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Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human.

ABSTRACT: Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long-lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR.

SUBMITTER: MacRae SL

PROVIDER: S-EPMC4364841 | biostudies-other | 2015 Apr

REPOSITORIES: biostudies-other

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Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human.

MacRae Sheila L SL Zhang Quanwei Q Lemetre Christophe C Seim Inge I Calder Robert B RB Hoeijmakers Jan J Suh Yousin Y Gladyshev Vadim N VN Seluanov Andrei A Gorbunova Vera V Vijg Jan J Zhang Zhengdong D ZD

Aging cell 20150128 2

Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telom ...[more]

PMID: 25645816

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Project description:BACKGROUND: The naked mole rats (NMRs) are small-sized underground rodents with plenty of unusual traits. Their life expectancy can be up to thirty years, more than seven times longer than laboratory rat. Furthermore, they are resistant to both congenital and experimentally induced cancer genesis. These peculiar physiological and pathological characteristics allow them to become a suitable model for cancer and aging research. RESULTS: In this paper, we carried out a genome-wide comparative analysis of rat and NMR using the recently published genome sequence of NMR. First, we identified all the rat-NMR orthologous genes and specific genes within each of them. The expanded and contracted numbers of protein families in NMR were also analyzed when compared to rat. Seven cancer-related protein families appeared to be significantly expanded, whereas several receptor families were found to be contracted in NMR. We then chose those rat genes that were inexistent in NMR and adopted KEGG pathway database to investigate the metabolic processes in which their proteins may be involved. These genes were significantly enriched in two rat cancer pathways, "Pathway in cancer" and "Bladder cancer". In the rat "Pathway in cancer", 9 out of 14 paths leading to evading apoptosis appeared to be affected in NMR. In addition, a significant number of other NMR-missing genes enriched in several cancer-related pathways have been known to be related to a variety of cancers, implying that many of them may be also related to tumorigenesis in mammals. Finally, investigation of sequence variations among orthologous proteins between rat and NMR revealed that significant fragment insertions/deletions within important functional domains were present in some NMR proteins, which might lead to expressional and/or functional changes of these genes in different species. CONCLUSIONS: Overall, this study provides insights into understanding the possible anti-cancer mechanisms of NMR as well as searching for new cancer-related candidate genes.

Dataset Information

Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human.

Publications

Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human.

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