A mitochondrial DNA hypomorph of cytochrome oxidase specifically impairs male fertility in Drosophila melanogaster

Cell compartments called mitochondria are responsible for producing much of the energy that animal and plant cells need. Most of the proteins in mitochondria are produced from genes found in another compartment called the nucleus. However, some mitochondrial proteins are made from genes found in the mitochondria themselves. Unlike the genes in the nucleus, which animals and plants inherit from both their mother and father, the mitochondrial “genome” is only passed on along the female line. Therefore, males represent an evolutionary dead-end for mitochondrial genes. Evolutionary theory predicts that this should result in the evolution and spread of mutations that can be harmful to males, providing they do not reduce the ability of females to survive and reproduce. Although such ‘male-harming’ mutations have been well studied in plants, it is less clear how common they are in animals. Patel, Miriyala, Littleton et al. used fruit flies as a model system to identify and characterize male-harming mutations in the mitochondrial genome. The experiments isolated a mitochondrial genome with a single mutation in a gene that encodes an enzyme called cytochrome oxidase II. The mutation is said to be “hypomorphic” because it lowers the activity of the gene. The fertility of male flies with this mutation rapidly declined as they aged. However, the mutation did not appear to lower the fertility of female flies. In fact, apart from the lower male fertility, the mitochondrial mutation did not seem to affect any other traits in males or females. Further experiments revealed that this hypomorphic mutation specifically impairs the development of sperm. Patel, Miriyala, Littleton et al. also found that the effect of the mutation on the fertility of the males depended on the genes in the nucleus of their cells, as some nuclear genomes were able to partially or completely suppress the mutation. This supports previous findings that the effect of mitochondrial mutations in animals and plants may be complex and can be strongly influenced by the genes in their nucleus. Patel, Miriyala, Littleton et al.’s findings suggest that sperm development is particularly susceptible to defects in mitochondria, and that hypomorphic mutations may represent a broader category of ‘male-harming’ mutations in animals. A future challenge will be to find out whether such mutations occur in humans and whether they are associated with infertility in men.