http://informahealthcare.com/mdn ISSN: 1940-1736 (print), 1940-1744 (electronic) Mitochondrial DNA, Early Online: 1–2 ! 2015 Informa UK Ltd. DOI: 10.3109/19401736.2014.1003866
MITOGENOME ANNOUNCEMENT
Complete mitochondrial genome sequence and mutations of the lung carcinoma model inbred C57BL/6 mice strain Hanyu Jin*, Li Chang*, Ming Zhang, and Wenhui Li
Mitochondrial DNA Downloaded from informahealthcare.com by Fudan University on 05/11/15 For personal use only.
Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China Abstract
Keywords
In the present work, we undertook the complete mitochondrial genome sequencing of an important lung carcinoma model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one non-coding control region (D-loop region). The mutation events were also reported.
Genome, lung carcinoma, mitochondrion
Animals have been used by humans for centuries to understand their own biology. In lung carcinoma research, animal models have allowed the study of lung carcinoma disease in the early stages, as well as the investigation of the mechanisms of the pathogenesis of lung carcinoma disease and the effects of drug intervention (Kishi et al., 2014). Lung cancer is the most frequent cause of cancer-related deaths and causes over one million deaths worldwide each year. Despite significant strides in the diagnosis and treatment of lung cancer, the prognosis is extremely poor, with the overall 5-year survival rates still remaining around 15%. Lung cancer is the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) is the most common pathological type of lung cancer, divided into squamous cell carcinoma and adenocarcinoma. Despite better techniques of surgery and improvement in adjuvant and neoadjuvant therapy, the median survival of advanced NSCLC is only 8–10 months (Kim & Kim, 2015; Sun et al., 2015). Inbred rat and mouse strains with variations in their mitochondrial genomic sequences serve as good substrates for the construction of conplastic strains for examining genetic contributions. Several complex traits are
History Received 1 December 2014 Accepted 5 December 2014 Published online 20 January 2015
controlled by genetic elements of the mitochondrial genome (Chen et al., 2014). Here, we reported complete mitochondrial genome sequence of an lung carcinoma inbred C57BL/6 mice model. Total DNA was extracted from the lung tissue of a female individual that harbors a serious lung carcinoma. 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 was deposited in GenBank (accession no. KJ939361). The mitochondrial genome is 16,308 bp long including 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and one control region. The total length of the proteincoding gene sequences is 11,437 bp. Most protein-coding genes initiate with ATG except for ND2, ND3, and ND5 which begin with ATA. Eight protein-coding genes terminate with TAA whereas the ND2, ND3, and COX3 genes terminate with TAG and the CytB gene terminates 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 protein-coding genes. The length of
*These authors contribute equally to this work. Correspondence: Wenhui Li, PhD, Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, No. 519, Kunzhou Road, Kunming, China. E-mail: [email protected]
2
H. Jin 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 Fudan University on 05/11/15 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
362 432 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 15,727
429 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 15,789
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
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). About 89 variations in mtDNA were observed between these two strains. About 35.5% of the variations were within gene-coding sequences, 18.7% were within noncoding 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. This study was supported by the grants from National Natural Science Foundation of China (Nos. 30960439 and 81101693), National Key Clinical Specialty (Oncology) fund, and Yunnan National Natural Science Foundation (No. 2011FB206).
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
References Chen X-Z, Fang Y, Shi Y-H, Cui J-H, Li L-Y, Xu Y-C, Ling B. (2014). Mitochondrial D310 instability in Chinese lung cancer patients. Mitochondrial DNA, early online, DOI:10.3109/19401736.2014. 936426. Kim Y, Kim DH. (2015). CpG island hypermethylation as a biomarker for the early detection of lung cancer. Methods Mol Biol 1238:141–71. Kishi S, Yokohira M, Yamakawa K, Saoo K, Imaida K. (2014). Significance of the progesterone receptor and epidermal growth factor receptor, but not the estrogen receptor, in chemically induced lung carcinogenesis in female A/J mice. Oncol Lett 8:2379–86. Sun Z, Wang Z, Liu X, Wang D. (2015). New development of inhibitors targeting the PI3K/AKT/mTOR pathway in personalized treatment of non-small-cell lung cancer. Anticancer Drugs 26:1–14.
