Affiliation:
1. Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, Helsinki FI-000, Finland
Abstract
The mechanisms generating novel genes and genetic information are poorly known, even for microRNA (miRNA) genes with an extremely constrained design. All miRNA primary transcripts need to fold into a stem-loop structure to yield short gene products (
∼
22 nt) that bind and repress their mRNA targets. While a substantial number of miRNA genes are ancient and highly conserved, short secondary structures coding for entirely novel miRNA genes have been shown to emerge in a lineage-specific manner. Template switching is a DNA-replication-related mutation mechanism that can introduce complex changes and generate perfect base pairing for entire hairpin structures in a single event. Here, we show that the template-switching mutations (TSMs) have participated in the emergence of over 6,000 suitable hairpin structures in the primate lineage to yield at least 18 new human miRNA genes, that is 26% of the miRNAs inferred to have arisen since the origin of primates. While the mechanism appears random, the TSM-generated miRNAs are enriched in introns where they can be expressed with their host genes. The high frequency of TSM events provides raw material for evolution. Being orders of magnitude faster than other mechanisms proposed for de novo creation of genes, TSM-generated miRNAs enable near-instant rewiring of genetic information and rapid adaptation to changing environments.
Publisher
Proceedings of the National Academy of Sciences
Cited by
1 articles.
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