initiated by a chemical carcinogen (methylcholanthrene). In the silica-induced rat lung carcinogenesis model, a single intratracheal instillation of crystalline silica dust suspended in saline leads to silicotic chronic inflammation and progressive proliferative epithelial lesions. Silica leads to the formation of silicotic granulomas, which consist of aggregates of activated macrophages that phagocytose dust mineral, induce collagen deposition, and recruit lymphoid cells. The rat silicotic granulomas remain stable or increase in size over time and, thus, are essentially irreversible. Very few animal models of cancer in which chronic inflammation drives carcinogenesis with no other carcinogenic insult have been molecularly characterized (Altomare et al., 2005; Bauer et al., 2005; Belinsky et al., 2002). In this study, the Fisher F344/Jcl female rats that derived from F344/Yit colony at Yakult Central Institute, and maintained in CLEA Japan Inc since 1982 (F344/Yit was introduced from
History Received 22 June 2014 Accepted 27 June 2014 Published online 12 November 2014
Charles River USA in 1971) were used for analyses. Genomic DNA was isolated from a F344/Jcl female and used as the template for PCR. Polymerase chain reaction (PCR) was carried out using 24 pairs of primers to amplify the entire mitochondrial genome. Mitochondrial DNA information of this strain was described in the Table 1. sequence from the current study were deposited in GenBank (Accession No. KM009112). The mitochondrial genome was 16,312 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 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–) was used in ND4. A strong bias against G at the third codon position was observed in the proteincoding genes. The length of tRNA genes varied from 60 to 75 bp. Sequence data obtained from the current study were compared with the reference BN sequence (AC_000022.1). Totally, 113 variations in mtDNA were observed between these two strains. Totally, 36.1% of the variations were within gene-coding sequences, 18.0% were within non-coding RNA sequences, and 45.9% were synonymous variants. No other genomic arrangement found between this two genomes.
Correspondence: Yong-Zhi Zhuang, Department of Oncology Ward Two, Daqing Oil Field General Hospital, Daqing, People0 s Republic of China. E-mail: [email protected]
2
D.-M. Zhou et al.
Mitochondrial DNA, Early Online: 1–2
Table 1. Genes encoded by this mitochondrial genome. Position Gene
Mitochondrial DNA Downloaded from informahealthcare.com by Nyu Medical Center on 07/14/15 For personal use only.
Phe
tRNA 12S rRNA tRNAVal 16S rRNA tRNALeu ND1 tRNAIle tRNAGln tRNAMet 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
360 432 1388 1455 3025 3102 4058 4124 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 15,731
427 1386 1454 3024 3099 4058 4126 4195 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 15,793
67 955 67 1570 75 957 69 72 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
35.8 36.8 38.8 37.7 33.3 31.9 40.6 25.0 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
25.4 22.7 19.4 21.0 21.3 27.9 13.0 9.7 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
17.9 18.0 11.9 17.7 16.0 12.6 14.5 29.2 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
20.9 22.5 29.9 23.6 29.4 27.6 31.9 36.1 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
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Altomare DA, Vaslet CA, Skele KL, De Rienzo A, Devarajan K, Jhanwar SC, McClatchey AI, et al. (2005). A mouse model recapitulating molecular features of human mesothelioma. Cancer Res 65:8090–5.
Start codon
Stop codon
ATG
TAA
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 H H H H L 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
Bauer AK, Dixon D, DeGraff LM, Cho HY, Walker CR, Malkinson AM, Kleeberger SR. (2005). Toll-like receptor 4 in butylated hydroxy toluene induced mouse pulmonary inflammation and tumorigenesis. J Natl Cancer Inst 97:1778–81. Belinsky SA, Snow SS, Nikula KJ, Finch GL, Tellez CS, Palmisano WA. (2002). Aberrant CpG island methylation of the p16 (INK4a) and estrogen receptor genes in rat lung tumors induced by particulate carcinogens. Carcinogenesis 23:335–9. Malkinson AM. (2005). Role of inflammation in mouse lung tumorigenesis: A review. Exp Lung Res 31:57–82.
MITOGENOME ANNOUNCEMENT
The complete mitochondrial genome sequence and mutations of the Lung cancer model inbred rat strain (Muridae; Rattus) Da-Ming Zhou1, Dan-Dan Zhu1, Qing-Feng Lu1, Wen-Bo Qiao2, and Yong-Zhi zhuang1 Department of Oncology Ward Two, Daqing Oil Field General Hospital, Daqing, People’s Republic of China and 2Department of Oncology, Cancer Hospital of Harbin, Harbin, People’s Republic of China
Mitochondrial DNA Downloaded from informahealthcare.com by Nyu Medical Center on 07/14/15 For personal use only.
