Overlapped genes resolve evolutionary conflict by a selfish segregation of functional motifs

Speaker Name: 
Jason Fernandes
Speaker Organization: 
University of California, San Francisco
Start Time: 
Thursday, September 3, 2015 - 11:15am
End Time: 
Thursday, September 3, 2015 - 12:15pm
599 Engineering 2
David Haussler

Abstract: The advent of genomic sequencing revealed that genes can share coding overlap. This genetic arrangement poses an evolutionary dilemma as one region of DNA must evolve under the joint selection pressures of multiple proteins. The essential viral regulatory genes tat and rev of HIV-1 provide an ideal system to explore this problem as both are subject to strong selective forces. Here we combine analyses of patient sequences, complete functional alanine scanning, and directed evolution experiments using all 12,928 point mutants in engineered, non-overlapped viruses. We find that the selfish organization of the tat/rev overlap, in which nucleotides are dedicated to one gene or the other but never both, minimizes the constraining effects of overlap.

Additionally, we discover that the overlap provides evolutionary advantages by excluding deleterious genotypes. This analysis forms the first comprehensive dissection of an overlap, providing insight into general mechanisms by which evolution balances competing selective forces.