Genetical research on wild populations of house mice provides insight into the structure and dynamics of those populations. Knowledge of the natural genetic variation will enhance understanding of the genome of the laboratory mouse, which is a model system for investigating the basis of many diseases. Such knowledge will contribute to understanding what makes house mouse populations so successful and to knowledge of the genetic basis of evolution. In this project, the researchers will determine the nucleotide sequences of genes on the mitochondrial chromosome (mtDNA). MtDNA is of use in evolutionary studies because it evolves more rapidly than nuclear DNA. The data obtained will be used to estimate the rate of mtDNA evolution in mice and to compare it with the rate already measured in humans and other animals. The theories will be tested that generation time is a key factor in molecular evolution and that rodents have evolved significantly faster than other creatures at the molecular level. The results will also be used to investigate further the genetic interactions in the European hybrid zone between Mus domesticus and Mus musculus mice and to determine evolutionary relationships among various rodents closely and distantly related to house mice, with emphasis on cases where anatomical and fossil data have led to inferences in conflict with the available molecular evidence. A new technique will be used to obtain the DNA sequences. Starting with the DNA in a tiny amount of tissue, the polymerase chain reaction is used to amplify specific segments of DNA up to a million-fold; the amplified product can then be sequenced directly. Because this method avoids the tedious steps of cloning and searching for the desired clone among thousands or millions of others, it makes possible obtaining DNA sequence data on a large scale. Routine surveys at the DNA sequence level of hundreds of animals captured and then released after collection of a drop of blood or a few hairs are now feasible. Furthermore, because the traces of modified DNA that abound in museum skins and other samples suffice as the starting material, the world's storehouse of specimens accumulated over a century or more is at last accessible to molecular genetic analysis.
