Ashley Wiltsie, University of Utah
The central dogma of biological processes is the conversion of information stored in DNA into proteins, through the mechanisms of transcription and translation. For the proper functioning and survival of an organism, these processes must be performed with great fidelity. Nonsense-mediated mRNA decay (NMD) is a process occurring in conjunction with translation that surveilles mRNAs containing nonsense mutations, also called premature termination codons (PTCs), and causes their rapid degradation. In the absence of NMD, mRNAs containing nonsense mutations are translated into truncated proteins. In this way, the cell prevents the translation of truncated proteins, which can lead to lethality within the organism due to misfolding or the buildup of unusable proteins lacking critical domains. To assess how the loss of NMD affects the viability of individuals carrying naturally occurring genetic variants in this experiment, we crossed Drosophila melanogaster (fruit fly) mutants that lack NMD pathway function to a series of lines that contain naturally occurring variants. The source of these variants is the well characterized Drosophila Genome Reference Panel (DGRP). Of the 168 DGRP lines tested, we discovered that 11 lines showed significant viability difference when NMD is inactivated. Of these 11 lines, 9 showed a significantly decreased viability, while the other 2 lines demonstrated a significantly increased viability. Our major conclusion is that the majority of naturally occurring variants have no significant influence on the viability of the fly when NMD is absent. However, a small number of variants do produce a strong effect on viability, presumably because they are detrimental to the organism if not broken down by the NMD pathway.