Identification and characterization of genes potentially involved in meiosis in Drosophila melanogaster males

Author

Wendy Bradberry Stapleton

Date of Award

8-1999

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

Bruce D. McKee

Committee Members

Jeffery Becker, Ranjan Ganguly, Mary Ann Handel, Wesley Wicks

Abstract

The process of meiosis is an essential mechanism in sexually reproducing organisms that allows the reduction of the genome size in gametes so that formation of a zygote from an egg and sperm leads to progeny with the proper chromosome complement. Although studies of the meiotic process have allowed determination of the steps that occur to reduce the genome complement, identification of all the gene products involved is not yet complete. Important cellular pathways are often highly conserved during evolution. Therefore, it is helpful to gain an understanding of complicated processes by studying simple model organisms.Drosophila melanogaster is an ideal system for the genetic study of processes such as meiosis. A few of the many attributes of this organism are its well defined genetics, small genome size, and short generation time. Although numerous screens to obtain meiotic mutants have been performed over the last twenty-five years, there are still many gaps in our knowledge about gene products that function in the various meiotic pathways. Therefore, these studies represent additional attempts to identify factors involved in Drosophila meiosis. Although initial goals were to identify genes that function specifically in male meiosis, the nature of some of the factors obtained may lead into a study of the meiotic process in general, involving both male and female pathways.Our search for Drosophila meiotic mutations has identified four genes that potentially act in meiosis. homeless is a gene initially identified by its female sterile phenotype and its role in oogenesis has been characterized. This study reports the finding that Homeless is also important in spermatogenesis. Phenotypic characteristics of mutant flies resemble those previously characterized in Suppressor of Stellate(Su(Ste)^-) and XO males, suggesting that at least one of its meiotic functions is torepress the testis specific Stellate locus. An additional factor, identified by observation of abnormal sex chromosome segregation in a deficiency stock, appears to affect both male and female meiosis. nondisjunction in males and females (nmf) causes chromosome nondisjunction in bothsexes. The phenotypic characteristics of the mutation suggest the gene may be normally involved in segregation of achiasmate chromosomes in the male and female meiotic process. However, studies have not yet confirmed that both the male and female phenotypes are due to the same gene locus.Gene products acting in cellular processes in an organism can often be obtained by identifying homologs of proteins known to function in that process in another organism. Homologs of proteins involved in mismatch repair in bacteria have been shown to have additional meiotic functions in yeast, mice, and potentially humans. Wehave identified two Drosophila homologs of the bacterial mismatch repair genes mutL,hexB, and yeast Pmsl. Initial characterization supports meiotic roles for dmlh1 and dpms2, but identification and study of mutations in these genes is necessary to confirm participation of their products in meiosis.