The house mouse is the source of almost all genetic variation in laboratory mice; its genome was sequenced alongside that of humans, and it has become the model for mammalian speciation. Featuring contributions from leaders in the field, this volume provides the evolutionary context necessary to interpret these patterns and processes in the age of genomics. The topics reviewed include mouse phylogeny, phylogeography, origins of commensalism, adaptation, and dynamics of secondary contacts between subspecies. Explorations of mouse behaviour cover the nature of chemical and ultrasonic signalling, recognition, and social environment. The importance of the mouse as an evolutionary model is highlighted in reviews of the first described example of meiotic drive (t-haplotype) and the first identified mammalian speciation gene (Prdm9). This detailed overview of house mouse evolution is a valuable resource for researchers of mouse biology as well as those interested in mouse genetics, evolutionary biology, behaviour, parasitology, and archaeozoology.
Mus domesticus and Mus musculus are two species of house mice which have evolutionarily diverged and recently come into contact again. These species are closely related enough to interbreed (hybridize) resulting in gene flow between the two species. This secondary contact has occurred in Europe, resulting in a hybrid zone stretching north to south across the continent. The t-haplotype is a gene complex in Mus species causing non-Mendelian inheritance, transmitting to the next generation at an unusually high rate. This unusual genetic element has been studied in natural populations but has received little attention in the M. domesticus -- M. musculus hybrid system. A Polymerase Chain Reaction (PCR) based assay was used to investigate the distribution of the t-haplotype in the Saxony transect of the M. domesticus -- M. musculus hybrid zone. Sequences from the Sanger Institute's Mouse Genomes project were used to investigate rates of gene evolution in the t-complex and in highly introgressing genomic regions. The t-haplotype was found to not cross the hybrid zone readily. Complete t-haplotypes were only found in the M. domesticus side of the hybrid zone, with one partial t-haplotype in the M. musculus side. The t-complex contains multiple rapidly evolving genes which likely contributed to the evolution of transmission ratio distortion and may contribute to reproductive isolation. Highly introgressing genomic regions were found to be evolving more slowly, introgressing due to neutral forces or weak positive selection. This study illustrates the interplay between gene flow and molecular evolution in the M. domesticus -- M. musculus hybrid zone.
Understanding the genetic basis of morphological evolution in nature is an area of study that still eludes evolutionary biologists. Islands are natural laboratories with distinct differences in habitat from the mainland, facilitating repeated cases of rapid morphological evolution of colonizing populations. Many examples of evolution on islands involve the vertebrate skeleton, particularly in the house mouse Mus musculus domesticus. Although the genetic basis of skeletal variation has been studied in laboratory strains of house mice, the genetic determinants of skeletal evolution in nature remain poorly understood. This thesis investigates skeletal evolution in a population of giant house mice from Gough Island. Focusing on an island population from the same subspecies as the laboratory mouse allows for the identification of genetic loci associated with skeletal evolution using quantitative genetic techniques. Through quantitative trait locus (QTL) mapping, it was discovered that pronounced changes in the size of the Gough Island mouse skeleton evolved through a few genetic loci acting in pleiotropy with global effects on growth. Gough Island mice exhibit an elongation of the skull, prompting the characterization of mandible morphology and jaw performance in Gough Island mice. Geometric morphometric and quantitative genetic techniques were used to investigate the genetic basis and functional morphology of mandibular evolution in Gough Island mice. Size and shape changes of the Gough Island mouse mandible are pronounced. This includes the expansion and narrowing of the mandible, along with the widening of the condyle. The size and shape dimensions are controlled by distinct sets of loci. Regions of the mandible also show differences in their genetic architectures, suggesting that aspects of the evolution of mandible morphology in Gough Island mice are modular. This work highlights the importance of utilizing island populations in order to obtain a better understanding of complex trait evolution in a natural context.
Rodent Societies synthesizes and integrates the current state of knowledge about the social behavior of rodents, providing ecological and evolutionary contexts for understanding their societies and highlighting emerging conservation and management strategies to preserve them. It begins with a summary of the evolution, phylogeny, and biogeography of social and nonsocial rodents, providing a historical basis for comparative analyses. Subsequent sections focus on group-living rodents and characterize their reproductive behaviors, life histories and population ecology, genetics, neuroendocrine mechanisms, behavioral development, cognitive processes, communication mechanisms, cooperative and uncooperative behaviors, antipredator strategies, comparative socioecology, diseases, and conservation. Using the highly diverse and well-studied Rodentia as model systems to integrate a variety of research approaches and evolutionary theory into a unifying framework, Rodent Societies will appeal to a wide range of disciplines, both as a compendium of current research and as a stimulus for future collaborative and interdisciplinary investigations.
Details the diversity, evolution and ecology of this much neglected group of animals, and describes their range of reproductive strategies and dietary adaptations. The book includes a chapter on rodent diseases, the impact of human settlement, and the efforts that are being made to conserve key species.
