Evolutionary models predict potential mechanisms of escape from mutational meltdown

Mutagenic drugs are promising candidates for the treatment of various RNA virus infections. Increasing the mutation rate of the virus leads to rapid accumulation of deleterious mutation load, which is proposed to ultimately result in extinction as described by the theoretical concepts of mutational meltdown and lethal mutagenesis. However, the conditions and potential mechanisms of viral escape from the effects of mutagenic drugs have not been conceptually explored. Here we apply a computational approach to quantify the population dynamics and genetics of a population under high mutation rates and discuss the likelihood of adaptation to a mutagenic drug by means of three proposed mechanisms: (1) a proportion of “traditional” beneficial mutations that increase growth/fitness, (2) a mutation rate modifier (i.e., evolution of resistance to the mutagenic drug) that reduces the mutation rate, and (3) a modifier of the distribution of fitness effects, which either decreases or increases deleterious effects of mutations (i.e., evolution of tolerance to the mutagenic drug). We track the population dynamics and genetics of evolving populations and find that successful adaptations have to appear early to override the increasing mutational load and rescue the population from its imminent extinction. We highlight that the observed stochasticity of adaptation, especially by means of modifiers of the distribution of fitness effects, is difficult to capture in experimental trials, which may leave potential dangers of the use of mutagenic treatments unexposed

The impact of frequently neglected model violations on bacterial recombination rate estimation: a case study in <i>Mycobacterium canettii</i> and <i>Mycobacterium tuberculosis</i>

Abstract Mycobacterium canettiiMycobacterium tuberculosisM. tuberculosisM. canettiiM. canettiiM. tuberculosi

