John W. Drake's research while affiliated with National Institute of Environmental Health Sciences and other places

... There are two factors worth noting that theoretically establish a minimal limit to mutation rate. First, physiological limitations of DNA repair and replication probably prevent reduction of the genomic mutation rate to zero (Drake 1990(Drake , 1993Kondrashov 1995); it could be energetically costly or physicochemically impossible to prevent all replication errors. A second factor that might prevent complete reduction of the mutation rate is the necessity of variation; ...

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The Evolution of a High Mutation Rate and Declining Fitness in Asexual Populations

... As Jan Drake polymerases. A simplified sketch of this polymeraseproofreading model is presented in Figure 2. has pointed out, it was fortunate that A·T→G ·C mutations were investigated early on for the tsL141 allele, The model treats polymerization and proofreading as two possible outcomes of a series of random events, otherwise it may not have been identified as an antimutator (Drake 1992). which take place after a dNTP (right or wrong) binds to the enzyme. ...

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DNA Polymerase Fidelity: From Genetics Toward a Biochemical Understanding

... The thermotolerant capacity of different microbial species induced by various horizontal gene transfer mechanisms has been reported such as conjugation [43], natural transformation [44], transduction [45], gene transfer through membrane vesicles, nanotubes and nano pods [46]. Analysis of genome mutation studies in Thermus thermophilus and Sulfolobus acidocaldarius showed a lower frequency of base substitution occurs in thermophilic when compare with the mesophilic organisms [47]. These results suggest that a stringent DNA repair mechanism is maintained in the thermophilic organisms for the stability of their genome. ...

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Proteomic perspectives on thermotolerant microbes: an updated review

... Finally, we found a correlation between survival (low decay rate m) and reproduction (high relative growth, Fig. 4B), as in previous studies with phages (correlations: De Paepe & Taddei, 2006;Dessau et al., 2012;confirmed trade-offs: Heineman & Brown, 2012;García-Villada & Drake, 2013). Interestingly, we did not find a correlation when reproduction was calculated as the multiplication rate following the classic example in De Paepe & Taddei (2006) (Fig. 4B). ...

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Life history diversity and signals of trade-offs in a large group of chloroviruses

... We compromised on a readily accessible title, followed by "De mutatis. . ." as a subtitle [17]. This was long my favorite title, joined later by my favorite running head, composed for a paper in the JBC that dissected a mutator DNA polymerase using fidelity assays based most on in vivo systems: In Vivo Veritas. ...

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Twists and turns

... Replication mode of some RNA viruses, such as vesicular stomatitis virus [12] and the poliovirus [88] is quite close to GR, with multiple rounds of RNA copying inside the cell. Other RNA viruses, such as bacteriophages Qβ [36] and φ6 [8], as well as the turnip mosaic virus [64], replicate in a way that is very reminiscent of SMR. At the same time, since many other viruses operate in a regime somewhere between those two extremes, hence, it is convenient to represent the mode of replication using a continuous parameter 0 < α ≤ 1 [85], with α 0 corresponding to SMR, and 0 < α ≤ 1 describing GR, with α = 1 being a situation, where both positive and negative strands replicate at the same rate. ...

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Mathematical model of replication-mutation dynamics in coronaviruses

... When rates of spontaneous mutation are expressed per genome replication, different broad groups of organisms display characteristic values [31,32]: of the order of 0.001 for DNA-based microbes (including both viral and cellular organisms); of the order of 0.01 for higher eukaryotes; from the order of 0.01 to the order of 0.1 for retroviruses and from the order of 0.1 to the order of 1 for RNA viruses exclusive of retroviruses [47,88,3,30]. This wide range of mutation rates of RNA viruses suggests that it is inappropriate to gather RNA viruses together into a single group that is subject to different evolutionary rules than organisms with DNA genomes. ...

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Stochastic Modeling and Simulation of Viral Evolution

... It has been observed that mutation rate estimates can differ between MA experiments and specific locus methods, even with carefully chosen reporter genes (Table 1), and these differences are often significant (paired Student's ttest, two-tailed P = 0.029) (Drake 2012). These discrepancies likely arise in part because mutation rates vary among individual nucleotide types (Long et al. , 2018Kucukyildirim et al. 2016), depending on their neighboring content (Sung et al. 2012), and vary among chromosomal regions (Long et al. 2014;Dillon et al. 2015;Sung et al. 2015;Niccum et al. 2019). ...

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Estimation of the Genome-Wide Mutation Rate and Spectrum in the Archaeal Species Haloferax volcanii

... The T4 phage strain used in this study is highly virulent and rapidly lyses the cell after infection (it is an obligate lytic, [2]). Phage T4r (T4 rapid) lacks the lysis inhibition (LIN) genes of wild-type T4 and rapidly lyses bacteria, even multiply infected "super-infected" bacteria, with resultant relatively low titer yields compared to wild-type T4 [3]. Because of the rapid lysis of T4r infected bacteria any survival of a low number N O of bacteria can only be due to either previously acquired resistance (Darwinian random mutations) or a kind of rapid response by the stress-challenged bacteria, which can be called Lamarckian in a certain sense of the word. ...

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Microfluidic Ecology Unravels the Genetic and Ecological Drivers of T4r Bacteriophage Resistance in E. coli: Insights into Biofilm-Mediated Evolution

... Despite the information learned from structural and biochemical studies of DNA polymerases, Jan concluded that fidelities of wild-type and mutant RB69 DNA polymerases determined in vitro only partially reflected their fidelities in vivo (Bebenek et al. 2002). For example, biochemical studies of engineered RB69 DNA polymerases showed that increasing the size of the nucleotide-binding pocket reduced nucleotide insertion fidelity, but that was countered by in vivo mutation studies (Trzemecka et al. 2010) that forced reconsideration of the biochemical studies (Xia et al. 2011). Hence, there is a real and continuing need for in vivo replication fidelity experiments. ...

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John W. (Jan) Drake: A Biochemical View of a Geneticist Par Excellence