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Replication of Genes in Rolling Circles / encoding functions in circular replicators at the origin of life

A MSc thesis which describes a theoretical model for gene replication on circular RNA under prebiotic conditions / The origin of life is one of the most captivating and difficult questions that science has yet to answer. Several different questions remain, including how genetic replication may have begun. Replication is a fundamental property of life that allows for evolution and the long-term survival of life. Non-enzymatic replication should have been present at the origin of life. The RNA world theory proposes that because it can act as both an enzyme and gene, RNA could have performed the function of a replicator at the origin of life. Abiotic chemistry for RNA nucleotides is known, as well as mechanisms for simple but random RNA sequence synthesis. However non-enzymatic replication of RNA sequences which might hold functions, has only achieved mild success. This is in no small part because of replication infidelity between RNA bases, and product inhibition during template directed replication. The rolling circle mechanism found in viroids and some RNA viruses, is a likely way to avoid these issues in the RNA World. Here we present a summary of key topics to origins of life and the RNA world, a deterministic model for rolling circle replication, followed by an original computational model for gene fixation in rolling circle replication. In these simulations we observe the dynamics of populations of protocells, each containing multiple copies of rolling circle RNAs that can replicate non-enzymatically. Selection for speed of replication tends to reduce circles to a minimum length. However, errors provide a natural doubling mechanism that creates strands multiple times the length of the minimal sequence. We show that if a beneficial gene appears in this new space, the longer sequence with the beneficial function can be selected, even though it replicates more slowly. This provides a route for the evolution of longer circles encoding multiple genes. / Thesis / Master of Science (MSc) / The origin of life is a topic that many people are inherently curious about. However, science is only just making progress towards an answer. The first organisms must have been able to replicate. Modern organisms use proteins, DNA, and RNA to do this, however it is unlikely these three molecules could have co-ordinated at the origin of life. A simpler model for replication uses only RNA, which can be both a gene and a catalyst. Here we propose some computational models which study RNA replication. These models simulates strands undergoing rolling circle replication, a method of replication some viruses use which has been suggested to be sustainable at the origin of life. We show that rolling circle replication can create long strands which can have new helpful sequences of RNA. This mechanism could have helped the first organisms achieve better replication and evolution, which is a key characteristic of life.

Identiferoai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/27816
Date January 2022
CreatorsRivera-Madrinan, Felipe
ContributorsHiggs, Paul, Physics and Astronomy
Source SetsMcMaster University
LanguageEnglish
Detected LanguageEnglish
TypeThesis

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