Abstract
The naked mole-rat (Heterocephalus glaber) is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam), a tumour-associated protein. Also of interest are the protease inhibitor, alpha2-macroglobulin (A2m), and the mitochondrial complex II subunit Sdhc, both ageing-related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics.
Highlights
Understanding the mechanisms underlying the exceptional resistance to ageing processes and age-related diseases of long-lived species may lead to the discovery of senescence-retarding mechanisms [1]
We found genes associated with mitochondrial matrix (2.1E-6) and oxidation reduction (6.7E-6) enriched in our hits when using GO terms
Since a number of other rodents including mice, rats and guinea pigs already have had their genome sequenced, the naked mole-rat is a prime candidate for comparative genomics studies
Summary
Understanding the mechanisms underlying the exceptional resistance to ageing processes and age-related diseases of long-lived species may lead to the discovery of senescence-retarding mechanisms [1]. Heterocephalus belongs to the family Bathyergidae (African molerats) that includes 6 genera and possibly more than 50 other species They are distinct from laboratory mice and rats being part of the Hystricognath infraorder of rodents that includes the South American Caviomorphs (e.g. guinea pigs), and African Phiomorphs such as porcupines, rock rats and cane rats [2,3,4]. The naked mole-rat is the longest-lived rodent known with a lifespan of over 30 years [5] These animals appear to be cancer resistant since neither tumors nor lesions have been observed to date during necropsy [6], which is in marked contrast to mice since even longlived wild-derived animals of that species die primarily of neoplasia [7]. There is an immense interest in identifying the specific adaptations responsible for the unique traits of the naked mole-rat, and their longevity and cancer resistance
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