Genome sequencing reveals insights into physiology and longevity of the naked mole rat

Abstract

The naked mole rat (NMR, Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal1. Although the size of a mouse, its maximum lifespan exceeds 30 years and makes this animal the longest living rodent. NMRs show negligible senescence, no age-related increase in mortality, and high fecundity until death2. In addition to delayed aging, NMRs are resistant to both spontaneous cancer and experimentally induced tumorigenesis3,4. NMRs pose a challenge to the theories that link aging, cancer and redox homeostasis. Although characterized by significant oxidative stress5, the NMR proteome does not show age-related susceptibility to oxidative damage nor increased ubiquitination6. NMRs naturally reside in large colonies with a single breeding female, the “queen,” who suppresses the sexual maturity of her subordinates11. NMRs also live in full darkness, at low oxygen and high carbon dioxide concentrations7, and are unable to sustain thermogenesis8 nor feel certain types of pain9,10. Here we report sequencing and analysis of the NMR genome, which revealed unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness, altered visual function, circadian rhythms and taste sensing, and insensitivity to low oxygen. This information provides insights into NMR’s exceptional longevity and capabilities to live in hostile conditions, in the dark and at low oxygen. The extreme traits of NMR, together with the reported genome and transcriptome information, offer unprecedented opportunities for understanding aging and advancing many other areas of biological and biomedical research.

Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity

“…POLB, involved in DNA maintenance, replication, and recombination, was among the top 1% hits at the 0.2 threshold but with a modest score of 3.3. Interestingly, three proteins among our hits were also recently reported to be under positive selection in the long-lived naked mole rat: COL3A1, PRKD2, and GSTO1 (Kim et al 2011). Fig.…”

“…CAPNS1, scoring 4.0 (rank 7; moderate), belongs to a well-conserved family of calcium-dependent, cysteine proteases whose link to cellular senescence and DNA damage response has been studied (Demarchi and Schneider 2007). COL3A1 (rank 4; relaxed) is a collagen-type protein whose expression is downregulated with age across tissues (de Magalhães et al 2009b) and has also been reported to be under positive selection in the long-lived naked mole rat (Kim et al 2011), making it a top candidate for selection in longlived lineages. Also, TAOK3 (rank 7; relaxed) is a serine/threonine-protein kinase whose overexpression may activate ERK1/ERK2 and JNK/SAPK (Zhang et al 2000).…”

Sequencing of allotetraploid cotton (Gossypium hirsutum L. acc. TM-1) provides a resource for fiber improvement

“…We obtained a 31-nucleotide depth distribution and observed that the peak depth was at 70. The following formula 48 was applied: genome size = total_kmer_ num/kmer_depth, where total_kmer_num is the total number of K-mers in the sequence, and kmer_depth is the peak depth on the K-mer frequency distribution map. Using this method, the size of the G. hirsutum genome is estimated to be 2.5 Gb.…”

Genome of the Chinese tree shrew

“…We used TreeFam 7.0 (http://www.treefam.org/) to define gene families among 15 mammalian genomes: human, chimpanzee, gorilla, orangutan, rhesus macaque, marmoset, Chinese tree shrew, northern tree shrew, rabbit, mouse, rat, dog, cow, opossum and platypus. We carried out the same pipeline and parameters used in our previously published study 58 . We obtained 18,823 gene families and 2,117 single-copy orthologues.…”