Scientists Crack the Damaraland Mole Rat Genome, Revealing Adaptations to a Subterranean Environment and Longevity

- The latest study was published online in Cell Reports -

Shenzhen —The latest study, led by scientists from Harvard Medical School, Ewha Womans University, BGI and other institutes, presents a high-quality Damaraland mole rat genome and reveals the genomic and transcriptomic events underlying the adaptations to subterranean environment and longevity. The latest study was published online today in Cell Reports.

African mole rats spend their lives in dark, unventilated environments that are rich in carbon dioxide and ammonia and low in oxygen. Naked mole rat (NMR) is the first African mole rat to be sequenced. To better understand the molecular mechanisms underlying the traits of African mole rats, the research team sequenced another African mole rat, theDamaraland mole rat (DMR), and improved the genome assembly of NMR.

They found 6,133 single-copy orthologous genes by comparing the sequences of DMR, NMR, rat, mouse, Chinese hamster, guinea pig, rabbit, dog, rhesus macaque and human, and constructed a phylogenetic tree. An interesting finding is that the DMR and NMR spited 26 Million years ago, which is similar to the time that between mouse and rat or between rhesus macaque and human.

The DMR and NMR live exclusively in the dark and display small eyes and poor visual acuity while advanced in the senses of smell and touch. This study revealed 212 and 378 gained gene families in DMR and NMR lineages, respectively, which are enriched in olfaction (sense of smell) genes that likely play an important role in social interaction and locating food in complete darkness. Meanwhile, there were 59 and 29 lost gene families found with tens of genes related to visual perception category.

When exploring the genetic mechanisms associated with the adaptations to subterranean environment, researchers found the arginase 1 (ARG1) has a radical residue change (His254 replaces Leu/Tyr) in both the NMR and DMR, which may improve ammonia removal efficiency. The transcriptomic analysis revealed several genes associated with DNA damage repair and responses to stress showed higher expression in subterranean rodents even during normoxia. This finding suggested that the improved DNA repair is an intrinsic mechanism of adaptation to an underground environment.

Subterranean rodents can live for as long as 20 to 30 years. In the study, researchers found two of six peroxiredoxins (PRDX2 and PRDX5) were expressed at lower levels in NMR and DMR livers, which combined with the reduced GPx1 activity may result in increased levels of reactive oxygen species (ROS) and suggests that the long-lived NMR and DMR can thrive despite elevated oxidative stress. The loss of Fas-activated serine/threonine kinase gene (FASTK) may help maintain neuronal integrity in long-lived mole rats, and keep their brains ‘‘younger’’. Reduced levels of insulin were observed in NMR and DMR, and a less bioactive insulin and altered downstream signaling may be associated with the longevity of African mole rats.

Zhiyong Huang, Project Manager from BGI, said, “The subterranean rodents are specialized species. The genome sequencing and comparison analysis of two mole rats can help us to understand the molecular mechanisms of subterranean rodents characteristics like longevity, hypoxia adaptation and cancer resistance. These findings also would benefit other biology and biomedical research.”

About BGI

BGI was founded in 1999 with the mission of being a premier scientific partner to the global research community. The goal of BGI is to make leading-edge genomic science highly accessible through its investment in infrastructure that leverages the best available technology, economies of scale, and expert bioinformatics resources. BGI, which includes both private non-profit genomic research institutes and sequencing application commercial units, and its affiliates, BGI Americas, headquartered in Cambridge, MA, and BGI Europe, headquartered in Copenhagen, Denmark, have established partnerships and collaborations with leading academic and government research institutions as well as global biotechnology and pharmaceutical companies, supporting a variety of disease, agricultural, environmental, and related applications.

BGI has established a proven track record of excellence, delivering results with high efficiency and accuracy for innovative, high-profile research which has generated over 250 publications in top-tier journals such as Nature and Science. These accomplishments include sequencing one percent of the human genome for the International Human Genome Project, contributing 10 percent to the International Human HapMap Project, carrying out research to combat SARS and German deadly E. coli, playing a key role in the Sino-British Chicken Genome Project, and completing the sequence of the rice genome, the silkworm genome, the first Asian diploid genome, the potato genome, and, most recently, have sequenced the human Gut metagenome, and a significant proportion of the genomes for 1,000 genomes.

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