Genomic insights into adaptation to bipedal saltation and desert-like habitats of jerboas

Jerboas is a lineage of small rodents displaying atypical mouse-like morphology with elongated strong hindlimbs and short forelimbs.They have evolved obligate bipedal saltation and acute senses,and been well-adapted to vast desert-like habitats.Using a newly sequenced chromosome-scale genome of the Mongolian five-toed jerboa(Orientallactaga sibirica),our comparative genomic analyses and in vitro functional assays showed that the genetic innovations in both protein-coding and non-coding regions played an important role in jerboa morphological and physiological adaptation.Jerboa-specific amino acid substitutions,and segment insertions/deletions(indels)in conserved non-coding elements(CNEs)were found in components of proteoglycan biosynthesis pathway(XYLT1 and CHSY1),which plays an important role in limb development.Meanwhile,we found specific evolutionary changes functionally associated with energy or water metabolism(e.g.,specific amino acid substitutions in ND5 and indels in CNEs physically near ROR2)and senses(e.g.,expansion of vomeronasal receptors and the FAM136A gene family)in jerboas.Further dual-luciferase reporter assay verified that some of the CNEs with jerboa-specific segment indels exerted a significantly different influence on luciferase activity,suggesting changes in their regulatory function in jerboas.Our results revealed the potential molecular mechanisms underlying jerboa adaptation since the divergence from the Eocene-Oligocene transition,and provided more resources and new insights to enhance our understanding of the molecular basis underlying the phenotypic diversity and the environmental adaptation of mammals.

The position of tree shrews in the mammalian tree:Comparing multi-gene analyses with phylogenomic results leaves monophyly of Euarchonta doubtful

The well-accepted Euarchonta grandorder is a pruned version of Archonta nested within the Euarchontoglires(or Supraprimates)clade.At present,it includes tree shrews(Scandentia),flying lemurs(Dermoptera)and primates(Primates).Here,a phylogenomic dataset containing 1912 exons from 22 representative mammals was compiled to investigate the phylogenetic relationships within this group.Phylogenetic analyses and hypothesis testing suggested that tree shrews can be classified as a sister group to Primates or to Glires or even as a basal clade within Euarchontoglires.Further analyses of both modified and original previously published datasets found that the phylogenetic position of tree shrews is unstable.We also found that two of three exonic indels reported as synapomorphies of Euarchonta in a previous study do not unambiguously support the monophyly of such a clade.Therefore,the monophyly of both Euarchonta and Sundatheria(Dermoptera+Scandentia)are suspect.Molecular dating and divergence rate analyses suggested that the ancestor of Euarchontoglires experienced a rapid divergence,which may cause the unresolved position of tree shrews even using the whole genomic data.

Evolutionary changes of Hox genes and relevant regulatory factors provide novel insights into mammalian morphological modifications

The diversity of body plans of mammals accelerates the innovation of lifestyles and the extensive adaptation to different habitats,including terrestrial,aerial and aquatic habitats.However,the genetic basis of those phenotypic modifications,which have occurred during mammalian evolution,remains poorly explored.In the present study,we synthetically surveyed the evolutionary pattern of Hox clusters that played a powerful role in the morphogenesis along the head-tail axis of animal embryos and the main regulatory factors(Mll,Bmi1 and E2f6)that control the expression of Hox genes.A deflected density of repetitive elements and lineage-specific radical mutations of Mll have been determined in marine mammals with morphological changes,suggesting that evolutionary changes may alter Hox gene expression in these lineages,leading to the morphological modification of these lineages.Although no positive selection was detected at certain ancestor nodes of lineages,the increasedωvalues of Hox genes implied the relaxation of functional constraints of these genes during the mammalian evolutionary process.More importantly,49 positively-selected sites were identified in mammalian lineages with phenotypic modifications,indicating adaptive evolution acting on Hox genes and regulatory factors.In addition,3 parallel amino acid substitutions in some Hox genes were examined in marine mammals,which might be responsible for their streamlined body.

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.

Tramadol reinforces antidepressant effects of ketamine with increased levels of brain-derived neurotrophic factor and tropomyosin-related kinase B in rat hippocampus

Ketamine exerts rapid and robust antidepressant properties in both animal models and depressed patients and tramadol possesses potential antidepressant effects.Brain-derived neurotrophic factor(BDNF)is an important biomarker for mood disorders and tropomyosin-related kinase B(TrkB)is a high affinity catalytic receptor for BDNF.We hypothesized that tramadol pretreatment might reinforce ketamine-elicited antidepressant effects with significant changes in hippocampal BDNF and TrkB levels in rats.Immobility time of rats receiving different treatment in the forced swimming test(FST)was observed.Levels of BDNF and TrkB in hippocampus were measured by enzyme linked immunosorbent assay.Results showed that tramadol(5 mg/kg)administrated alone neither elicited antidepressant effects nor altered BDNF or TrkB level.However,pretreatment with tramadol(5 mg/kg)enhanced the ketamine(10 mg/kg)-elicited antidepressant effects and upregulated the BDNF and TrkB levels in hippocampus.In conclusion,tramadol pretreatment reinforces the ketamine-elicited antidepressant effects,which is associated with the increased levels of BDNF and TrkB in rat hippocampus.

Molecular evolution of spermatogenesis-related genes in abdominal testicular mammals supports the cooling hypothesis

Testes,which are mainly responsible for producing sperm and secreting male hormones,are the functional center of the male reproductive system in mammals.During embryonic development in mammals with descended testes,the testicles descend from the urogenital ridge to the scrotum,located outside the body cavity (Hutson et al.,2015).