Structural insights into the molecular mechanism of the m6A writer complex

Methylation of adenosines at the N6 position (m6A) is a dynamic and abundant epitranscriptomic mark that regulates critical aspects of eukaryotic RNA metabolism in numerous biological processes. The RNA methyltransferases METTL3 and METTL14 are components of a multisubunit m6A writer complex whose enzymatic activity is substantially higher than the activities of METTL3 or METTL14 alone. The molecular mechanism underpinning this synergistic effect is poorly understood. Here we report the crystal structure of the catalytic core of the human m6A writer complex comprising METTL3 and METTL14. The structure reveals the heterodimeric architecture of the complex and donor substrate binding by METTL3. Structure-guided mutagenesis indicates that METTL3 is the catalytic subunit of the complex, whereas METTL14 has a degenerate active site and plays non-catalytic roles in maintaining complex integrity and substrate RNA binding. These studies illuminate the molecular mechanism and evolutionary history of eukaryotic m6A modification in post-transcriptional genome regulation.

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Adaptive convergent evolution of genome proofreading in SARS-CoV2: insights into the Eigen’s paradox

10.1101/2021.09.11.459886 ◽

2021 ◽

Author(s):

Keerthic Aswin ◽

Srinivasan Ramachandran ◽

Vivek T Natarajan

Keyword(s):

Convergent Evolution ◽

Genome Stability ◽

Evolutionary History ◽

Rna Binding ◽

Phylogenetic Analyses ◽

Comparative Genome Analysis ◽

The Family ◽

History Of ◽

Key Residues

AbstractEvolutionary history of coronaviruses holds the key to understand mutational behavior and prepare for possible future outbreaks. By performing comparative genome analysis of nidovirales that contain the family of coronaviruses, we traced the origin of proofreading, surprisingly to the eukaryotic antiviral component ZNFX1. This common recent ancestor contributes two zinc finger (ZnF) motifs that are unique to viral exonuclease, segregating them from DNA proof-readers. Phylogenetic analyses indicate that following acquisition, genomes of coronaviruses retained and further fine-tuned proofreading exonuclease, whereas related families harbor substitution of key residues in ZnF1 motif concomitant to a reduction in their genome sizes. Structural modelling followed by simulation suggests the role of ZnF in RNA binding. Key ZnF residues strongly coevolve with replicase, and the helicase involved in duplex RNA unwinding. Hence, fidelity of replication in coronaviruses is a result of convergent evolution, that enables maintenance of genome stability akin to cellular proofreading systems.

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Myxosporea (Myxozoa, Cnidaria) Lack DNA Cytosine Methylation

Molecular Biology and Evolution ◽

10.1093/molbev/msaa214 ◽

2020 ◽

Author(s):

Ryan Kyger ◽

Agusto Luzuriaga-Neira ◽

Thomas Layman ◽

Tatiana Orli Milkewitz Sandberg ◽

Devika Singh ◽

...

Keyword(s):

Evolutionary History ◽

Cytosine Methylation ◽

Bisulfite Sequencing ◽

Regulatory Mechanism ◽

Regulation Of Gene Expression ◽

Biological Processes ◽

Free Living ◽

Genome Bisulfite Sequencing ◽

History Of ◽

Dna Cytosine Methylation

Abstract DNA cytosine methylation is central to many biological processes, including regulation of gene expression, cellular differentiation, and development. This DNA modification is conserved across animals, having been found in representatives of sponges, ctenophores, cnidarians, and bilaterians, and with very few known instances of secondary loss in animals. Myxozoans are a group of microscopic, obligate endoparasitic cnidarians that have lost many genes over the course of their evolution from free-living ancestors. Here, we investigated the evolution of the key enzymes involved in DNA cytosine methylation in 29 cnidarians and found that these enzymes were lost in an ancestor of Myxosporea (the most speciose class of Myxozoa). Additionally, using whole-genome bisulfite sequencing, we confirmed that the genomes of two distant species of myxosporeans, Ceratonova shasta and Henneguya salminicola, completely lack DNA cytosine methylation. Our results add a notable and novel taxonomic group, the Myxosporea, to the very short list of animal taxa lacking DNA cytosine methylation, further illuminating the complex evolutionary history of this epigenetic regulatory mechanism.

