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Evolution of miRNA binding sites and regulatory networks in cichlids

View ORCID ProfileTarang K. Mehta, Luca Penso-Dolfin, Will Nash, Sushmita Roy, Federica Di-Palma, View ORCID ProfileWilfried Haerty
doi: https://doi.org/10.1101/2021.12.14.472604
Tarang K. Mehta
1Earlham Institute (EI), Norwich, UK
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  • For correspondence: Tarang.Mehta@earlham.ac.uk
Luca Penso-Dolfin
2Silence Therapeutics GmbH, Robert-Rössle-Straße 10, 13125 Berlin, Germany
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Will Nash
1Earlham Institute (EI), Norwich, UK
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Sushmita Roy
3Dept. of Biostatistics and Medical Informatics, UW Madison, Madison, USA
4Wisconsin Institute for Discovery (WID), Madison, USA
5Dept. of Computer Sciences, UW Madison, Madison, USA
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Federica Di-Palma
6School of Biological Sciences, University of East Anglia, Norwich, UK
7Genome British Columbia, Vancouver, Canada
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Wilfried Haerty
1Earlham Institute (EI), Norwich, UK
6School of Biological Sciences, University of East Anglia, Norwich, UK
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Abstract

The divergence of regulatory regions and gene regulatory network (GRN) rewiring is a key driver of cichlid phenotypic diversity. However, the contribution of miRNA binding site turnover has yet to be linked to GRN evolution across cichlids. Here, we extend our previous studies by analysing the selective constraints driving evolution of miRNA and transcription factor (TF) binding sites of target genes, to infer instances of cichlid GRN rewiring associated with regulatory binding site turnover. Comparative analyses identified increased species-specific networks that are functionally associated to traits of cichlid phenotypic diversity. The evolutionary rewiring is associated with differential models of miRNA and TF binding site turnover, driven by a high proportion of fast-evolving polymorphic sites in adaptive trait genes compared to subsets of random genes. Positive selection acting upon discrete mutations in these regulatory regions is likely to be an important mechanism in rewiring GRNs in rapidly radiating cichlids. Regulatory variants of functionally associated miRNA and TF binding sites of visual opsin genes differentially segregate according to phylogeny and ecology of Lake Malawi species, identifying both rewired e.g. clade-specific and conserved network motifs of adaptive trait associated GRNs. Our approach revealed several novel candidate regulators, regulatory regions and three-node motifs across cichlid genomes with previously reported associations to known adaptive evolutionary traits.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 16, 2021.
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Evolution of miRNA binding sites and regulatory networks in cichlids
Tarang K. Mehta, Luca Penso-Dolfin, Will Nash, Sushmita Roy, Federica Di-Palma, Wilfried Haerty
bioRxiv 2021.12.14.472604; doi: https://doi.org/10.1101/2021.12.14.472604
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Evolution of miRNA binding sites and regulatory networks in cichlids
Tarang K. Mehta, Luca Penso-Dolfin, Will Nash, Sushmita Roy, Federica Di-Palma, Wilfried Haerty
bioRxiv 2021.12.14.472604; doi: https://doi.org/10.1101/2021.12.14.472604

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