Comparative genome mapping of the deer mouse (<Emphasis Type="Italic">Peromyscus maniculatus</Emphasis>) reveals greater similarity to rat (<Emphasis Type="Italic">Rattus norvegicus</Emphasis>) than to the lab mouse (<Emphasis Type="Italic">Mus musculus</Emphasis>)

Background  

Deer mice (Peromyscus maniculatus) and congeneric species are the most common North American mammals. They represent an emerging system for the genetic analyses of the physiological and behavioral bases of habitat adaptation. Phylogenetic evidence suggests a much more ancient divergence of Peromyscus from laboratory mice (Mus) and rats (Rattus) than that separating latter two. Nevertheless, early karyotypic analyses of the three groups suggest Peromyscus to be exhibit greater similarities with Rattus than with Mus.     

A genetic map of Peromyscus with chromosomal assignment of linkage groups (a Peromyscus genetic map)

The rodent genus Peromyscus is the most numerous and species-rich mammalian group in North America. The naturally occurring diversity within this genus allows opportunities to investigate the genetic basis of adaptation, monogamy, behavioral and physiological phenotypes, growth control, genomic imprinting, and disease processes. Increased genomic resources including a high quality genetic map are needed to capitalize on these opportunities. We produced interspecific hybrids between the prairie deer mouse (P. maniculatus bairdii) and the oldfield mouse (P. polionotus) and scored meiotic recombination events in backcross progeny. A genetic map was constructed by genotyping of backcross progeny at 185 gene-based and 155 microsatellite markers representing all autosomes and the X-chromosome. Comparison of the constructed genetic map with the molecular maps of Mus and Rattus and consideration of previous results from interspecific reciprocal whole chromosome painting allowed most linkage groups to be unambiguously assigned to specific Peromyscus chromosomes. Based on genomic comparisons, this Peromyscus genetic map covers ~83 % of the Rattus genome and 79 % of the Mus genome. This map supports previous results that the Peromyscus genome is more similar to Rattus than Mus. For example, coverage of the 20 Rattus autosomes and the X-chromosome is accomplished with only 28 segments of the Peromyscus map, but coverage of the 19 Mus autosomes and the X-chromosome requires 40 chromosomal segments of the Peromyscus map. Furthermore, a single Peromyscus linkage group corresponds to about 91 % of the rat and only 76 % of the mouse X-chromosomes.     

Mus and Peromyscus chromosome homology established by FISH with three mouse paint probes

Fluorescence-labeled DNA probes constructed from three whole house mouse (Mus domesticus) chromosomes were hybridized to metaphase spreads from deer mouse (Peromyscus maniculatus) to identify homologies between the species. Mus Chr 7 probe hybridized strongly to the ad-centromeric two-thirds of Peromyscus Chr 1q. Most of Mus 3 probe hybridized principally to two disjunct segments of Peromyscus Chr 3. Mus Chr 9 probe hybridized entirely to the whole Peromyscus Chr 7. Three Peromyscus linkage groups were assigned to chromosomes, based on linkage homology with Mus. The data also are useful in interpretation of chromosomal evolutionary history in myomorphic rodents. Received: 1 December 1998 / Accepted: 17 February 1999     

Estrogen Receptor Alpha Distribution and Expression in the Social Neural Network of Monogamous and Polygynous Peromyscus

In microtine and dwarf hamsters low levels of estrogen receptor alpha (ERα) in the bed nucleus of the stria terminalis (BST) and medial amygdala (MeA) play a critical role in the expression of social monogamy in males, which is characterized by high levels of affiliation and low levels of aggression. In contrast, monogamous Peromyscus males display high levels of aggression and affiliative behavior with high levels of testosterone and aromatase activity. Suggesting the hypothesis that in Peromyscus ERα expression will be positively correlated with high levels of male prosocial behavior and aggression. ERα expression was compared within the social neural network, including the posterior medial BST, MeA posterodorsal, medial preoptic area (MPOA), ventromedial hypothalamus (VMH), and arcuate nucleus in two monogamous species, P. californicus and P. polionotus, and two polygynous species, P. leucopus and P. maniculatus. The results supported the prediction, with male P. polionotus and P. californicus expressing higher levels of ERα in the BST than their polygynous counter parts, and ERα expression was sexually dimorphic in the polygynous species, with females expressing significantly more than males in the BST in both polygynous species and in the MeA in P. leucopus. Peromyscus ERα expression also differed from rats, mice and microtines as in neither the MPOA nor the VMH was ERα sexually dimorphic. The results supported the hypothesis that higher levels of ERα are associated with monogamy in Peromyscus and that differential expression of ERα occurs in the same regions of the brains regardless of whether high or low expression is associated with social monogamy. Also discussed are possible mechanisms regulating this differential relationship.     