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Deep ancestral introgression shapes evolutionary history of dragonflies and damselflies

10.1101/2020.06.25.172619 ◽

2020 ◽

Author(s):

Anton Suvorov ◽

Celine Scornavacca ◽

M. Stanley Fujimoto ◽

Paul Bodily ◽

Mark Clement ◽

...

Keyword(s):

Evolutionary History ◽

Biological Processes ◽

Species Relationships ◽

Phenotypic Characteristics ◽

Tree Model ◽

Environmental Pressures ◽

Evolutionary Force ◽

Extant Species ◽

History Of ◽

Strictly Binary Tree

SUMMARYIntrogression is arguably one of the most important biological processes in the evolution of groups of related species, affecting at least 10% of the extant species in the animal kingdom. Introgression reduces genetic divergence between species, and in some cases can be highly beneficial, facilitating rapid adaptation to ever-changing environmental pressures. Introgression also significantly impacts inference of phylogenetic species relationships where a strictly binary tree model cannot adequately explain reticulate net-like species relationships. Here we use phylogenomic approaches to understand patterns of introgression along the evolutionary history of a unique, non-model, relic insect system: dragonflies and damselflies (Odonata). We demonstrate that introgression is a pervasive evolutionary force across various taxonomic levels within Odonata. In particular, we show that the morphologically “intermediate” species of Anisozygoptera (one of the three primary suborders within Odonata besides Zygoptera and Anisoptera), which retain phenotypic characteristics of the other two suborders, experienced high levels of introgression probably coming from zygopteran genomes. Additionally, we found evidence for multiple cases of deep inter-familial ancestral introgression. However, weaker evidence of introgression was found within more recently diverged focal clades: Aeshnidae, Gomphidae+Petaluridae and Libellulidae.

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High Resolution Structural Insights into Heliorhodopsin Family

10.1101/767665 ◽

2019 ◽

Author(s):

K. Kovalev ◽

D. Volkov ◽

R. Astashkin ◽

A. Alekseev ◽

I. Gushchin ◽

...

Keyword(s):

Active Site ◽

Bioinformatic Analysis ◽

Proton Acceptor ◽

Water Molecules ◽

Primary Proton ◽

Biological Processes ◽

New Family ◽

Charged Amino Acids ◽

And Function ◽

Structural Insights

AbstractRhodopsins are the most abundant light-harvesting proteins. A new family of rhodopsins, heliorhodopsins (HeRs), was recently discovered. In opposite to the known rhodopsins their N-termini face the cytoplasm. HeRs structure and function remain unknown. We present structures of two HeR-48C12 states at 1.5 Å showing its remarkable difference from all known rhodopsins. Its internal extracellular part is completely hydrophobic, while the cytoplasmic part comprises a cavity (’active site’), surrounded by charged amino acids and containing a cluster of water molecules, presumably being a primary proton acceptor from the Schiff base. At acidic pH a planar triangle molecule (acetate) is present in the ‘active site’ which demonstrated its ability to maintain such anions as carbonate or nitrate. Structure-based bioinformatic analysis identified 10 subfamilies of HeRs suggesting their diverse biological functions. The structures and available data suggest an enzymatic activity of HeR-48C12 subfamily and their possible involvement into fundamental redox biological processes.

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Evolutionary history of double-stranded RNA binding proteins in plants: identification of new cofactors involved in easiRNA biogenesis

Plant Molecular Biology ◽

10.1007/s11103-016-0448-9 ◽

2016 ◽

Vol 91 (1-2) ◽

pp. 131-147 ◽

Cited By ~ 8

Author(s):

Marion Clavel ◽

Thierry Pélissier ◽

Thomas Montavon ◽

Marie-Aude Tschopp ◽

Marie-Noëlle Pouch-Pélissier ◽

...

Keyword(s):

Evolutionary History ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Double Stranded Rna ◽

History Of

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Evidence for an ancient bilaterian origin of the RAG-like transposon

10.21203/rs.2.19531/v1 ◽

2019 ◽

Author(s):

Eliza C. Martin ◽

Celia Vicari ◽

Louis Tsakou-Ngouafo ◽

Pierre Pontarotti ◽

Andrei J. Petrescu ◽

...