Ethics of DNA research on human remains: Five globally applicable guidelines

We are a group of archaeologists, anthropologists, curators and geneticists representing diverse global communities and 31 countries. All of us met in a virtual workshop dedicated to ethics in ancient DNA research held in November 2020. There was widespread agreement that globally applicable ethical guidelines are needed, but that recent recommendations grounded in discussion about research on human remains from North America are not always generalizable worldwide. Here we propose the following globally applicable guidelines, taking into consideration diverse contexts. These hold that: (1) researchers must ensure that all regulations were followed in the places where they work and from which the human remains derived; (2) researchers must prepare a detailed plan prior to beginning any study; (3) researchers must minimize damage to human remains; (4) researchers must ensure that data are made available following publication to allow critical re-examination of scientific findings; and (5) researchers must engage with other stakeholders from the beginning of a study and ensure respect and sensitivity to stakeholder perspectives. We commit to adhering to these guidelines and expect they will promote a high ethical standard in DNA research on human remains going forward.Fil: Alpaslan Roodenberg, Songül. Harvard Medical School; Estados Unidos. Universidad de Viena; AustriaFil: Anthony, David. Harvard University; Estados UnidosFil: Babiker, Hiba. Max Planck Institute For The Science Of Human History; Estados UnidosFil: Bánffy, Eszter. No especifíca;Fil: Booth, Thomas. No especifíca;Fil: Capone, Patricia. Harvard University; Estados UnidosFil: Deshpande Mukherjee, Arati. No especifíca;Fil: Eisenmann, Stefanie. Institut Max Planck for Evolutionary Anthropology; AlemaniaFil: Fehren Schmitz, Lars. University of California; Estados UnidosFil: Frachetti, Michael. Washington University in St. Louis; Estados UnidosFil: Fujita, Ricardo. Universidad de San Martín de Porres; PerúFil: Frieman, Catherine J.. The Australian National University; AustraliaFil: Fu, Qiaomei. No especifíca;Fil: Gibbon, Victoria. University of Cape Town; SudáfricaFil: Haak, Wolfgang. Max Planck Institute For The Science Of Human History; AlemaniaFil: Hajdinjak, Mateja. The Francis Crick Institute; Reino UnidoFil: Hofmann, Kerstin P.. Deutsches Archäologisches Institut; AlemaniaFil: Holguin, Brian. University of California; Estados UnidosFil: Inomata, Takeshi. University of Arizona; Estados UnidosFil: Kanzawa Kiriyama, Hideaki. National Museum Of Nature And Science; JapónFil: Keegan, William. University Of Florida. Florida Museum Of History; Estados UnidosFil: Kelso, Janet. Institut Max Planck for Evolutionary Anthropology; AlemaniaFil: Krause, Johannes. Institut Max Planck for Evolutionary Anthropology; AlemaniaFil: Kumaresan, Ganesan. Madurai Kamaraj University; IndiaFil: Kusimba, Chapurukha. University of Florida; Estados UnidosFil: Kusimba, Sibel. University of Florida; Estados UnidosFil: Lalueza Fox, Carles. Consejo Superior de Investigaciones Científicas; EspañaFil: Llamas, Bastien. University of Adelaide; AustraliaFil: MacEachern, Scott. University of Duke; Estados UnidosFil: Mallick, Swapan. Harvard Medical School; Estados UnidosFil: Matsumura, Hirofumi. Sapporo Medical University; JapónFil: Morales Arce, Ana Y.. University of Bern; SuizaFil: Motuzaite Matuzeviciute, Giedre. Vilniaus Universitetas; LituaniaFil: Mushrif Tripathy, Veena. Deccan College Post Graduate and Research Institute; IndiaFil: Nakatsuka, Nathan. Harvard Medical School; Estados UnidosFil: Nores, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Antropología de Córdoba. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Instituto de Antropología de Córdoba; ArgentinaFil: Ogola, Christine. National Museums Of Kenya; KeniaFil: Okumura, Mercedes. Universidade de Sao Paulo; BrasilFil: Patterson, Nick. Harvard University; Estados UnidosFil: Pinhasi, Ron. Universidad de Viena; AustriaFil: Prasad, Samayamantri P. R.. No especifíca;Fil: Prendergast, Mary E.. Rice University; Estados UnidosFil: Punzo, Jose Luis. No especifíca;Fil: Reich, David. Harvard University; Estados Unidos. Harvard Medical School; Estados UnidosFil: Sawafuji, Rikai. The Graduate University For Advanced Studies; JapónFil: Sawchuk, Elizabeth. University of Alberta; CanadáFil: Schiffels, Stephan. Institut Max Planck for Evolutionary Anthropology; AlemaniaFil: Sedig, Jakob. Harvard University; Estados Unidos. Harvard Medical School; Estados UnidosFil: Shnaider, Svetlana. Centre National de la Recherche Scientifique; FranciaFil: Sirak, Kendra. Harvard University; Estados Unidos. Harvard Medical School; Estados UnidosFil: Skoglund, Pontus. The Francis Crick Institute; Reino UnidoFil: Slon, Viviane. Universitat Tel Aviv; IsraelFil: Snow, Meradeth. University Of Montana Missoula; Estados UnidosFil: Soressi, Marie. Leiden University; Países BajosFil: Spriggs, Matthew. The Australian National University; AustraliaFil: Stockhammer, Philipp W.. Ludwig Maximilians Universitat; Alemania. Institut Max Planck for Evolutionary Anthropology; AlemaniaFil: Szécsényi Nagy, Anna. No especifíca;Fil: Thangaraj, Kumarasamy. Centre for Cellular and Molecular Biology; IndiaFil: Tiesler, Vera. Universidad Autónoma de Yucatán; MéxicoFil: Tobler, Ray. University of Adelaide; AustraliaFil: Wang, Chuan Chao. Xiamen University; ChinaFil: Warinner, Christina. Institut Max Planck for Evolutionary Anthropology; Alemania. Harvard University; Estados UnidosFil: Yasawardene, Surangi. No especifíca;Fil: Zahir, Muhammad. Hazara University; Pakistá

Ethics of DNA research on human remains: five globally applicable guidelines.

We are a group of archaeologists, anthropologists, curators and geneticists representing diverse global communities and 31 countries. All of us met in a virtual workshop dedicated to ethics in ancient DNA research held in November 2020. There was widespread agreement that globally applicable ethical guidelines are needed, but that recent recommendations grounded in discussion about research on human remains from North America are not always generalizable worldwide. Here we propose the following globally applicable guidelines, taking into consideration diverse contexts. These hold that: (1) researchers must ensure that all regulations were followed in the places where they work and from which the human remains derived; (2) researchers must prepare a detailed plan prior to beginning any study; (3) researchers must minimize damage to human remains; (4) researchers must ensure that data are made available following publication to allow critical re-examination of scientific findings; and (5) researchers must engage with other stakeholders from the beginning of a study and ensure respect and sensitivity to stakeholder perspectives. We commit to adhering to these guidelines and expect they will promote a high ethical standard in DNA research on human remains going forward