Variation in the genetic structure of Peromyscus populations. I. Genetic heterozygosity—its relationship to adaptive divergence

The genetic structure of nine Peromyscus maniculatus nebrascensis demes from southeastern Wyoming was determined by analyzing allozymes encoded by 23 genetic loci with polyacrylamide gel electrophoresis. Genetic variability is extremely high for two genetic parameters; the proportion of loci heterozygous per individual averaged 0.16, and the proportion of loci polymorphic per deme averaged 0.41. Previous estimates of genetic heterozygosity for species within the genus Peromyscus have a mean of 0.06. The results of the present study suggest that genetic heterozygosity is considerably higher within P. maniculatus demes than within demes of other species in the genus. Geographic range is correlated with heterozygosity among Peromyscus species, as is adaptive divergence into broad-niched species. These correlates suggest that high heterozygosity may reflect an adaptation to a variable environment.     

Divergent patterns of breakpoint reuse in Muroid rodents

Multiple Genome Rearrangement (MGR) analysis was used to define the trajectory and pattern of chromosome rearrangement within muroid rodents. MGR was applied using 107 chromosome homologies between Mus, Rattus, Peromyscus, the muroid sister taxon Cricetulus griseus, and Sciurus carolinensis as a non-Muroidea outgroup, with specific attention paid to breakpoint reuse and centromere evolution. This analysis revealed a high level of chromosome breakpoint conservation between Rattus and Peromyscus and indicated that the chromosomes of Mus are highly derived. This analysis identified several conserved evolutionary breakpoints that have been reused multiple times during karyotypic evolution in rodents. Our data demonstrate a high level of reuse of breakpoints among muroid rodents, further supporting the “Fragile Breakage Model” of chromosome evolution. We provide the first analysis of rodent centromeres with respect to evolutionary breakpoints. By analyzing closely related rodent species we were able to clarify muroid rodent karyotypic evolution. We were also able to derive several high-resolution ancestral karyotypes and identify rearrangements specific to various stages of Muroidea evolution. These data were useful in further characterizing lineage-specific modes of chromosome evolution.     

Live animal radiography to measure developmental instability in populations of small mammals after a natural disaster

Stress placed on individuals in a population from natural and anthropogenic disturbances can elevate developmental instability. We studied the result of a natural disaster when one-third of a forested nature preserve was destroyed by an F3 tornado. Populations of two abundant species of small mammals, Peromyscus maniculatus and P. leucopus, were monitored in both disturbed and undisturbed habitats. We used an X-ray technique to measure developmental instability as indicated by fluctuating asymmetry (FA) in cranial and skeletal features of live animals. FA in femur length was higher in disturbed habitat for P. leucopus but was higher in undisturbed habitat for P. maniculatus. This difference in developmental instability mirrors differences in habitat preference between these species: P. leucopus prefers forest habitat and P. maniculatus prefers open, herbaceous habitat. These results were not explained by either food availability or body condition, both of which were higher in the disturbed habitat suggesting higher quality for this habitat. Thus, the FA response may be related to other indicators of habitat quality, e.g., vertical stratification, coarse-woody debris, or population density, which may differ between undisturbed and disturbed habitats.     

