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Table of Contents

April 2021

Mitochondrial DNA (mtDNA) and plastid DNA (ptDNA) encode vital bioenergetic apparatus, and mutations in these organelle DNA (oDNA) molecules can be devastating. In the germline of several animals, a genetic "bottleneck" increases cell-to-cell variance in mtDNA heteroplasmy, allowing purifying selection to act to maintain low proportions of mutant mtDNA. However, most eukaryotes do not sequester a germline early in development, and even the animal bottleneck remains poorly understood. How then do eukaryotic organelles avoid Muller’s ratchet—the gradual buildup of deleterious oDNA mutations? Edwards et al. construct a comprehensive and predictive genetic model, quantitatively describing how different mechanisms segregate and decrease oDNA damage across eukaryotes. They apply this theory to characterize the animal bottleneck with recent single-cell observations in diverse mouse models. Further, they show that gene conversion is a particularly powerful mechanism to increase beneficial cell-to-cell variance without depleting oDNA copy number, explaining the benefit of observed oDNA recombination in diverse organisms which do not sequester animal-like germlines (for example, sponges, corals, fungi, and plants). The image depicts the wide range of organisms considered, including those with and without fixed body plans.

Image Credit: Gemma Lofthouse

Essays

How accurately can we assess zoonotic risk?

Michelle Wille, Jemma L. Geoghegan, Edward C. Holmes

Human protection drives the emergence of a new coping style in animals

Bastien Sadoul, Daniel T. Blumstein, Sébastien Alfonso, Benjamin Geffroy

Research Articles

Avoiding organelle mutational meltdown across eukaryotes with or without a germline bottleneck

David M. Edwards, Ellen C. Røyrvik, Joanna M. Chustecki, Konstantinos Giannakis, Robert C. Glastad, Arunas L. Radzvilavicius, Iain G. Johnston

Signatures of optimal codon usage in metabolic genes inform budding yeast ecology

Abigail Leavitt LaBella, Dana A. Opulente, Jacob L. Steenwyk, Chris Todd Hittinger, Antonis Rokas

The dinucleotide composition of the Zika virus genome is shaped by conflicting evolutionary pressures in mammalian hosts and mosquito vectors

Jelke J. Fros, Imke Visser, Bing Tang, Kexin Yan, Eri Nakayama, Tessa M. Visser, Constantianus J. M. Koenraadt, Monique M. van Oers, Gorben P. Pijlman, Andreas Suhrbier, Peter Simmonds

Peroxiredoxin alleviates the fitness costs of imidacloprid resistance in an insect pest of rice

Rui Pang, Ke Xing, Longyu Yuan, Zhikun Liang, Meng Chen, Xiangzhao Yue, Yi Dong, Yan Ling, Xionglei He, Xianchun Li, Wenqing Zhang

Evaluation of COVID-19 vaccination strategies with a delayed second dose

Seyed M. Moghadas, Thomas N. Vilches, Kevin Zhang, Shokoofeh Nourbakhsh, Pratha Sah, Meagan C. Fitzpatrick, Alison P. Galvani

Validation testing to determine the sensitivity of lateral flow testing for asymptomatic SARS-CoV-2 detection in low prevalence settings: Testing frequency and public health messaging is key

Jack Ferguson, Steven Dunn, Angus Best, Jeremy Mirza, Benita Percival, Megan Mayhew, Oliver Megram, Fiona Ashford, Thomas White, Emma Moles-Garcia, Liam Crawford, Tim Plant, Andrew Bosworth, Michael Kidd, Alex Richter, Jonathan Deeks, Alan McNally

Anesthetics fragment hippocampal network activity, alter spine dynamics, and affect memory consolidation

Wei Yang, Mattia Chini, Jastyn A. Pöpplau, Andrey Formozov, Alexander Dieter, Patrick Piechocinski, Cynthia Rais, Fabio Morellini, Olaf Sporns, Ileana L. Hanganu-Opatz, J. Simon Wiegert

Smoothened transduces Hedgehog signals via activity-dependent sequestration of PKA catalytic subunits

Corvin D. Arveseth, John T. Happ, Danielle S. Hedeen, Ju-Fen Zhu, Jacob L. Capener, Dana Klatt Shaw, Ishan Deshpande, Jiahao Liang, Jiewei Xu, Sara L. Stubben, Isaac B. Nelson, Madison F. Walker, Kouki Kawakami, Asuka Inoue, Nevan J. Krogan, David J. Grunwald, Ruth Hüttenhain, Aashish Manglik, Benjamin R. Myers

DAF-16/FoxO and DAF-12/VDR control cellular plasticity both cell-autonomously and via interorgan signaling

Ulkar Aghayeva, Abhishek Bhattacharya, Surojit Sural, Eliza Jaeger, Matthew Churgin, Christopher Fang-Yen, Oliver Hobert

PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype

Giorgia Fanelli, Marco Romano, Estefania Nova-Lamperti, Mariana Werner Sunderland, Alessandra Nerviani, Cristiano Scottà, Michele Bombardieri, Sergio A. Quezada, Steven H. Sacks, Randolph J. Noelle, Costantino Pitzalis, Robert I. Lechler, Giovanna Lombardi, Pablo D. Becker

