Phenotype loss is associated with widespread divergence of the gene regulatory landscape in evolution
Juliana G. Roscito, Katrin Sameith, Genis Parra, Bjoern E. Langer, Andreas Petzold, Claudia Moebius, Marc Bickle, Miguel Trefaut Rodrigues & Michael Hiller
Nature Communications volume 9, Article number: 4737 (2018)
Source/Fonte: Science
Abstract
Detecting the genomic changes underlying phenotypic changes between species is a main goal of evolutionary biology and genomics. Evolutionary theory predicts that changes in cis-regulatory elements are important for morphological changes. We combined genome sequencing, functional genomics and genome-wide comparative analyses to investigate regulatory elements in lineages that lost morphological traits. We first show that limb loss in snakes is associated with widespread divergence of limb regulatory elements. We next show that eye degeneration in subterranean mammals is associated with widespread divergence of eye regulatory elements. In both cases, sequence divergence results in an extensive loss of transcription factor binding sites. Importantly, diverged regulatory elements are associated with genes required for normal limb patterning or normal eye development and function, suggesting that regulatory divergence contributed to the loss of these phenotypes. Together, our results show that genome-wide decay of the phenotype-specific cis-regulatory landscape is a hallmark of lost morphological traits.
Acknowledgements
We thank the genomics community for sequencing and assembling the genomes of the many vertebrates used here, and the UCSC genome browser group for providing software and genome annotations. We also thank Virag Sharma for running CESAR, Nadine Vastenhouw for experimental infrastructure, Tiago Ferreira for helping with dissection of mouse eyes, Terence Capellini for helpful comments on the manuscript and on the experimental assay, Aliona Bogdanova for cloning of plasmids, Jared Simpson for help with SGA, and Andreas Dahl and Sylke Winkler for DNA sequencing, the Computer Service Facilities of the MPI-CBG and MPI-PKS, and the DNA Sequencing, Microarray and Biomedical service facilities of the MPI-CBG for their support. This work was supported by the Max Planck Society, and by FAPESP stipends 2012/01319-8 and 2012/23360 to J.G.R.
Author information
Author notes
These authors contributed equally: Juliana G. Roscito, Katrin Sameith, Genis Parra.
Affiliations
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, 01307, Germany
Juliana G. Roscito, Katrin Sameith, Genis Parra, Bjoern E. Langer, Claudia Moebius, Marc Bickle & Michael Hiller
Max Planck Institute for the Physics of Complex Systems, Dresden, 01187, Germany
Juliana G. Roscito, Katrin Sameith, Genis Parra, Bjoern E. Langer & Michael Hiller
Center for Systems Biology Dresden, Dresden, 01307, Germany
Juliana G. Roscito, Katrin Sameith, Genis Parra, Bjoern E. Langer & Michael Hiller
Instituto de Biociências, Universidade de São Paulo, São Paulo, 05508-090, Brazil
Juliana G. Roscito & Miguel Trefaut Rodrigues
Center for Regenerative Therapies TU Dresden, Dresden, 01307, Germany
Andreas Petzold
Contributions
J.G.R. annotated the tegu genome, performed ATAC-seq, and analyzed the limb and eye loss trait. K.S. assembled and annotated the tegu genome and analyzed the limb and eye loss trait. G.P. performed the initial eye loss analysis. B.E.L. performed the TF-binding site analysis. A.P. helped with genome annotation. C.M., M.B. and J.G.R. performed luciferase assays. M.T.R. provided samples. M.H. conceived and supervised the study and performed data analysis. M.H., J.G.R. and K.S. wrote the manuscript. K.S. and J.G.R. made figures. All authors approved the final manuscript.
Competing interests
The authors declare no competing interests
Corresponding author
Correspondence to Michael Hiller.
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