Retrotransposon Mys was active during evolution of the Peromyscus leucopus-maniculatus complex

Mys is a retrovirus-like transposable element found throughout the genus Peromyscus. Several mys subfamilies identified on the basis of restriction site variation occur in more than one species. The distribution of these subfamilies is consistent with the accepted species phylogeny, suggesting that mys was present in the ancestor of Peromyscus and has been active through much of the evolution of this genus. Quantitative Southern blot analysis was used to examine the variability of subfamilies in P. leucopus and maniculatus. We found that subfamilies with phylogenetically narrow distributions were more variable in copy number both within and between species than subfamilies with a broader distribution. Taken together, our data suggest that mys has undergone multiple rounds of transposition since the peromyscine radiation, and that five subfamilies have been amplified during the evolution of the leucopus-maniculatus species complex. Correspondence to: H.A. Wichman     

Microhabitat segregation in two desert rodent species: the relation of prey availability to diet

Summary I studied diet in relation to microhabitat use in two desert rodents:Microdipodops megacephalus, the dark kangaroo mouse, andPeromyscus maniculatus, the deer mouse. Contrary to expectation, both species ate primarily arthropods, which were most abundant near shrubs.Peromyscus used the area near shrubs, in contrast toMicrodipodops, which used open microhabitat. As a consequence, the diet ofPeromyscus was narrower and more concentrated on abundant prey types than that ofMicrodipodops. Thus microhabitat segregation, which is frequently reported for desert rodents, is related to a diet-breadth difference between these rodents. The use of open microhabitat and low density resources byMicrodipodops, when compared with the large bipedalDipodomys and small quadrupedalPerognatus, suggests that bipedal locomotion in desert rodents is related to use of open microhabitat, and that body size is related to density of food resources.     

Rapid morphological divergence in two closely related and co-occurring species over the last 50 years

We studied morphological variation in two closely related and ecologically similar species of mice of the genus Peromyscus, the deer mouse (P. maniculatus) and white-footed mouse (P. leucopus), over the last 50 years in Southern Quebec. We found that contemporary populations of the two species are distinct in morphology and interpret this differentiation as a reflection of resource partitioning, a mechanism favouring their local coexistence. While there was no size trend, geographic or temporal, both species displayed a concomitant change in the shape of their skull over the last 50 years, although this change was much more apparent in the white-footed mouse. As a result, the two species diverged over time and became more distinct in their morphology. The observed changes in morphology are large given the short time scale. During this period, there was also a shift in abundance of the two species in Southern Quebec, consistent with the northern displacement of the range of the white-footed mouse in the last 15 years. Our study thus reports the changes in morphology of two co-occurring mammal species that were accompanied by changes in distribution and local abundance, potentially in response to rapid climate change.     

Genetic Analysis of the Diversity and Origin of Hantaviruses in Peromyscus leucopus Mice in North America

Nucleotide sequences were determined for the complete M genome segments of two distinct hantavirus genetic lineages which were detected in hantavirus antibody- and PCR-positive white-footed mice (Peromyscus leucopus) from Indiana and Oklahoma. Phylogenetic analyses indicated that although divergent from each other, the virus lineages in Indiana and Oklahoma were monophyletic and formed a newly identified unique ancestral branch within the clade of Sin Nombre-like viruses found in Peromyscus mice. Interestingly, P. leucopus-borne New York virus was found to be most closely related to the P. maniculatus-borne viruses, Sin Nombre and Monongahela, and monophyletic with Monongahela virus. In parallel, intraspecific phylogenetic relationships of P. leucopus were also determined, based on the amplification, sequencing, and analysis of the DNA fragment representing the replication control region of the rodent mitochondrial genome. P. leucopus mitochondrial DNA haplotypes were found to form four separate genetic clades, referred to here as Eastern, Central, Northwestern, and Southwestern groups. The distinct Indiana and Oklahoma virus lineages were detected in P. leucopus of the Eastern and Southwestern mitochondrial DNA haplotypes, respectively. Taken together, our current data suggests that both cospeciation of Peromyscus-borne hantaviruses with their specific rodent hosts and biogeographic factors (such as allopatric migrations, geographic separation, and isolation) have played important roles in establishment of the current genetic diversity and geographic distribution of Sin Nombre-like hantaviruses. In particular, the unusual position of New York virus on the virus phylogenetic tree is most consistent with an historically recent host-switching event.     

