EVOLUTIONARY HISTORY OF THE MOUSE T COMPLEX--A MOLECULAR GENETICS APPROACH

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The region of mouse Chromosome 17 (Char 17) known as the t complex offers a model system in which important questions about mammalian genome organization and evolution can be addressed. The t complex is a naturally occurring chromosome variant that is found in virtually all populations of mice belong to the Mus musculus group. The field of mammalian genetics as a whole, and human genetics in particular, greatly benefit from the work on the t complex. The t complex is inherently fascinating not only because it is home to genes that influence important processes (sperm development, fertilization, embryonic viability, development of the vertebral column, and a number of mouse behaviors, such as male aggression and female mate choice) but because it also provides a model system for genome analysis-specifically the relationship between genome sequences and gene function. We will use comparative DNA sequence analysis of selected clones from two loci as a means of contemplating the picture of the origin of the t complex. We have developed a comparative DNA sequence analysis of selected clones from two loci as a means of completing the picture of the origin of the t complex. Using an oligonucleotide screening method that has allowed us to identify genomic clones from a discrete segment of Chr 17, we hope to characterize novel portions of the t complex orthologous region of Mus spretus. Another resource developed by us, a series of mouse lines congenic for discrete and overlapping segments of the proximal portion of Chr 17 will allow genetic tests for particular gene functions. Finally, the influence of the t complex on mouse behavior will be examined, by laboratory testing of the congenic mice for male aggression and female mate choice. These experiments may eventually result in the cloning of the genes responsible for these traits. An important potential outcome of this work is the application of lessons learned from studying the mouse t complex to the Human Genome Project: namely, that even when a genomic segment is subjected to exhaustive genetic analysis or DNA sequence analysis, structure-function relationships often remain elusive, requiring novel approaches in order to uncover these relationships.