Abstract

Many primate genes produce circular RNAs (circRNAs). However, the extent of circRNA conservation between closely related species remains unclear. By comparing tissue-specific transcriptomes across over 70 million years of primate evolution, we identify that within 3 million years circRNA expression profiles diverged such that they are more related to species identity than organ type. However, our analysis also revealed a subset of circRNAs with conserved neural expression across tens of millions of years of evolution. By comparing to species-specific circRNAs, we identified that the downstream intron of the conserved circRNAs display a dramatic lengthening during evolution due to the insertion of novel retrotransposons. Our work provides comparative analyses of the mechanisms promoting circRNAs to generate increased transcriptomic complexity in primates.

Highlights

  • An important question in biology is how has the complexity of biological systems expanded while the number of protein-coding genes has remained mostly stable

  • Our approach is unique as it focuses on the conservation of circRNAs in very closely related species enabling us to account for the rapid evolution of these RNAs

  • We identify a core set of over circRNA that are conserved across millions of years of evolution

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Summary

Introduction

An important question in biology is how has the complexity of biological systems expanded while the number of protein-coding genes has remained mostly stable. Back-splicing occurs co- and post- transcriptionally and is facilitated by inverted repeat elements that promote complementarity between adjacent introns favouring circRNA formation over linear splicing (Jeck et al, 2013; Liang and Wilusz, 2014; Ivanov et al, 2015; Zhang et al, 2014). The production of circRNAs can arise due to the perturbed expression of trans-factors and the inhibition of the core splicing machinery (Aktaş et al, 2017; Liang et al, 2017) These spuriously produced circRNAs are maintained as their circular shape protects them from the activity of cellular exonucleases (Gokool et al, 2020b). Our results identify evidence of circRNA conservation within closely related species and identify a reoccurring mechanism that correlates with circRNA genesis facilitating the expansion of transcriptomic complexity of primate cells

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