Keyword(s):

Amino Acids ◽

Adaptive Immunity ◽

Active Site ◽

Evolutionary History ◽

Phylogenetic Analyses ◽

Target Site ◽

Inverted Repeats ◽

Adjacent Gene ◽

Terminal Inverted Repeats ◽

History Of

Abstract Background V(D)J recombination is essential for adaptive immunity in jawed vertebrates and is initiated by the RAG1-RAG2 endonuclease. The RAG1 and RAG2 genes are thought to have evolved from a RAGL (RAG-like) transposon containing convergently-oriented RAG1-like (RAG1L) and RAG2-like (RAG2L) genes. Elements resembling this presumptive evolutionary precursor have thus far only been detected convincingly in deuterostomes, leading to the model that the RAGL transposon first appeared in an early deuterostome. Results We have identified numerous RAGL transposons in the genomes of protostomes, including oysters and mussels (phylum Mollusca) and a ribbon worm (phylum Nemertea), and in the genomes of several cnidarians. Phylogenetic analyses indicate that the RAGL transposon family evolved in a vertical manner within the Bilateria clade. Many of the RAGL transposons identified in protostomes are intact elements containing convergently oriented RAG1L and RAG2L genes flanked by terminal inverted repeats (TIRs) and target site duplications with striking similarities with the corresponding elements in deuterostomes. In addition, protostome genomes contain numerous intact RAG1L-RAG2L adjacent gene pairs that lack detectable flanking TIRs. Domains and critical active site and structural amino acids needed for endonuclease and transposase activity are present and conserved in many of the predicted RAG1L and RAG2L proteins encoded in protostome genomes. Conclusions Active RAGL transposons were present in multiple protostome lineages and were transmitted vertically during protostome evolution. It appears that the RAGL transposon family was broadly active during bilaterian evolution, undergoing multiple duplication and loss/fossilization events, with the RAGL genes that persist in present day protostomes perhaps constituting both active RAGL transposons and domesticated RAGL genes. Our findings indicate that the RAGL transposon arose earlier in evolution than previously thought, either in an early bilaterian or prior to the divergence of bilaterians and non-bilaterians, and alter our understanding of the evolutionary history of this important transposon family.

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Structural insights into the molecular mechanism underlying Sirt5-catalyzed desuccinylation of histone peptides

Biochemical Journal ◽

10.1042/bcj20180745 ◽

2019 ◽

Vol 476 (2) ◽

pp. 211-223 ◽

Cited By ~ 1

Author(s):

Tianrong Hang ◽

Wanbiao Chen ◽

Minhao Wu ◽

Li Zhan ◽

Chengliang Wang ◽

...

Keyword(s):

Molecular Mechanism ◽

Main Chain ◽

Regulatory Mechanism ◽

Biological Processes ◽

Biological Functions ◽

Damage Repair ◽

Biochemical Assays ◽

Functional Consequences ◽

Enzyme Recognition ◽

Structural Insights

Abstract Histone modification is a ubiquitous regulatory mechanism involved in a variety of biological processes, including gene expression, DNA damage repair, cell differentiation, and ontogenesis. Succinylation sites on histones have been identified and may have functional consequences. Here, we demonstrate that human sirtuin 5 (Sirt5) catalyzes the sequence-selective desuccinylation of numerous histone succinyl sites. Structural studies of Sirt5 in complex with four succinyl peptides indicate an essential role for the conserved main chain hydrogen bonds formed by the succinyl lysine (0), +1, and +3 sites for substrate-enzyme recognition. Furthermore, biochemical assays reveal that the proline residue at the +1 site of the histone succinylation substrate is unfavorable for Sirt5 interaction. Our findings illustrate the molecular mechanism underlying the sequence-selective desuccinylase activity of Sirt5 and provide insights for further studies of the biological functions associated with histone succinylation and Sirt5.

