Patterns of Coevolutionary Adaptations across Time and Space in Mouse Gammaretroviruses and Three Restrictive Host Factors

The classical laboratory mouse strains are genetic mosaics of three Mus musculus subspecies that occupy distinct regions of Eurasia. These strains and subspecies carry infectious and endogenous mouse leukemia viruses (MLVs) that can be pathogenic and mutagenic. MLVs evolved in concert with restrictive host factors with some under positive selection, including the XPR1 receptor for xenotropic/polytropic MLVs (X/P-MLVs) and the post-entry restriction factor Fv1. Since positive selection marks host-pathogen genetic conflicts, we examined MLVs for counter-adaptations at sites that interact with XPR1, Fv1, and the CAT1 receptor for ecotropic MLVs (E-MLVs). Results describe different co-adaptive evolutionary paths within the ranges occupied by these virus-infected subspecies. The interface of CAT1, and the otherwise variable E-MLV envelopes, is highly conserved; antiviral protection is afforded by the Fv4 restriction factor. XPR1 and X/P-MLVs variants show coordinate geographic distributions, with receptor critical sites in envelope, under positive selection but with little variation in envelope and XPR1 in mice carrying P-ERVs. The major Fv1 target in the viral capsid is under positive selection, and the distribution of Fv1 alleles is subspecies-correlated. These data document adaptive, spatial and temporal, co-evolutionary trajectories at the critical interfaces of MLVs and the host factors that restrict their replication.

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Wild mouse RNA tumor viruses. A nongenetically transmitted virus group closely related to exogenous leukemia viruses of laboratory mouse strains.

Journal of Experimental Medicine ◽

10.1084/jem.149.1.254 ◽

1979 ◽

Vol 149 (1) ◽

pp. 254-266 ◽

Cited By ~ 21

Author(s):

M Barbacid ◽

K C Robbins ◽

S A Aaronson

Keyword(s):

Laboratory Mouse ◽

Wild Mouse ◽

Mouse Strains ◽

Wild Mice ◽

Virus Group ◽

Tumor Viruses ◽

Antigenic Relatedness ◽

Endogenous Viruses ◽

Type C ◽

Leukemia Viruses

Type-C RNA viruses isolated from wild mice are causative of naturally occurring neoplasia and neurologic diseases. Biochemical and immunologic characterization of this virus group revealed that amphotropic viruses isolated from wild mice trapped in separate geographical areas are indistinguishable, whereas amphotropic and ecotropic viruses naturally infecting the same animal are env gene variants. Molecular hybridization studies established that neither host range variant is endogenous to the Mus musculus genome, although each demonstrates partial nucleotide sequence homology. Wild mouse type-C viruses exhibited much closer molecular and antigenic relatedness to the exogenous virus subgroup (Friend-, Moloney-, and Rauscher-MuLV) than to prototype endogenous viruses isolated from laboratory mouse strains. The evidence indicates that exogenous mouse type-C viruses have been maintained in nature over a long period of evolution as a separate virus group, causative of tumors in mice by a mechanism solely involving their transmission as infectious agents.

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Quantitating Aortic Atherosclerosis in Rabbits and Mice

Microscopy and Microanalysis ◽

10.1017/s1431927600008473 ◽

1997 ◽

Vol 3 (S2) ◽

pp. 317-318

Author(s):

David A. Sanan ◽

Dale L. Newland

Keyword(s):

Gene Knockout ◽

Laboratory Mouse ◽

Lipoprotein Metabolism ◽

Wild Type Mouse ◽

Mouse Strains ◽

Chow Diet ◽

Homologous Genes ◽

Normal Chow ◽

Metabolism Gene ◽

Knockout Technology

Build-up of visible atherosclerotic plaque in the arteries is readily quantifiable. The mouse and the rabbit provide useful models for understanding the pathogenesis of atherosclerosis by investigating the effects of genetic and dietary perturbations.Although the wild type mouse does not develop atherosclerosis, atherosclerosis susceptibility genes have been identified in some laboratory mouse strains which do. Furthermore, transgenic technology and gene targeting have produced genetically modified mice that express various apolipoproteins, enzymes and cofactors involved in human lipoprotein metabolism. Gene “knockout” technology allows transgene expression without interference from homologous genes. One notable “knockout” mouse, deficient in apolipoprotein E, develops spontaneous atherosclerosis on a normal chow diet. Transgenic modulations of the atherosclerotic responses of these highly susceptible mice are more pronounced and easily measured. Small, cheap and fast breeding, mice are convenient animal models. But to make mice susceptible to atherosclerosis, their genetic background has to be so drastically altered that the resulting lipoprotein metabolism may not model the human metabolism accurately enough.