1
Abstract
Keywords
We reported the complete mitochondrial genome sequencing of an important Lung cancer model inbred rat strain for the first time. The total length of the mitogenome was 16,312 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 noncoding control region. The mutation sites were analyzed by comparing with the reference BN strain.
Genome, lung cancer, mitochondrion
Lung cancer (also known as carcinoma of the lung) is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Several animal models have been developed in the last decades to better understand lung carcinogenesis, but most of these do not provide unambiguous information on the specific role of inflammation. Malkinson (2005) has studied a mouse model in which chronic inflammation, induced by butylated hydroxy toluene, promotes lung carcinogenesis previously initiated by a chemical carcinogen (methylcholanthrene). In the silica-induced rat lung carcinogenesis model, a single intratracheal instillation of crystalline silica dust suspended in saline leads to silicotic chronic inflammation and progressive proliferative epithelial lesions. Silica leads to the formation of silicotic granulomas, which consist of aggregates of activated macrophages that phagocytose dust mineral, induce collagen deposition, and recruit lymphoid cells. The rat silicotic granulomas remain stable or increase in size over time and, thus, are essentially irreversible. Very few animal models of cancer in which chronic inflammation drives carcinogenesis with no other carcinogenic insult have been molecularly characterized (Altomare et al., 2005; Bauer et al., 2005; Belinsky et al., 2002). In this study, the Fisher F344/Jcl female rats that derived from F344/Yit colony at Yakult Central Institute, and maintained in CLEA Japan Inc since 1982 (F344/Yit was introduced from
History Received 22 June 2014 Accepted 27 June 2014 Published online 12 November 2014
Charles River USA in 1971) were used for analyses. Genomic DNA was isolated from a F344/Jcl female and used as the template for PCR. Polymerase chain reaction (PCR) was carried out using 24 pairs of primers to amplify the entire mitochondrial genome. Mitochondrial DNA information of this strain was described in the Table 1. sequence from the current study were deposited in GenBank (Accession No. KM009112). The mitochondrial genome was 16,312 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 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–) was used in ND4. A strong bias against G at the third codon position was observed in the proteincoding genes. The length of tRNA genes varied from 60 to 75 bp. Sequence data obtained from the current study were compared with the reference BN sequence (AC_000022.1). Totally, 113 variations in mtDNA were observed between these two strains. Totally, 36.1% of the variations were within gene-coding sequences, 18.0% were within non-coding RNA sequences, and 45.9% were synonymous variants. No other genomic arrangement found between this two genomes.
Correspondence: Yong-Zhi Zhuang, Department of Oncology Ward Two, Daqing Oil Field General Hospital, Daqing, People0 s Republic of China. E-mail: [email protected]
2
D.-M. Zhou et al.
Mitochondrial DNA, Early Online: 1–2
Table 1. Genes encoded by this mitochondrial genome. Position Gene
Mitochondrial DNA Downloaded from informahealthcare.com by Nyu Medical Center on 07/14/15 For personal use only.
Phe
tRNA 12S rRNA tRNAVal 16S rRNA tRNALeu ND1 tRNAIle tRNAGln tRNAMet 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
360 432 1388 1455 3025 3102 4058 4124 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 15,731
427 1386 1454 3024 3099 4058 4126 4195 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 15,793
67 955 67 1570 75 957 69 72 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
35.8 36.8 38.8 37.7 33.3 31.9 40.6 25.0 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
25.4 22.7 19.4 21.0 21.3 27.9 13.0 9.7 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
17.9 18.0 11.9 17.7 16.0 12.6 14.5 29.2 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
20.9 22.5 29.9 23.6 29.4 27.6 31.9 36.1 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
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Altomare DA, Vaslet CA, Skele KL, De Rienzo A, Devarajan K, Jhanwar SC, McClatchey AI, et al. (2005). A mouse model recapitulating molecular features of human mesothelioma. Cancer Res 65:8090–5.
Start codon
Stop codon
ATG
TAA
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 H H H H L 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
Bauer AK, Dixon D, DeGraff LM, Cho HY, Walker CR, Malkinson AM, Kleeberger SR. (2005). Toll-like receptor 4 in butylated hydroxy toluene induced mouse pulmonary inflammation and tumorigenesis. J Natl Cancer Inst 97:1778–81. Belinsky SA, Snow SS, Nikula KJ, Finch GL, Tellez CS, Palmisano WA. (2002). Aberrant CpG island methylation of the p16 (INK4a) and estrogen receptor genes in rat lung tumors induced by particulate carcinogens. Carcinogenesis 23:335–9. Malkinson AM. (2005). Role of inflammation in mouse lung tumorigenesis: A review. Exp Lung Res 31:57–82.
