This work continues our investigations into the role of gene conversion in the evolution of mammalian gene families. For the past five years our studies of the organization and evolution of the mouse alpha and beta-globin genes have documented how the exchange of genetic information between members of these gene families preserves overall sequence similarity while simultaneously shuffling markers so as to assemble new combinations of mutations. We now propose a novel analytical approach to the study of recombination in the mammalian genome. We have devised a technique to analyze gene conversion and related events in the germ line of the mouse with great sensitivity. The approach hinges on the ability to score DNA molecules carried by individual gametes. It has two elements: transgenic tester mice and a Haemophilus-based assay for gene conversion. The first element is the construction of strains of tester mice with integrated """"""""indicator"""""""" segments of DNA containing Haemophilus sequences. In the mouse genome, these indicators serve as potential substrates for gene conversion, and such events will result in a selectable phenotype in Haemophilus. The second element is the use of the exquisitely selective Haemophilus transformation system with which competent bacterial cells can take up and express the """"""""indicator"""""""" sequences from unfractionated gametic DNA with near 100% efficiency. The technique is sensitive enough allow the detection of gene conversion events with a frequency as low as 10-6 in the gametes of a single tester mouse.
| Erhart, M A; Piller, K; Weaver, S (1987) Polymorphism and gene conversion in mouse alpha-globin haplotypes. Genetics 115:511-9 |
| Holdener-Kenny, B; Weaver, S (1986) A naturally occurring deletion in the mouse Hbbs beta-globin gene cluster. Proc Natl Acad Sci U S A 83:4374-8 |
| Shyman, S; Weaver, S (1985) Chromosomal rearrangements associated with LINE elements in the mouse genome. Nucleic Acids Res 13:5085-93 |
| Erhart, M A; Simons, K S; Weaver, S (1985) Evolution of the mouse beta-globin genes: a recent gene conversion in the Hbbs haplotype. Mol Biol Evol 2:304-20 |
