Genomics, Proteomics, Bioinformatics

Rolling Circles As A Means Of Encoding Genes In The RNA World

By Keith Cowing
Press Release
February 7, 2023
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Rolling Circles As A Means Of Encoding Genes In The RNA World
Mechanism of non-enzymatic rolling circle replication. Blue and green strands are complimentary plus and minus strands, each of which contains a ribozyme unit AZ and its complement za. After one circuit around the template, a double strand is created. After another circuit, a tail is produced. When the AZ motif is exposed in the tail, cleavage occurs, creating a linear strand that can circularize and begin the cycle anew. — Life

The rolling circle mechanism found in viroids and some RNA viruses is a likely way that replication could have begun in the RNA World.

Here, we consider simulations of populations of protocells, each containing multiple copies of rolling circle RNAs that can replicate non-enzymatically. The mechanism requires the presence of short self-cleaving ribozymes such as hammerheads, which can cleave and re-circularize RNA strands. A rolling circle must encode a hammerhead and the complement of a hammerhead, so that both plus and minus strands can cleave.

Thus, the minimal functional length is twice the length of the hammerhead sequence. Selection for speed of replication will tend to reduce circles to this minimum length. However, if sequence errors occur when copying the hammerhead sequence, this prevents cleavage at one point, but still allows cleavage on the next passage around the rolling circle.

Thus, there is a natural doubling mechanism that creates strands that are multiple times the length of the minimal sequence. This can provide space for the origin of new genes with beneficial functions. 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.

Felipe Rivera-Madrinan, Katherine Di Iorio and Paul G. Higgs

Rolling Circles as a Means of Encoding Genes in the RNA World, Life (open access)


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