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Smc5/6-antagonism by HBx is an evolutionary-conserved function of hepatitis B virus infection in mammals

10.1101/202671 ◽

2017 ◽

Cited By ~ 1

Author(s):

Fabien Filleton ◽

Fabien Abdul ◽

Laetitia Gerossier ◽

Alexia Paturel ◽

Janet Hall ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Antiviral Activity ◽

Positive Selection ◽

Host Species ◽

Human Hepatocytes ◽

Arms Race ◽

Restriction Factor ◽

Primary Human Hepatocytes ◽

B Virus

AbstractInfection with Hepatitis B virus (HBV) is a major cause of liver disease and cancer in humans. HBVs (family Hepadnaviridae) have been associated with mammals for millions of years. Recently, the Smc5/6 complex, known for its essential housekeeping functions in genome maintenance, was identified as an antiviral restriction factor of human HBV. The virus has however developed a counteraction mechanism by degrading the complex via its regulatory HBx protein. Whether the antiviral activity of the Smc5/6 complex against hepadnaviruses is an important and evolutionary-conserved function is unknown. Here, we used a combined evolutionary and functional approach to address this question. We first performed phylogenetic and positive selection analyses of the six Smc5/6 complex subunits and found that they have been highly conserved in primates and mammals. Yet, the Smc6 subunit showed marks of adaptive evolution, potentially reminiscent of virus-host “arms-race” We then functionally tested the HBx from six very divergent hepadnaviruses now naturally infecting primates, rodents, and bats. Despite little sequence homology, we demonstrate that these HBx efficiently degraded mammalian Smc5/6 complexes, independently of the host species and of the sites under positive selection. Importantly, all also rescued the replication of an HBx-deficient HBV in primary human hepatocytes. These findings point to an evolutionary-conserved requirement for Smc5/6 inactivation by HBx, showing that the Smc5/6 antiviral activity has been an important defense mechanism against hepadnaviruses in mammals. Interestingly, Smc5/6 may further be a restriction factor of other yet unidentified viruses that have driven some of its adaptation.ImportanceInfection with hepatitis B virus (HBV) led to 887000 human deaths in 2015. HBV has been co-evolving with mammals for millions of years. Recently, the Smc5/6 complex, known for its essential housekeeping functions, was identified as a restriction factor of human HBV antagonized by the regulatory HBx protein. Here, we address whether the antiviral activity of Smc5/6 is an important evolutionary-conserved function. We found that all six subunits of Smc5/6 have been conserved in primates with only Smc6 showing signatures of “evolutionary arms-race” Using evolutionary-guided functional assays that include infections of primary human hepatocytes, we demonstrate that HBx from very divergent mammalian HBVs could all efficiently antagonize Smc5/6, independently of the host species and sites under positive selection. These findings show that the Smc5/6 antiviral activity against HBV is an important function in mammals. It also raises the intriguing possibility that Smc5/6 restricts other, yet unidentified viruses.

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MoG+: a database of genomic variations across three mouse subspecies for biomedical research

Mammalian Genome ◽

10.1007/s00335-021-09933-w ◽

2021 ◽

Author(s):

Toyoyuki Takada ◽

Kentaro Fukuta ◽

Daiki Usuda ◽

Tatsuya Kushida ◽

Shinji Kondo ◽

...

Keyword(s):

