Swept under the rug: A systematic analysis of genetic background effects in Drosophila

Michigan State University, East Lansing MI

Investigators

Abstract

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). It is well known that mutations in a sequence of DNA can have profound physical (phenotypic) effects. However, it is less well appreciated that the phenotypic consequences of such mutations depend on more than just the changes in the DNA sequence of that gene. Although the changes in the DNA are important, their phenotypic consequences can be modified both by the environment and by the genetic make-up of the individual possessing the mutation. In other words, two individuals possessing exactly the same mutation may not show the same phenotype, given that they have experienced different environments, and that the remainders of their genomes may be quite different. The consequences of the differences between their genomes are known as "genetic background effects", and while well known among geneticists, they have rarely been the focus of scientific studies. In this project, a series of mutations in a set of Drosophila melanogaster genes will be used to address several outstanding questions pertaining to the effects of an organism's genetic background. First, the genetic modifiers contributing to genetic background effects will be mapped to determine how they contribute to other phenotypes. The second goal of this project is to understand how pervasive such genetic background effects are in other genetic analyses. Finally, technologies that allow for the simultaneous examination of the transcriptional activity of all of the genes in the genome will be used to compare and test models pertaining to the consequences and causes of genetic background effects and variation in the strength of the mutations under study. The results from this research should help to provide a framework for a broader understanding of the spectrum of effects for a given mutation, and for series of mutations within and between genes. The principal intellectual merit of this project is that it will provide a systematic analysis of the consequences of genetic background effects, and thus will address the importance of genetic background effects for genetic studies and analyses. If the planned work confirms the preliminary results, this research could change how genetics is taught and how genetic analyses are performed. In addition, graduate students working on the project will receive mentoring and training, thus developing technical analytical skills in genetics, genomics, and statistics. To help to correct public misconceptions pertaining to genetics, the principal investigator has initiated a "blog" for genetics education for the general public. The blog will focus on correcting the misconception that genes encode traits, rather than variants of genes (alleles) that influence phenotypes. In addition, using recent examples "translated" from the literature (genesgonewild.blogspot.com), the blog will also discuss conditional effects of mutations and alleles, and the context-dependence of these effects (context referring to environment and genetic background).