MITOGENOME ANNOUNCEMENT
Complete mitochondrial genome sequence and mutations of the lung carcinoma model inbred C57BL/6 mice strain Hanyu Jin*, Li Chang*, Ming Zhang, and Wenhui Li
Mitochondrial DNA Downloaded from informahealthcare.com by Fudan University on 05/11/15 For personal use only.
Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, China Abstract
Keywords
In the present work, we undertook the complete mitochondrial genome sequencing of an important lung carcinoma model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one non-coding control region (D-loop region). The mutation events were also reported.
Genome, lung carcinoma, mitochondrion
Animals have been used by humans for centuries to understand their own biology. In lung carcinoma research, animal models have allowed the study of lung carcinoma disease in the early stages, as well as the investigation of the mechanisms of the pathogenesis of lung carcinoma disease and the effects of drug intervention (Kishi et al., 2014). Lung cancer is the most frequent cause of cancer-related deaths and causes over one million deaths worldwide each year. Despite significant strides in the diagnosis and treatment of lung cancer, the prognosis is extremely poor, with the overall 5-year survival rates still remaining around 15%. Lung cancer is the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) is the most common pathological type of lung cancer, divided into squamous cell carcinoma and adenocarcinoma. Despite better techniques of surgery and improvement in adjuvant and neoadjuvant therapy, the median survival of advanced NSCLC is only 8–10 months (Kim & Kim, 2015; Sun et al., 2015). Inbred rat and mouse strains with variations in their mitochondrial genomic sequences serve as good substrates for the construction of conplastic strains for examining genetic contributions. Several complex traits are
History Received 1 December 2014 Accepted 5 December 2014 Published online 20 January 2015
controlled by genetic elements of the mitochondrial genome (Chen et al., 2014). Here, we reported complete mitochondrial genome sequence of an lung carcinoma inbred C57BL/6 mice model. Total DNA was extracted from the lung tissue of a female individual that harbors a serious lung carcinoma. 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 was deposited in GenBank (accession no. KJ939361). The mitochondrial genome is 16,308 bp long including 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and one control region. The total length of the proteincoding gene sequences is 11,437 bp. Most protein-coding genes initiate with ATG except for ND2, ND3, and ND5 which begin with ATA. Eight protein-coding genes terminate with TAA whereas the ND2, ND3, and COX3 genes terminate with TAG and the CytB gene terminates 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 protein-coding genes. The length of
*These authors contribute equally to this work. Correspondence: Wenhui Li, PhD, Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, No. 519, Kunzhou Road, Kunming, China. E-mail: [email protected]
2
H. Jin 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 Fudan University on 05/11/15 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
362 432 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 15,727
429 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 15,789
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
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). About 89 variations in mtDNA were observed between these two strains. About 35.5% of the variations were within gene-coding sequences, 18.7% were within noncoding 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. This study was supported by the grants from National Natural Science Foundation of China (Nos. 30960439 and 81101693), National Key Clinical Specialty (Oncology) fund, and Yunnan National Natural Science Foundation (No. 2011FB206).
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
References Chen X-Z, Fang Y, Shi Y-H, Cui J-H, Li L-Y, Xu Y-C, Ling B. (2014). Mitochondrial D310 instability in Chinese lung cancer patients. Mitochondrial DNA, early online, DOI:10.3109/19401736.2014. 936426. Kim Y, Kim DH. (2015). CpG island hypermethylation as a biomarker for the early detection of lung cancer. Methods Mol Biol 1238:141–71. Kishi S, Yokohira M, Yamakawa K, Saoo K, Imaida K. (2014). Significance of the progesterone receptor and epidermal growth factor receptor, but not the estrogen receptor, in chemically induced lung carcinogenesis in female A/J mice. Oncol Lett 8:2379–86. Sun Z, Wang Z, Liu X, Wang D. (2015). New development of inhibitors targeting the PI3K/AKT/mTOR pathway in personalized treatment of non-small-cell lung cancer. Anticancer Drugs 26:1–14.