Determining the genetic basis of reproductive isolation is a fundamental goal in evolutionary biology. Intrinsic reproductive isolation often arises due to epistasis between divergent interacting genes. The rapid evolution of hybrid male sterility is known to have several causes, including the exposure of recessive X-linked incompatibilities in males and the rapid evolution of male reproductive traits. Despite these insights, little is known about the genetics of reproductive isolation during the early stages of speciation. This deficiency inspired parallel studies on the molecular evolution of male reproduction in house mice and the genetic basis of hybrid male sterility between two mouse species, Mus domesticus and M. musculus. Evolutionary analysis of 946 genes showed that the intensity of positive selection varies across sperm development and acts primarily on phenotypes that develop late in spermatogenesis (Appendix A). Several reciprocal crosses between wild-derived strains of M. musculus and M. domesticus were used to examine F1 hybrid male sterility (Appendix B). These crosses revealed hybrid male sterility linked to the M. musculus X chromosome and a novel sterility polymorphism within M. musculus. A large introgression experiment was used to further dissect the genetic basis of X-linked incompatibilities between M. musculus and M. domesticus (Appendix C). Introgression of the M. musculus X chromosome into a M. domesticus genetic background produced male sterility and involved a minimum of four factors. No sterility factors were uncovered on the M. domesticus X chromosome. These data demonstrate the complex genetic basis of hybrid sterility in mice and provide numerous X-linked candidate sterility genes. The molecular evolution of five rapidly evolving candidate genes was examined using population and phylogenetic sampling in Mus (Appendix D). Four of these loci showed evidence of positive natural selection. One locus, 4933436I01Rik, showed divergent protein evolution between M. domesticus and M. musculus and was one of a handful of testis-expressed genes within a narrow interval involved in hybrid male sterility. In summary, these data demonstrate that hybrid male sterility has a complex genetic basis between two closely related species of house mice and provide a foundation for the identification of specific mutations that isolate these species.
The Mouse in Biomedical Research, Volume I: History, Genetics, and Wild Mice focuses on the utility of the mouse as a laboratory animal in biomedical research. A historical perspective on the development and origins of the laboratory and wild mouse is given. The diversity of inbred strains of mice as well as the methods of developing and the genetic monitoring and testing of these strains are discussed. This volume consists of 14 chapters and begins with an overview of mice of the genus Mus and problems concerning evolution within the genus. The following chapters focus on taxonomy, nomenclature, and breeding systems, together with recombinant inbred and congenic resistant mouse strains. Methods of constructing, testing, and monitoring strains are described. Congenic strains, gene mapping, cytogenetics, and murine experimental studies are also considered, along with the histocompatibility-2 complex and radiation genetics. The final chapter is devoted to the pharmacogenetics of the laboratory mouse, paying particular attention to intoxication and detoxication pathways, genetically determined differences in xenobiotic metabolism, and pharmacogenetic polymorphisms. This book will be a useful reference for investigators using mice in many areas of research.
History, Wild Mice, and Genetics, the first volume in the four volume set, The Mouse in Biomedical Research, provides information about the history, biology and genomics of the laboratory mouse (Mus musculus), as well as basic information on maintenance and use of mouse stocks. Mouse origins and relationships are covered in chapters on history, evolutionary taxonomy and wild mice. Genetics and genomics of the mouse are covered in chapters on genetic nomenclature, gene mapping, cytogenetics and the molecular organization of the mouse genome. Maintenance of laboratory mice is described in chapters on breeding systems for various types of strains and stocks and genetic monitoring. Use of the mouse as a model system for basic biomedical research is described in chapters on chemical mutagenesis, gene trapping, pharmacogenetics and embryo manipulation. The information in Volume 1 serves as a primer for scientists new to the field of mouse research.
Whole-genome studies of rates of protein evolution show that genes underlying reproduction and immunity tend to evolve faster than other genes, consistent with the frequent action of positive selection. The evolution of immunity has been well-studied at the interspecific level, but much remains unknown about the population-level dynamics of immunity. This project described genetic variation at immunity and non-immunity loci as well as variation among levels of infection for diverse pathogens in a natural population of mice from Tucson. Analysis of autosomal and X-linked loci in the native range ofMus domesticus, the species from which Tucson mice are primarily descended, revealed low levels of variation consistent with a recent population expansion, resulting in a slight excess of rare alleles across the genome. Genetic variation among a set of classical inbred strains represented a small fraction of wild variation. An overlapping set of genes sequenced in mice from Tucson revealed that there is significant introgression fromMus castaneus. After controlling for gene flow, Tucson mice showed evidence of a mild bottleneck that produced a slight excess of intermediate frequency alleles, but did not result in a dramatic loss of genetic variability. Most of the 15 pathogens and parasites studied in Tucson were found at low to intermediate frequency, and most mice had one to three infections, suggesting that there are many opportunities for host-pathogen coevolution, and a possible role for coinfection. A study ofFv-4, which confers resistance to murine leukemia viruses, confirmed that the resistance allele originated inM. castaneusand is now found at intermediate frequency in Tucson after introduction through gene flow. Finally, a study of the recently duplicatedCeacam1andCeacam2genes, previously shown to be involved in resistance to mouse hepatitis virus (MHV), revealed that a gene conversion event moved a suite of mutations fromCeacam2toCeacam1. An elevated rate of protein evolution showed thatCeacam2had experienced positive selection after duplication. Interestingly, there was no association between MHV antibody presence andCeacam1genotype in Tucson. This project showed that gene flow and gene conversion mediated resistance to infections in wild mice.