Answer questions for the abstract

Causes and consequences of genetic conflicts

Conflict is pervasive in biology, and even occurs at the genetic level. For example, host-virus interactions often play out as conflict between host immune genes and viral genes that antagonize them. Such genetic conflicts often escalate into evolutionary ‘arms races’. We study the causes and functional consequences of genetic conflicts to gain insights into evolution as well as disease mechanisms.

Host-virus conflict

The ability of host cells to sense viruses is critical to successfully fight off viral infections. Host protein MAVS plays a central role in sensing infection by RNA viruses. Interestingly, many viruses have evolved ways to antagonize MAVS as a way to evade detection by the host. Our phylogenetic analyses show that MAVS has recurrently and rapidly evolved in primates, indicating that it has been engaged in an arms race with viral antagonists throughout primate history.

Hepatitis C virus, which infects almost 200 million people worldwide and causes liver disease, is one such virus that antagonizes MAVS protein. Interestingly, based on functional experimentation, we found that MAVS from multiple primate species have independently acquired adaptive amino acid changes that protect it from HCV antagonism. Remarkably, most of these changes occur at the same single residue. Thus, multiple primate species have independently converged on the same strategy to escape from HCV antagonism.

Conflict between mtDNA and nuclear genome

While it is easy to recognize the conflict of interest between host and viruses, conflict can also occur between genomes within the same cell. Mitochondria possess their own genome (mtDNA), which is exclusively transmitted through females. This uniparental inheritance renders natural selection ineffective at removing mtDNA mutations that are deleterious to males but neutral or beneficial in females. While the male-harming effects of mutations in mtDNA are of little consequence for its own evolutionary success, they are clearly detrimental for the long-term evolutionary survival of the nuclear genome, which requires males to be healthy. Thus, the nuclear genome is predicted to encode suppressors that restore decreases in male fitness caused by mutations in mtDNA. Thus, analogous to host-virus interaction, a back and forth arms race is predicted to ensue between mtDNA and the nuclear genome. We utilized a novel experimental evolution strategy in Drosophila melanogaster to study male-harming mtDNA mutations and their suppression by the nuclear genome. We recovered a single mutation in mtDNA that specifically causes an age-dependent decrease in male fertility. Cell biological analyses of sperm development indicate defects in sperm cell maturation. Interestingly, the nuclear genomes from a number of wild isolates are able to suppress the male fertility defect caused by the this mutation. Taken together, our study reveal the cellular and molecular dynamics and disease consequences of the evolutionary arms race between mtDNA and the nuclear genome.

From the Abstract Answer the following questions .

1. What unknown question is the scientist/author addressing or attempting to answer and or understand?

2. From reading the abstract, what do you propose the hypothesis to be?

3. What model was used?

4. Give at least one outcome or result of the study.

5. Name one experimental tool that was used to achieve the above outcome.

6. What is the importance of the study?

7. Does this study provide any broader impact for mankind? Why or why not?

8. What protein(s) or cell type is (are) the target(s) of this study? What other protein or cell type might be used to address the problem?