Phenotypic Diversity ◽

Laboratory Mouse ◽

Genomic Analysis ◽

Inbred Strains ◽

Genetic Distances ◽

Mouse Strains ◽

Comparative Genomic ◽

Genome Database ◽

Data Resource ◽

Genomic Variations

AbstractLaboratory mouse strains have mosaic genomes derived from at least three major subspecies that are distributed in Eurasia. Here, we describe genomic variations in ten inbred strains: Mus musculus musculus-derived BLG2/Ms, NJL/Ms, CHD/Ms, SWN/Ms, and KJR/Ms; M. m. domesticus-derived PGN2/Ms and BFM/Ms; M. m. castaneus-derived HMI/Ms; and JF1/Ms and MSM/Ms, which were derived from a hybrid between M. m. musculus and M. m. castaneus. These strains were established by Prof. Moriwaki in the 1980s and are collectively named the “Mishima Battery”. These strains show large phenotypic variations in body size and in many physiological traits. We resequenced the genomes of the Mishima Battery strains and performed a comparative genomic analysis with dbSNP data. More than 81 million nucleotide coordinates were identified as variant sites due to the large genetic distances among the mouse subspecies; 8,062,070 new SNP sites were detected in this study, and these may underlie the large phenotypic diversity observed in the Mishima Battery. The new information was collected in a reconstructed genome database, termed MoG+ that includes new application software and viewers. MoG+ intuitively visualizes nucleotide variants in genes and intergenic regions, and amino acid substitutions across the three mouse subspecies. We report statistical data from the resequencing and comparative genomic analyses and newly collected phenotype data of the Mishima Battery, and provide a brief description of the functions of MoG+, which provides a searchable and unique data resource of the numerous genomic variations across the three mouse subspecies. The data in MoG+ will be invaluable for research into phenotype-genotype links in diverse mouse strains.

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Distinct evolutionary trajectories of V1R clades across mouse species

10.21203/rs.2.22451/v3 ◽

2020 ◽

Author(s):

Caitlin H Miller ◽

Polly Campbell ◽

Michael J Sheehan

Keyword(s):

Positive Selection ◽

House Mouse ◽

Gene Family Evolution ◽

Specific Gene ◽

Receptor Subtypes ◽

Gene Repertoire ◽

Social Signals ◽

Functional Roles ◽

Wide Range ◽

Evolutionary Trajectories

Abstract BACKGROUND: Many animals rely heavily on olfaction to navigate their environment. Among rodents, olfaction is crucial for a wide range of social behaviors. The vomeronasal olfactory system in particular plays an important role in mediating social communication, including the detection of pheromones and recognition signals. In this study we examine patterns of vomeronasal type-1 receptor (V1R) evolution in the house mouse and related species within the genus Mus . We report the extent of gene repertoire turnover and conservation among species and clades, as well as the prevalence of positive selection on gene sequences across the V1R tree. By exploring the evolution of these receptors, we provide insight into the functional roles of receptor subtypes as well as the dynamics of gene family evolution. RESULTS: We generated transcriptomes from the vomeronasal organs of 5 Mus species, and produced high quality V1R repertoires for each species. We find that V1R clades in the house mouse and relatives exhibit distinct evolutionary trajectories. We identify putative species-specific gene expansions, including a large clade D expansion in the house mouse. While gene gains are abundant, we detect very few gene losses. We describe a novel V1R clade and highlight candidate receptors for future study. We find evidence for distinct evolutionary processes across different clades, from largescale turnover to highly conserved repertoires. Patterns of positive selection are similarly variable, as some clades exhibit abundant positive selection while others display high gene sequence conservation. Based on clade-level evolutionary patterns, we identify receptor families that are strong candidates for detecting social signals and predator cues. Our results reveal clades with receptors detecting female reproductive status are among the most conserved across species, suggesting an important role in V1R chemosensation. CONCLUSION: Analysis of clade-level evolution is critical for understanding species’ chemosensory adaptations. This study provides clear evidence that V1R clades are characterized by distinct evolutionary trajectories. As receptor evolution is shaped by ligand identity, these results provide a framework for examining the functional roles of receptors.

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Molecular Basis for Variable Expression of the MHC Class III Complement Genes, C4 and Slp, among Wild-Derived and Laboratory Mouse Strains

Genetics In Wild Mice ◽

10.1159/000424161 ◽

2015 ◽

pp. 229-234

Author(s):

Masaru Nonaka

Keyword(s):

Molecular Basis ◽

Laboratory Mouse ◽

Mouse Strains ◽

Class Iii ◽

Variable Expression ◽

Mhc Class Iii

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Generic Homo sapiens and Unique Mus musculus: Establishing the Typicality of the Modeled and the Model Species

Brain Behavior and Evolution ◽

10.1159/000500111 ◽

2019 ◽

Vol 93 (2-3) ◽

pp. 122-136 ◽

Cited By ~ 1

Author(s):

Barbara L. Finlay

Keyword(s):

