Colloquium - "GFolding and Replication of RNAs in the RNA World ", Paul G Higgs
Dr Paul G Higgs
Dept of Physics and Astronomy
McMaster University, Hamilton, Ontario.
Title: Folding and Replication of RNAs in the RNA World
Abstract: According to the RNA World theory for the origin of life, the first replicating molecules were nucleic acids that had the ability to act as both a gene and a catalyst. I will use RNA folding algorithms to ask how rare are sequences that form functional structures, and evolutionary models to ask how accurate does RNA replication have to be in order to maintain a functional sequence and structure.
(1) The survival of replicating RNAs depends on a mechanism that promotes cooperation - either spatial clustering in surface models or group selection in protocell models. We are interested in determining the error threshold in both these cases - i.e. the maximum error rate that can be sustained.
(2) The C base in RNA is chemically unstable and may not have been present on the early Earth. We therefore ask whether an RNA world could function with only a three-letter AUG alphabet. We show that AUG sequences can fold to a wide variety of secondary structures, suggesting that they could be functional catalysts; however replication is difficult in a three letter alphabet because sequences containing G have a very low fidelity. We conclude that G can play only a limited role in the RNA world if C is not present.
(3) RNA replication occurs via alternating plus and minus strands. It is usually assumed that only one of these strands is functional. However, there is a selective advantage of dual-folding sequences where the same functional structure is formed by both strands. We find that dual folding sequences are rare, unless the structure is very simple or unusually symmetric. The dual-folding sequences are viable evolutionarily, but only in cases where they are sufficiently common. Otherwise they are unlikely to be formed in the first place.
Refreshments will be available at 3:00 pm in HH/216