236W Poster - Population Genetics
Wednesday June 08, 8:30 PM - 9:15 PM

Authors:
Sarah Marion ¹; Brenda Manzano-Winkler ¹; Hannah John ²; Iman Hamid ¹; Mohamed Noor ¹

Affiliations:
1) Duke University, Durham, NC; 2) National Resilience, Inc., Durham, NC

Keywords:
Natural selection

For nearly a century, evolutionary biologists have observed chromosomes which cause lethality when made homozygous persisting at surprisingly high frequencies (>25%) in natural populations of many species. These curious findings provide a challenging question fundamental to understanding natural fitness variation: given the extreme deleterious nature of lethal mutations, why do they appear at such high frequencies? Although most research on this question dates to the 1930’s, we still know remarkably little about the genetic basis of naturally occurring lethal mutations or what evolutionary forces create their frequencies. Before even attempting to explain why lethal alleles (lethals) are so common in nature, it is crucial to understand their genetic underpinnings. Decades of research has assumed lethal chromosomes are due to single locus, loss-of-function mutations, but this has never been directly tested. Even less is known about the classes of genes in which lethal mutations occur or their distribution throughout the genome.
We are using wild Drosophila melanogaster to determine the genetic basis of lethal mutations. D. melanogaster were collected from a natural population in Durham, North Carolina, and balancers were used to isolate ~300 independent samples in which chromosome 2 is homozygous lethal. We are in the process of crossing deficiency lines that span over 70% of the second chromosome to map lesions in all lethal isolines as a novel demonstration that most lethal alleles are single-locus and result in loss of function. Fine scale mapping and sequencing results provide novel characterization of naturally occurring lethals, including a nonsense mutation in the drosha gene. While this provides evidence that at least some lethal alleles are single locus, we also provide novel evidence that most or all lethal alleles are single locus using Poisson-based mapping expectations.
We present the most extensive mapping study of naturally occurring lethal alleles ever conducted. Our results are the first direct demonstration for a single locus, loss-of-function mode of action of lethal mutations and provide sequence-level characterization of naturally occurring lethal alleles.