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Identification of RAG-like transposons in protostomes suggests an ancient bilaterian origin of the RAG-like transposon family

10.21203/rs.2.19531/v2 ◽

2020 ◽

Author(s):

Eliza C. Martin ◽

Celia Vicari ◽

Louis Tsakou-Ngouafo ◽

Pierre Pontarotti ◽

Andrei J. Petrescu ◽

...

Keyword(s):

Amino Acids ◽

Adaptive Immunity ◽

Active Site ◽

Evolutionary History ◽

Phylogenetic Analyses ◽

Inverted Repeats ◽

Adjacent Gene ◽

Terminal Inverted Repeats ◽

History Of ◽

Vertical Evolution

Abstract Background V(D)J recombination is essential for adaptive immunity in jawed vertebrates and is initiated by the RAG1-RAG2 endonuclease. The RAG1 and RAG2 genes are thought to have evolved from a RAGL (RAG-like) transposon containing convergently-oriented RAG1-like (RAG1L) and RAG2-like (RAG2L) genes. Elements resembling this presumptive evolutionary precursor have thus far only been detected convincingly in deuterostomes, leading to the model that the RAGL transposon first appeared in an early deuterostome. Results We have identified numerous RAGL transposons in the genomes of protostomes, including oysters and mussels (phylum Mollusca) and a ribbon worm (phylum Nemertea), and in the genomes of several cnidarians. Phylogenetic analyses are consistent with vertical evolution of the RAGL transposon family within the Bilateria clade and with its presence in the bilaterian ancestor. Many of the RAGL transposons identified in protostomes are intact elements containing convergently oriented RAG1L and RAG2L genes flanked by terminal inverted repeats (TIRs) and target site duplications with striking similarities with the corresponding elements in deuterostomes. In addition, protostome genomes contain numerous intact RAG1L-RAG2L adjacent gene pairs that lack detectable flanking TIRs. Domains and critical active site and structural amino acids needed for endonuclease and transposase activity are present and conserved in many of the predicted RAG1L and RAG2L proteins encoded in protostome genomes. Conclusions Active RAGL transposons were present in multiple protostome lineages and were likely transmitted vertically during protostome evolution. It appears that the RAGL transposon family was broadly active during bilaterian evolution, undergoing multiple duplication and loss/fossilization events, with the RAGL genes that persist in present day protostomes perhaps constituting both active RAGL transposons and domesticated RAGL genes. Our findings raise the possibility that the RAGL transposon arose earlier in evolution than previously thought, either in an early bilaterian or prior to the divergence of bilaterians and non-bilaterians, and alter our understanding of the evolutionary history of this important transposon family.

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Elaborating the role of reflection and individual differences in the study of folk-economic beliefs

Behavioral and Brain Sciences ◽

10.1017/s0140525x18000274 ◽

2018 ◽

Vol 41 ◽

Author(s):

Kevin Arceneaux

Keyword(s):

Decision Making ◽

Individual Differences ◽

Cognitive Processes ◽

Evolutionary History ◽

Behavioral Responses ◽

History Of ◽

Economic Beliefs

AbstractIntuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.

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A Dynamic Systems Approach to Personality

European Psychologist ◽

10.1027//1016-9040.6.3.172 ◽

2001 ◽

Vol 6 (3) ◽

pp. 172-176 ◽

Cited By ~ 14

Author(s):

Lawrence A. Pervin

Keyword(s):

Dynamic Systems ◽

Systems Approach ◽

Biological Processes ◽

Recent Advances ◽

Dynamic View ◽

The Future ◽

History Of

David Magnusson has been the most articulate spokesperson for a holistic, systems approach to personality. This paper considers three concepts relevant to a dynamic systems approach to personality: dynamics, systems, and levels. Some of the history of a dynamic view is traced, leading to an emphasis on the need for stressing the interplay among goals. Concepts such as multidetermination, equipotentiality, and equifinality are shown to be important aspects of a systems approach. Finally, attention is drawn to the question of levels of description, analysis, and explanation in a theory of personality. The importance of the issue is emphasized in relation to recent advances in our understanding of biological processes. Integrating such advances into a theory of personality while avoiding the danger of reductionism is a challenge for the future.

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