CAREER: The Limits of Mendelian Genetics: Sperm Influences Female Meiotic Segregation

University Of North Carolina At Chapel Hill, Chapel Hill NC

Investigators

Abstract

Males from several laboratory inbred strains produce a sperm factor that is able to interact with the female meiotic spindle apparatus at the second meiotic division, disrupting the random segregation of chromatids between the zygote and the second polar body. On the other hand, the male sperm from other inbred strains do not interfere with the expected random segregation of chromatids. In hybrid males generated by crossing animals from these two types of inbred strains, the phenotype appears to segregate as a single locus that is expressed at the haploid stage of spermatogenesis. The objective of the project is to characterize this unusual effect of the sperm in nonrandom segregation of maternal alleles during female meiosis. This research project has two aims: i) characterize the mode of inheritance of the sperm factor and ii) identify the molecular nature of the gene, or genes, responsible for this phenotype using a combination of positional cloning, comparative genomics methods and functional assays. The characterization of true exceptions to Mendel's laws of inheritance has been a highly successful approach in uncovering general principles in genetics. The phenotype to be studied in this project, nonrandom segregation of chromatids during female meiosis that is driven by the genotype of the fertilizing sperm, represents a true violation to Mendel's law of segregation. In addition, it also violates the basic assumption of Mendelian genetics that the segregation of alleles during meiosis in one sex is independent from the segregation of alleles in the other sex, i. e., the inheritance of genetic information from one parent is independent of the inheritance of genetic information from the other parent. The information gathered in this research has great potential to provide new insights in the mechanisms of control of chromosome segregation during meiosis and to refine the standard models commonly used in the fields of genetics and evolutionary biology. In the past decade a trend has become apparent in the curricula of genetics at graduate and undergraduate levels. An increasing emphasis has been placed in the molecular aspects of gene action and gene regulation, while basic aspects of transmission genetics are briefly summarized and often presented as a complete body of knowledge. Although one may argue that this approach has been exceedingly successful in the characterization of the molecular basis of disease, it is also clear that some observations violate the most basic assumptions of Mendelian Genetics. These observations reject the commonly held opinion that transmission genetics was essentially solved in the past century and exemplifies the open-ended nature of the quest to fully understand the principles and mechanisms governing the transmission of genetics information. The underlying rationale of this research project (i. e., testing the validity of basic assumptions of genetic models) and the results generated have a great educational significance that will be integrated within course design, teaching and supervision at the high school, undergraduate, graduate and postdoctoral levels.