Temporal ordering of substitutions in RNA evolution: Uncovering the structural evolution of the Human Accelerated Region 1

Costa, Maria Beatriz Walter; Siederdissen, Christian Höner zu; Tulpan, Dan; Stadler, Peter F.; Nowick, Katja

doi:10.1016/j.jtbi.2017.11.015

Cited by 7 publications

(6 citation statements)

References 19 publications

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“…In particular, zinc-finger genes, especially Krüppel -type zinc fingers (KZNFs), a family of transcription factors, were pinpointed as strong candidates to play a role in the speciation of other vertebrates [6]. In addition, various epigenetic mechanisms between species mediated by non-coding RNA (ncRNA) can also contribute to speciation [15–18].…”

Section: Introductionmentioning

confidence: 99%

Divergent evolution in the genomes of closely related lacertids,Lacerta viridisandL. bilineata, and implications for speciation

et al. 2018

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Background Lacerta viridis and Lacerta bilineata are sister species of European green lizards (eastern and western clades, respectively) that, until recently, were grouped together as the L. viridis complex. Genetic incompatibilities were observed between lacertid populations through crossing experiments, which led to the delineation of two separate species within the L. viridis complex. The population history of these sister species and processes driving divergence are unknown. We constructed the first high-quality de novo genome assemblies for both L. viridis and L. bilineata through Illumina and PacBio sequencing, with annotation support provided from transcriptome sequencing of several tissues. To estimate gene flow between the two species and identify factors involved in reproductive isolation, we studied their evolutionary history, identified genomic rearrangements, detected signatures of selection on non-coding RNA, and on protein-coding genes. Findings Here we show that gene flow was primarily unidirectional from L. bilineata to L. viridis after their split at least 1.15 million years ago. We detected positive selection of the non-coding repertoire; mutations in transcription factors; accumulation of divergence through inversions; selection on genes involved in neural development, reproduction, and behavior, as well as in ultraviolet-response, possibly driven by sexual selection, whose contribution to reproductive isolation between these lacertid species needs to be further evaluated. Conclusion The combination of short and long sequence reads resulted in one of the most complete lizard genome assemblies. The characterization of a diverse array of genomic features provided valuable insights into the demographic history of divergence among European green lizards, as well as key species differences, some of which are candidates that could have played a role in speciation. In addition, our study generated valuable genomic resources that can be used to address conservation-related issues in lacertids.

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Section: Introductionmentioning

confidence: 99%

Divergent evolution in the genomes of closely related lacertids,Lacerta viridisandL. bilineata, and implications for speciation

et al. 2018

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“…In a previous work on the HAR1 [19], we constructed a model showing that the most likely last step in turning the ancestral state into the modern human state was exactly the substitution at position 47 that distinguishes the modern human sequence from that of the Denisovan, which provides an independent support for the conclusions we drew from our visualizations.…”

Section: Resultsmentioning

confidence: 63%

Pairwise visual comparison of small RNA secondary structures with base pair probabilities

2019

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Background Predicted RNA secondary structures are typically visualized using dot-plots for base pair binding probabilities and planar graphs for unique structures, such as the minimum free energy structure. These are however difficult to analyze simultaneously. Results This work introduces a compact unified view of the most stable conformation of an RNA secondary structure and its base pair probabilities, which is called the C ircular S econdary S tructure B ase P airs P robabilities Plot ( CS 2 BP 2 -Plot ). Along with our design we provide access to a web server implementation of our solution that facilitates pairwise comparison of short RNA (and DNA) sequences up to 200 base pairs. The web server first calculates the minimum free energy secondary structure and the base pair probabilities for up to 10 RNA or DNA sequences using RNAfold and then provides a two panel comparative view that includes CS 2 BP 2 -Plots along with the traditional graph, planar and circular diagrams obtained with VARNA. The CS 2 BP 2 -Plots include highlighting of the nucleotide differences between two selected sequences using ClustalW local alignments. We also provide descriptive statistics, dot-bracket secondary structure representations and ClustalW local alignments for compared sequences. Conclusions Using circular diagrams and colour and weight-coded arcs, we demonstrate how a single image can replace the state-of-the-art dual representations (dot-plots and minimum free energy structures) for base-pair probabilities of RNA secondary structures while allowing efficient exploration and comparison of different RNA conformations via a web server front end. With that, we provide the community, especially the biologically oriented, with an intuitive tool for ncRNA visualization. Web-server: https://nrcmonsrv01.nrc.ca/cs2bp2plot

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“…’s structures and showed that human HAR1 RNA is more dynamic compared to that of chimpanzee [5]. In silico studies have been carried out to uncover the structural evolution of HAR1 RNA and have pointed to a more stable secondary structure in the human construct [6]. However, the exact structure and function of HAR1 remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, purification and crystallization of a putative critical bulge of HAR1 RNA

Lares

2019

PLoS ONE

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Non-coding RNAs have raised a lot of interest because of their capabilities to perform enzymatic reactions and regulate gene expression in various ways. Human Accelerated Region 1 (HAR1) has been identified during the search for highly conserved regions in mammalian genomes, over one hundred base pairs long, and with high rates of substitution in the human genome. Its potential for coding for a protein is very minimal. However, the HAR1 transcript has been computationally predicted to have a stable secondary structure. Previous structure-probing experiments have suggested that the majority of differences between human and chimp constructs are in helices, designated C and D. For this reason, a 47nt construct consisting of the C and D helices along with two additional C-G pairs was synthesized, purified, and crystallized, and its x-ray structure is reported in this study. The final structure is an artificial dimer, with a bulge that forms different conformations on each monomer. This bulge has been observed in predicted secondary structures, footprinting assays, enzymatic degradation assays, NMR studies, in silico studies, and in this crystalized dimer structure. It is proposed that the HAR1 transcript is a non-coding RNA that interacts with an unknown binding partner responsible for brain development through this inherent structural motif of bulged adenosines.

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Temporal ordering of substitutions in RNA evolution: Uncovering the structural evolution of the Human Accelerated Region 1

Cited by 7 publications

References 19 publications

Divergent evolution in the genomes of closely related lacertids,Lacerta viridisandL. bilineata, and implications for speciation

Divergent evolution in the genomes of closely related lacertids,Lacerta viridisandL. bilineata, and implications for speciation

Pairwise visual comparison of small RNA secondary structures with base pair probabilities

Synthesis, purification and crystallization of a putative critical bulge of HAR1 RNA

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