Evolutionary impacts of purine metabolism genes on mammalian oxidative stress adaptation

Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabolism is an essential response to oxidative stress, and an imbalance between purine salvage and de novo biosynthesis pathways can generate damaging reactive oxygen species(ROS). Here, we examined the evolution of 117 purine metabolism-related genes to explore the accompanying molecular mechanisms of enhanced purine metabolism in mammals under high oxidative stress. We found that positively selected genes,convergent changes, and nonparallel amino acid substitutions are possibly associated with adaptation to oxidative stress in mammals. In particular, the evolution of convergent genes with c AMP and c GMP regulation roles may protect mammals from oxidative damage. Additionally, 32 genes were identified as under positive selection in cetaceans, including key purine salvage enzymes(i.e., HPRT1), suggesting improved re-utilization of non-recyclable purines avoid hypoxanthine accumulation and reduce oxidative stress. Most intriguingly, we found that six unique substitutions in cetacean xanthine dehydrogenase(XDH), an enzyme that regulates the generation of the ROS precursor xanthine oxidase(XO) during ischemic/hypoxic conditions, show enhanced enzyme activity and thermal stability and diminished XO conversion activity. These functional adaptations are likely beneficial for cetaceans by reducing radical oxygen species production during diving. In summary, our findings offer insights into the molecular and functional evolution of purine metabolism genes in mammalian oxidative stress adaptations.

High-quality chromosome-level genome assembly of the melon-headed whale(Peponocephala electra)

DEAR EDITOR,The melon-headed whale(Peponocephala electra),a small toothed whale in the Delphinidae family,inhabits tropical and subtropical oceans.It is an attractive model species for studying secondary aquatic adaptation and evolution.Here,we successfully assembled a high-quality chromosome-level genome of P.electra using Pac Bio and Hi-C sequencing technologies.

A chromosome-level genome of electric catfish(Malapterurus electricus)provided new insights into order Siluriformes evolution

The electric catfish(Malapterurus electricus),belonging to the family Malapteruridae,order Siluriformes(Actinopterygii:Ostariophysi),is one of the six branches that has independently evolved electrical organs.We assembled a 796.75 Mb M.electricus genome and anchored 88.72%sequences into 28 chromosomes.Gene family analysis revealed 295 expanded gene families that were enriched on functions related to glutamate receptors.Convergent evolutionary analyses of electric organs among different lineage of electric fishes further revealed that the coding gene of rho guanine nucleotide exchange factor 4-like(arhgef4),which is associated with G-protein coupled receptor(GPCR)signaling pathway,underwent adaptive parallel evolution.Gene identification suggests visual degradation in catfishes,and an important role for taste in environmental adaptation.Our findings fill in the genomic data for a branch of electric fish and provide a relevant genetic basis for the adaptive evolution of Siluriformes.

Oxidative stress drives divergent evolution of the glutathione peroxidase(GPX)gene family in mammals

The molecular basis for adaptations to extreme environments can now be understood by interrogating the everincreasing number of sequenced genomes.Mammals such as cetaceans,bats,and highland species can protect themselves from oxidative stress,a disruption in the balance of reactive oxygen species,which results in oxidative injury and cell damage.Here,we consider the evolution of the glutathione peroxidase(GPX)family of antioxidant enzymes by interrogating publicly available genome data from 70 mammalian species from all major clades.We identified 8 GPX subclasses ubiquitous to all mammalian groups.Mammalian GPX gene families resolved into the GPX4/7/8 and GPX1/2/3/5/6 groups and are characterized by several instances of gene duplication and loss,indicating a dynamic process of gene birth and death in mammals.Seven of the eight GPX subfamilies(all but GPX7)were under positive selection,with the residues under selection located at or close to active sites or at the dimer interface.We also reveal evidence of a correlation between ecological niches(e.g.high oxidative stress)and the divergent selection and gene copy number of GPX subclasses.Notably,a convergent expansion of GPX1 was observed in several independent lineages of mammals under oxidative stress and may be important for avoiding oxidative damage.Collectively,this study suggests that the GPX gene family has shaped the adaption of mammals to stressful environments.

Comparative analyses of aging-related genes in long-lived mammals provide insights into natural longevity

Extreme longevity has evolved multiple times during the evolution of mammals,yet its underlying molecular mechanisms remain largely underexplored.Here,we compared the evolution of 115 aging-related genes in 11 long-lived species and 25 mammals with non-increased lifespan(control group)in the hopes of better understanding the common molecular mechanisms behind longevity.We identified 16 unique positively selected genes and 23 rapidly evolving genes in long-lived species,which included nine genes involved in regulating lifespan through the insulin/IGF-1 signaling(IIS)pathway and 11 genes highly enriched in immune-response-related pathways,suggesting that the IIS pathway and immune response play a particularly important role in exceptional mammalian longevity.Interestingly,11 genes related to cancer progression,including four positively selected genes and seven genes with convergent amino acid changes,were shared by two or more long-lived lineages,indicating that long-lived mammals might have evolved convergent or similar mechanisms of cancer resistance that extended their lifespan.This suggestion was further corroborated by our identifi-cation of 12 robust candidates for longevity-related genes closely related to cancer.