Neural Development ◽

Functional Organization ◽

Homo Sapiens ◽

Laboratory Mouse ◽

Mouse Strains ◽

Human Species ◽

Model Species ◽

Brain Mass ◽

Multiple Strategies ◽

Neural Architecture

The question of how complex human abilities evolved, such as language or face recognition, has been pursued by means of multiple strategies. Highly specialized non-human species have been examined analytically for formal similarities, close phylogenetic relatives have been examined for continuity, and simpler species have been analyzed for the broadest view of functional organization. All these strategies require empirical evidence of what is variable and predictable in both the modeled and the model species. Turning to humans, allometric analyses of the evolution of brain mass and brain components often return the interesting, but disappointing answer that volumetric organization of the human brain is highly predictable seen in its phylogenetic context. Reconciling this insight with unique human behavior, or any species-typical behavior, represents a serious challenge. Allometric analyses of the order and duration of mammalian neural development show that, while basic neural development in humans is allometrically predictable, conforming to adult neural architecture, some life history features deviate, notably that weaning is unusually early. Finally, unusual deviations in the retina and central auditory system in the laboratory mouse, which is widely assumed to be “generic,” as well as severe deviations from expected brain allometry in some mouse strains, underline the need for a deeper understanding of phylogenetic variability even in those systems believed to be best understood.

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Immunity toTrichuris murisin the laboratory mouse

Journal of Helminthology ◽

10.1079/joh2002162 ◽

2003 ◽

Vol 77 (2) ◽

pp. 95-98 ◽

Cited By ~ 12

Author(s):

K.J. Else ◽

M.L. deSchoolmeester

Keyword(s):

Laboratory Mouse ◽

Mouse Strains ◽

Chronic Infections ◽

Trichuris Muris ◽

Intestinal Nematode ◽

Unique Model ◽

Resistance To Infection ◽

Laboratory Models ◽

Strain Dependent

AbstractOf all the laboratory models of intestinal nematode infection,Trichuris murisin the mouse is arguably the most powerful. This is largely due to the fact that the ability to expel this parasite is strain dependent. Thus, most mouse strains readily expelT. muris. However certain mouse strains, and indeed some individuals within particular mouse strains, are unable to mount a protective immune response and harbour long term chronic infections. This unique model thus presents an opportunity to examine the immune events underlying both resistance to infection and persistent infection within the same host species, and in some cases, the same host strain.

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Evolution of Functional and Sequence Variants of the Mammalian XPR1 Receptor for Mouse Xenotropic Gammaretroviruses and the Human-Derived Retrovirus XMRV

Journal of Virology ◽

10.1128/jvi.01549-10 ◽

2010 ◽

Vol 84 (22) ◽

pp. 11970-11980 ◽

Cited By ~ 27

Author(s):

Yuhe Yan ◽

Qingping Liu ◽

Kurt Wollenberg ◽

Carrie Martin ◽

Alicia Buckler-White ◽

...

Keyword(s):

Virus Entry ◽

Leukemia Virus ◽

Laboratory Mouse ◽

Wild Mouse ◽

Chronic Fatigue ◽

Receptor Function ◽

Fatigue Syndrome ◽

Novel Host ◽

History Of ◽

Leukemia Viruses

ABSTRACT Genetic conflicts between retroviruses and their receptors result in the evolution of novel host entry restrictions and novel virus envelopes, and such variants can influence trans-species transmission. We screened rodents and other mammals for sequence variation in the Xpr1 receptor for the mouse xenotropic or polytropic mouse leukemia viruses (X-MLVs or P-MLVs, respectively) of the gammaretrovirus family and for susceptibility to mouse-derived X/P-MLVs and to XMRV (xenotropic murine leukemia virus-related virus), an X-MLV-like virus isolated from humans with prostate cancer and chronic fatigue syndrome. We identified multiple distinct susceptibility phenotypes; these include the four known Xpr1 variants in Mus and a novel fifth Xpr1 gene found in Mus molossinus and Mus musculus. We describe the geographic and species distribution of the Mus Xpr1 variants but failed to find the X-MLV-restrictive laboratory mouse allele in any wild mouse. We used mutagenesis and phylogenetic analysis to evaluate the functional contributions made by constrained, variable, and deleted residues. Rodent Xpr1 is under positive selection, indicating a history of host-pathogen conflicts; several codons under selection have known roles in virus entry. All non-Mus mammals are susceptible to mouse X-MLVs, but some restrict other members of the X/P-MLV family, and the resistance of hamster and gerbil cells to XMRV indicates that XMRV has unique receptor requirements. We show that the hypervariable fourth extracellular XPR1 loop (ECL4) contains three evolutionarily constrained residues that do not contribute to receptor function, we identify two novel residues important for virus entry (I579 and T583), and we describe a unique pattern of ECL4 variation in the three virus-restrictive Xpr1 variants found in MLV-infected house mice; these mice carry different deletions in ECL4, suggesting either that these sites or loop size affects receptor function.

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