Related Articles

Neural stem cells traffic functional mitochondria via extracellular vesicles

Luca Peruzzotti-Jametti, Joshua D. Bernstock, Cory M. Willis, Giulia Manferrari, Rebecca Rogall, Erika Fernandez-Vizarra, James C. Williamson, Alice Braga, Aletta van den Bosch, Tommaso Leonardi, Grzegorz Krzak, Ágnes Kittel, Cristiane Benincá, Nunzio Vicario, Sisareuth Tan, Carlos Bastos, Iacopo Bicci, Nunzio Iraci, Jayden A. Smith, Ben Peacock, Karin H. Muller, Paul J. Lehner, Edit Iren Buzas, Nuno Faria, Massimo Zeviani, Christian Frezza, Alain Brisson, Nicholas J. Matheson, Carlo Viscomi, Stefano Pluchino

Farnesyl pyrophosphate is a new danger signal inducing acute cell death

Jing Chen, Xiaochen Zhang, Liping Li, Xianqiang Ma, Chunxiao Yang, Zhaodi Liu, Chenyang Li, Maria J. Fernandez-Cabezudo, Basel K. al-Ramadi, Chuan Wu, Weishan Huang, Yong Zhang, Yonghui Zhang, Wanli Liu

Related Articles

HMGCR inhibition stabilizes the glycolytic enzyme PKM2 to support the growth of renal cell carcinoma

Jiajun Huang, Xiaoyu Zhao, Xiang Li, Jiwei Peng, Weihao Yang, Shengli Mi

Molecular basis of F-actin regulation and sarcomere assembly via myotilin

Julius Kostan, Miha Pavšič, Vid Puž, Thomas C. Schwarz, Friedel Drepper, Sibylle Molt, Melissa Ann Graewert, Claudia Schreiner, Sara Sajko, Peter F. M. van der Ven, Adekunle Onipe, Dmitri I. Svergun, Bettina Warscheid, Robert Konrat, Dieter O. Fürst, Brigita Lenarčič, Kristina Djinović-Carugo

Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies

Xing Zhu, Dhiraj Mannar, Shanti S. Srivastava, Alison M. Berezuk, Jean-Philippe Demers, James W. Saville, Karoline Leopold, Wei Li, Dimiter S. Dimitrov, Katharine S. Tuttle, Steven Zhou, Sagar Chittori, Sriram Subramaniam

The structure of MgtE in the absence of magnesium provides new insights into channel gating

Fei Jin, Minxuan Sun, Takashi Fujii, Yurika Yamada, Jin Wang, Andrés D. Maturana, Miki Wada, Shichen Su, Jinbiao Ma, Hironori Takeda, Tsukasa Kusakizako, Atsuhiro Tomita, Yoshiko Nakada-Nakura, Kehong Liu, Tomoko Uemura, Yayoi Nomura, Norimichi Nomura, Koichi Ito, Osamu Nureki, Keiichi Namba, So Iwata, Ye Yu, Motoyuki Hattori

Short Reports

Bacterial persisters are a stochastically formed subpopulation of low-energy cells

Sylvie Manuse, Yue Shan, Silvia J. Canas-Duarte, Somenath Bakshi, Wei-Sheng Sun, Hirotada Mori, Johan Paulsson, Kim Lewis

Neurocognitive processing efficiency for discriminating human non-alarm rather than alarm scream calls

Sascha Frühholz, Joris Dietziker, Matthias Staib, Wiebke Trost

Phe-Gly motifs drive fibrillization of TDP-43’s prion-like domain condensates

David Pantoja-Uceda, Cristiana Stuani, Douglas V. Laurents, Ann E. McDermott, Emanuele Buratti, Miguel Mompeán

Methods and Resources

Quantitative proteome comparison of human hearts with those of model organisms

Nora Linscheid, Alberto Santos, Pi Camilla Poulsen, Robert W. Mills, Kirstine Calloe, Ulrike Leurs, Johan Z. Ye, Christian Stolte, Morten B. Thomsen, Bo H. Bentzen, Pia R. Lundegaard, Morten S. Olesen, Lars J. Jensen, Jesper V. Olsen, Alicia Lundby

Meta-Research Articles

The methodological quality of 176,620 randomized controlled trials published between 1966 and 2018 reveals a positive trend but also an urgent need for improvement

Christiaan H. Vinkers, Herm J. Lamberink, Joeri K. Tijdink, Pauline Heus, Lex Bouter, Paul Glasziou, David Moher, Johanna A. Damen, Lotty Hooft, Willem M. Otte

The evolving role of preprints in the dissemination of COVID-19 research and their impact on the science communication landscape

Nicholas Fraser, Liam Brierley, Gautam Dey, Jessica K. Polka, Máté Pálfy, Federico Nanni, Jonathon Alexis Coates

Discovery Reports

A functional bacteria-derived restriction modification system in the mitochondrion of a heterotrophic protist

David S. Milner, Jeremy G. Wideman, Courtney W. Stairs, Cory D. Dunn, Thomas A. Richards

The dominantly expressed class II molecule from a resistant MHC haplotype presents only a few Marek’s disease virus peptides by using an unprecedented binding motif

Samer Halabi, Michael Ghosh, Stefan Stevanović, Hans-Georg Rammensee, Luca D. Bertzbach, Benedikt B. Kaufer, Martin C. Moncrieffe, Bernd Kaspers, Sonja Härtle, Jim Kaufman