The Evolution of the Viral RNA Sensor OAS1 in Old World Monkeys and Cetartiodactyls

<p>Animals produce an array of sensors patrolling the intracellular environment poised to detect and respond to viral infection. The oligoadenylate synthetase family of enzymes comprises a crucial part of this innate immune response, directly signaling endonuclease activity responsible for inhibiting viral replication. Oligoadenylate synthetase 1 plays a vital role in animal susceptibility to pathogens including flaviviruses such as dengue, West Nile, and hepatitis c virus. This thesis includes a population level analysis of OAS1 diversity within macaque and baboon species followed by a broader survey of the gene in nineteen Old World monkeys. My research found that at the species level, macaques exhibit extremely high diversity with intriguing similarities to that previously found in chimpanzees. Across Old World monkeys, I identified commonly shared patterns of positive selection. Detailed structural analysis of OAS1 variation indicates sites of accelerated evolution at the host-virus interface and at sites of possible viral antagonism, both signifying a history of virus-driven evolution. Finally, I have analyzed the cetartiodactyl OAS1 gene family which includes two, and in some lineages, three copies of OAS1. This analysis identifies some of the same regions under evolutionary pressure as found in primates and also highlights others suggesting neofunctionalization of paralogous genes.</p>

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Biology

Grantor

The Graduate School and University Center of The City University of New York

Year dc:date.available

2016

Author dc:creator

• Fish, Ian

Advisors dc:contributor.advisor

• Stéphane Boissinot
• Cathy Savage-Dunn

Committee members dc:contributor.committeemember

• Cathy Savage-Dunn
• Susan Rotenberg
• Shaneen Singh
• Margaret MacDonald

• Evolution
• Molecular Biology
• Molecular Genetics
• OAS1
• Oligoadenylate Synthetase 1
• antiviral sensor
• innate immunity
• immune evolution

Repository record dc:identifier

https://academicworks.cuny.edu/gc_etds/759

OAI identifier oai:identifier

oai:academicworks.cuny.edu:gc_etds-1752