Evolutionary conservation of linkage groups: Additional evidence from murid and cricetid rodents

In Mus musculus, family Muridae, the glucosephosphate isomerase (Gpi-1), pink-eyed dilution (p), albinism (c), and -type globin (Hbb) loci are known to be linked in the order Gpi-1-p-c-Hbb. In Rattus norvegicus, another murid rodent, the p, c, and Hbb loci are known to be linked in the same order and with similar recombination frequencies. In Peromyscus maniculatus, family Cricetidae, it was previously known that p and c are linked and by analogy to Mus musculus that linkage group should be bounded by Gpi-1 near p and by a -globin locus near c. Linkage has now been established between Gpi-1 and the Hbe globin locus in Peromyscus. However, the observed recombination frequency in Peromyscus (16.3%) is significantly lower than in Mus, suggesting that perhaps a chromosomal inversion has occurred during the evolutionary divergence of the two rodent families. Linkage relationships were also tested between the Hbc ¹, Hbd ¹, and Hbe ¹ globin variants. Hbc ¹ (presumably an -type globin) segregated independently from Hbd ¹ and Hbe ¹ (presumably -type globins). No recombination was observed between Hbd ¹ and Hbe ¹. Those two globin genes may be alleles at a single locus, although circumstantial evidence suggests that they represent tightly linked duplicate loci.This work was supported by NSF DEB7716104 and by the Committee on Research, UCR.     

The effect of sub-lethal doses of bromadiolone on the breeding performance of house mice (Mus domesticus)

Both laboratory and field strains of Mus were exposed to wheat containing 0.0001% bromadiolone under laboratory and outdoor conditions, respectively. While both strains readily consumed the poisoned wheat, ad libitum sub-lethal doses of this anticoagulant equating to between 20% and 70% of the acute ld₅₀ per feed had little apparent effect on the breeding performance of these mice. The implications of these findings are discussed with respect to the use of anticoagulants as pesticides.     

Bacterial Species-Specific Activity of a Fluoroquinolone against Two Closely Related Pasteurellaceae with Similar MICs: Differential In Vitro Inoculum Effects and In Vivo Efficacies

We investigated the antimicrobial activity of a fluoroquinolone against two genetically close bacterial species belonging to the Pasteurellaceae family. Time-kill experiments were used to measure the in vitro activity of marbofloxacin against two strains of Mannheimia haemolytica and Pasteurella multocida with similar MICs. We observed that marbofloxacin was equally potent against 10⁵ CFU/mL inocula M. haemolytica and P. multocida. However, an inoculum effect was observed with P. multocida, meaning that marbofloxacin activity was decreased against a 10⁸ CFU/mL inoculum, whereas no inoculum effect was observed with M. haemolytica. Marbofloxacin activity was also tested in a lung infection model with immunocompromised mice intratracheally infected with 10⁹ CFU of each bacteria. At the same dose, the clinical and bacteriological outcomes were much better for mice infected with M. haemolytica than for those infected with P. multocida. Moreover, bacteriological eradication was obtained with a lower marbofloxacin dose for mice infected with M. haemolytica. Our results suggest that the differential in vivo marbofloxacin efficacy observed with the two bacterial species of similar MIC could be explained by a differential inoculum effect. Consequently, MICs determined on 10⁵ CFU inocula were not predictive of the differences in antibiotic efficacies against high bacterial inocula of closely related bacterial strains. These results could stimulate further investigations on bacterial species-specific antibiotic doses in a clinical setting.     

Development of a deer mouse whole-genome radiation hybrid panel and comparative mapping of Mus chromosome 11 loci

A 5000-rad whole-genome radiation hybrid cell panel (BW5000) was developed for mapping the deer mouse (Peromyscus maniculatus bairdii) genome. The panel consists of 103 cell lines and has an estimated marker retention frequency of 63.9% (range, 28%–88%) based on PCR typing of 30 Type I (coding gene) and 25 Type II (microsatellite) markers. Using the composite Mus map, Type I markers were selected from six Mus chromosomes, 22 of which are on Mus Chr 11. Fifteen of the Mus Chr 11 markers were simultaneously mapped on an interspecific (P. maniculatus × P. polionotus) backcross panel to test the utility of the radiation hybrid panel, create a framework map, and help establish gene order. The radiation hybrids have effectively detected linkage in the deer mouse genome between markers as far apart as 6.7 cM and resolved markers that are, in the Mus genome, as close as 0.2 Mb. Combined results from both panels have indicated a high degree of gene order conservation of the telomeric 64 cM of Mus Chr 11 in the deer mouse genome. The remaining centromeric portion also shows gene order conservation with the deer mouse but as a separate linkage group. This indicates a translocation of that portion of Mus Chr 11 in P. maniculatus and is consistent with rearrangement breakpoints observed between Mus and other mammalian genomes, including rat and human. Furthermore, this separate linkage group is likely to reside in a chromosomal region of inversion polymorphism between P. maniculatus and P. polionotus.     

