Transcriptome analysis of the response provided by Lasiopodomys mandarinus to severe hypoxia includes enhancing DNA repair and damage prevention

Abstract

Background: Severe hypoxia induces a series of stress responses in mammals; however, subterranean rodents have evolved several adaptation mechanisms of energy metabolisms and O 2 utilization for hypoxia. Mammalian brains show extreme aerobic metabolism. Following hypoxia exposure, mammals usually experience irreversible brain damage and can even develop serious diseases, such as hypoxic ischemic encephalopathy and brain edema. To investigate mechanisms underlying the responses of subterranean rodents to severe hypoxia, we performed a cross-species brain transcriptomic analysis using RNA sequencing and identified differentially expressed genes (DEGs) between the subterranean rodent Lasiopodomys mandarinus and its closely related aboveground species L. brandtii under severe hypoxia (5.0% O 2 , 6 h) and normoxia (20.9% O 2 , 6 h). Results: We obtained 361 million clean reads, including 69,611 unigenes in L. mandarinus and 69,360 in L. brandtii. We identified 359 and 515 DEGs by comparing the hypoxic and normoxia groups of L. mandarinus and L. brandtii, respectively. Gene Ontology (GO) analysis showed that upregulated DEGs in both species displayed similar terms in response to severe hypoxia; the main difference is that GO terms of L. brandtii were enriched in the immune system. However, in the downregulated DEGs, GO terms of L. mandarinus were enriched in cell proliferation and protein transport and those of L. brandtii were enriched in nuclease and hydrolase activities, particularly in terms of developmental functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that upregulated DEGs in L. mandarinus were associated with DNA repair and damage prevention as well as angiogenesis and metastasis inhibition, whereas downregulated DEGs were associated with neuronal synaptic transmission and tumor-associated metabolic pathways. In L. brandtii, upregulated KEGG pathways were enriched in the immune, endocrine, and cardiovascular systems and particularly in cancer-related pathways, whereas downregulated DEGs were associated with environmental information processing and misregulation in cancers.

Transcriptome analysis of the liver of Eospalax fontanierii under hypoxia

“…In our result cancer-related and immune genes for apoptotic and wound heal were up-regulated in hypoxia. Those results suggest cancer-related and hypoxia-related genes often shared and the cancer resistance trait in subterranean rodents such as blind mole rat and naked mole rat is related with the hypoxia tolerance (Dong et al, 2020). Although mechanisms of hypoxia adaption shared by different species with similar GO terms, the genes response to hypoxia found in our result may be different from that in other species, because the adaptation of subterranean rodents exhibits species specifity (Jiang et al, 2020).…”

Phylogeny and evolution ofLasiopodomysin subfamily Arvivolinae based on mitochondrial genomics

“…Environmental stress caused a major driving on evolutionary process ( Parsons, 2005 ). In the species of rodents, limited oxygen availability resulted in evolutionary adaptation and appearance of various strategies ( Pamenter et al, 2020 ), such as different colonial habitats of life—subterranean ( L. mandarinus ) and plateau ( L. fuscus ); these strategies formed unique physiological and molecular adaptations to hypoxia ( Jiang et al, 2020 ; Dong, Wang & Jiang, 2020 ). Our study supports a history of rapid population expansion under positive selection via mitogenome sequences such as the ATP6 gene, which uses oxygen to create adenosine triphosphate.…”

“…The differences in the environmental adaptability of proximal species are closely related to the historical events experienced during evolution, which play a key role in our understanding of the causes of current differences in life history among these species. However, the historical event that caused the Lasiopodomys species to adapt to a different environment has rarely been mentioned ( Dong et al, 2018 ; Dong, Wang & Jiang, 2020 ).…”

The mTORC1/eIF4E/HIF-1α Pathway Mediates Glycolysis to Support Brain Hypoxia Resistance in the Gansu Zokor, Eospalax cansus

“…Although mammals are largely intolerant of hypoxia and their brains exhibit exquisite sensitivity to hypoxia, a few species, such as subterranean rodents, inhabit hypoxic niches and are able to survive hypoxia ( Su et al, 2013 ; Nayak et al, 2016 ; Grimes et al, 2017 ; Altwasser et al, 2019 ; Li et al, 2019 ; Pamenter et al, 2019 ; Dong et al, 2020 ). These subterranean rodents have evolved various strategies to cope with the harsh environmental pressures of the hypoxic environment.…”

“…These subterranean rodents have evolved various strategies to cope with the harsh environmental pressures of the hypoxic environment. All six African mole-rat species have sufficient antioxidant capacity to respond to dynamic hypoxia ( Logan et al, 2020 ), Lasiopodomys mandarinus , Spalax ehrenbergi (the blind mole rat) and Heterocephalus glaber (the naked mole rat) all show hypoxia adaptation as an enhanced capacity for DNA repair and damage prevention ( Shams et al, 2013 ; Lewis et al, 2016 ; Dong et al, 2020 ). Eospalax fontanierii exhibits reduced blood circulation resistance under hypoxia, which has a protective effect of myocardial function ( Xu et al, 2019 ).…”