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

Sheila L Macrae,Robert B Calder,Jan Hoeijmakers,Andrei Seluanov,Vadim N Gladyshev,Christophe Lemetre,Jan Vijg,Zhengdong D Zhang,Quanwei Zhang,Inge Seim,Yousin Suh,Vera Gorbunova

doi:10.1111/acel.12314

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.

Highlights

While no orthologous sequences were found in the mouse genome, we identified an ortholog of the human replication protein A4 (RPA4) sequence in the naked mole rat (NMR) genome (Fig. S4)
While limitations in genome assemblies of most other species essentially constrained complete analysis, we did check the genomes of the guinea pig, chimpanzee, and rat for copy number variation in the four Genome maintenance (GM) genes identified with copy number variation between human, mouse, and NMR
We found that the number of nucleotide substitutions per site (K) in GM genes is on average 1.3 times higher between human and mouse than between human and NMR (Fig. 1A and Fig. S1A)

Summary

Introduction

We performed a comparative analysis of GM genes in the NMR, mouse, and human genomes. While we found evidence of gene expansion and many putative pseudogenes, there were only two genes, CCAAT/enhancer binding protein-c (CEBPG), and TERF1-interacting nuclear factor 2 (TINF2), with higher copy number in the NMR (Table 1, Fig. S4).

Results

Conclusion