PT - JOURNAL ARTICLE AU - Kamaludin Dingle AU - Fatme Ghaddar AU - Petr Šulc AU - Ard A. Louis TI - Phenotype bias determines how RNA structures occupy the morphospace of all possible shapes AID - 10.1101/2020.12.03.410605 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.12.03.410605 4099 - http://biorxiv.org/content/early/2020/12/03/2020.12.03.410605.short 4100 - http://biorxiv.org/content/early/2020/12/03/2020.12.03.410605.full AB - The relative prominence of developmental bias versus natural selection is a long standing controversy in evolutionary biology. Here we demonstrate quantitatively that developmental bias is the primary explanation for the occupation of the morphospace of RNA secondary structure (SS) shapes. By using the RNAshapes method to define coarse-grained SS classes, we can directly measure the frequencies that non-coding RNA SS shapes appear in nature. Our main findings are, firstly, that only the most frequent structures appear in nature: The vast majority of possible structures in the morphospace have not yet been explored. Secondly, and perhaps more surprisingly, these frequencies are accurately predicted by the likelihood that structures appear upon uniform random sampling of sequences. The ultimate cause of these patterns is not natural selection, but rather strong phenotype bias in the RNA genotype-phenotype (GP) map, a type of developmental bias that tightly constrains evolutionary dynamics to only act within a reduced subset of structures which are easy to “find”.Competing Interest StatementThe authors have declared no competing interest.