Influence of serum donor and recipient mouse genotype on the passive transfer of protective immunity with serum against Nematospiroides dubius

Dobson C., Brindley P. J. and Sitepu P. 1982. Influence of serum donor and recipient mouse genotype on the passive transfer of protective immunity with serum against Nematospiroides dubius. International Journal for Parasitology12: 567–572. Different strains of serum donor mice showed variations in innate immunity to primary infections with Nematospiroides dubius. Different levels of anti-N, dubius antibodies were detected in sera from these mouse strains; there was no correlation between antibody titre and numbers of worms recovered. Serum from donor wild and six laboratory strains of mice protected female Quackenbush (Q) recipients against N. dubius infections; donor mouse strain influenced the degree of protection conferred and donor serum antibody titre related to the degree of stunting of worm growth in recipient mice. Five laboratory strains of mice developed different levels of protective immunity following multiple experimental infections with N. dubius. Antibody titres in these mice were strongly correlated with the percentage protection observed after 1–4 infections: Q and CBA mice produced more anti-N. dubius antibody and were better protected than DBA/2, BALB/c and C3H mice. However BALB/c, C3H and CBA mice attained similar anti-N. dubius antibody titres after a single infection with N. dubius but serum from BALB/c gave better protection when transferred to female Q recipients than that from the other two strains. This suggested qualitative differences in the protective antibodies in sera between mouse strains. Five mouse strains were passively immunized with a uniform dose of serum from female Q donors: DBA/2 female recipients showed the least, BALB/c and C3H females were intermediate, and Q and CBA female mice attained the greatest level of passive protection against N. dubius. A close positive correlation existed between the degree of actively acquired and the level of passively acquired protection between the five strains of mice.     

Aggression between weanling Peromyscus and Microtus

Microtus pennsylvanicus were attacked by weanling Peromyscus of all three species tested: P. leucopus noveboracensis, P. maniculatus bairdii, and P. polionotus (colemani). However, defensive behaviours were more frequent than aggressive behaviours. Of the three species of Peremyscus tested, P. m. bairdii are most likely to meet Microtus in the field and displayed more agonistic behaviours in the laboratory. Female Peromyscus of all species tested were as likely to engage in all agonistic behaviours as were males. Inter-generic aggression developed before intra-generic aggression.     

Differences in daily torpor patterns among three southeastern species ofPeromyscus

Summary Three subspecies ofPeromyscus inhabiting the montane, foothill, and coastal plain regions of the Carolinas were trapped in midwinter and the occurrence of spontaneous and ration-induced daily torpor was monitored via biotelemetric determination of body temperature. All tests were undertaken with field-caught mice that were subjected to a minimum of laboratory acclimation (two days). The tendency to enter torpor in the presence of adequate food was highest inP. maniculatus nubiterrae, whose natural montane habitat presents it with the greatest seasonal stress in terms of ambient temperature and food availability. This species exhibited significantly (P<0.05) longer spontaneous torpor bouts than did the two lowland subspecies,P. gossypinus gossypinus andP. leucopus leucopus (Table 1). Restriction of food to one-half thead libitum level increased the frequency, duration, and depth (mean minimum body temperature) of torpor in all three species (Fig. 1).P. maniculatus, however, displayed significantly (P<0.001) longer episodes of torpor induced by rationing than did either of the other two subspecies. The ability to compensate for a reduction in energy intake by adjusting levels of energy utilization may profoundly affect survival during short-term environmental stress in any of these three species.