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Jeffrey D. Jensen
School of Life Sciences, Arizona State University, Tempe, AZ 85287, United States

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Accepted manuscript
Published: 14 June 2021 in Genetics
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It has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations could generate selective sweep-like effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites - both in the presence and absence of interference amongst deleterious mutations - and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious fixations are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of FST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration.

ACS Style

Parul Johri; Brian Charlesworth; Emma K Howell; Michael Lynch; Jeffrey D Jensen. Revisiting the Notion of Deleterious Sweeps. Genetics 2021, 1 .

AMA Style

Parul Johri, Brian Charlesworth, Emma K Howell, Michael Lynch, Jeffrey D Jensen. Revisiting the Notion of Deleterious Sweeps. Genetics. 2021; ():1.

Chicago/Turabian Style

Parul Johri; Brian Charlesworth; Emma K Howell; Michael Lynch; Jeffrey D Jensen. 2021. "Revisiting the Notion of Deleterious Sweeps." Genetics , no. : 1.

Review
Published: 09 June 2021 in Viruses
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Human cytomegalovirus (HCMV), one of the most prevalent viruses across the globe, is a common cause of morbidity and mortality for immunocompromised individuals. Recent clinical observations have demonstrated that mixed strain infections are common and may lead to more severe disease progression. This clinical observation illustrates the complexity of the HCMV genome and emphasizes the importance of taking a population-level view of genotypic evolution. Here we review frequently sampled polymorphisms in the glycoproteins of HCMV, comparing the variable regions, and summarizing their corresponding geographic distributions observed to date. The related strain-specific immunity, including neutralization activity and antigen-specific cellular immunity, is also discussed. Given that these glycoproteins are common targets for vaccine design and anti-viral therapies, this observed genetic variation represents an important resource for future efforts to combat HCMV infections.

ACS Style

Hsuan-Yuan Wang; Sarah Valencia; Susanne Pfeifer; Jeffrey Jensen; Timothy Kowalik; Sallie Permar. Common Polymorphisms in the Glycoproteins of Human Cytomegalovirus and Associated Strain-Specific Immunity. Viruses 2021, 13, 1106 .

AMA Style

Hsuan-Yuan Wang, Sarah Valencia, Susanne Pfeifer, Jeffrey Jensen, Timothy Kowalik, Sallie Permar. Common Polymorphisms in the Glycoproteins of Human Cytomegalovirus and Associated Strain-Specific Immunity. Viruses. 2021; 13 (6):1106.

Chicago/Turabian Style

Hsuan-Yuan Wang; Sarah Valencia; Susanne Pfeifer; Jeffrey Jensen; Timothy Kowalik; Sallie Permar. 2021. "Common Polymorphisms in the Glycoproteins of Human Cytomegalovirus and Associated Strain-Specific Immunity." Viruses 13, no. 6: 1106.

Journal article
Published: 29 April 2021 in Cell
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Summary The Cycladic, the Minoan, and the Helladic (Mycenaean) cultures define the Bronze Age (BA) of Greece. Urbanism, complex social structures, craft and agricultural specialization, and the earliest forms of writing characterize this iconic period. We sequenced six Early to Middle BA whole genomes, along with 11 mitochondrial genomes, sampled from the three BA cultures of the Aegean Sea. The Early BA (EBA) genomes are homogeneous and derive most of their ancestry from Neolithic Aegeans, contrary to earlier hypotheses that the Neolithic-EBA cultural transition was due to massive population turnover. EBA Aegeans were shaped by relatively small-scale migration from East of the Aegean, as evidenced by the Caucasus-related ancestry also detected in Anatolians. In contrast, Middle BA (MBA) individuals of northern Greece differ from EBA populations in showing ∼50% Pontic-Caspian Steppe-related ancestry, dated at ca. 2,600-2,000 BCE. Such gene flow events during the MBA contributed toward shaping present-day Greek genomes.

ACS Style

Florian Clemente; Martina Unterländer; Olga Dolgova; Carlos Eduardo G. Amorim; Francisco Coroado-Santos; Samuel Neuenschwander; Elissavet Ganiatsou; Diana I. Cruz Dávalos; Lucas Anchieri; Frédéric Michaud; Laura Winkelbach; Jens Blöcher; Yami Ommar Arizmendi Cárdenas; Bárbara Sousa da Mota; Eleni Kalliga; Angelos Souleles; Ioannis Kontopoulos; Georgia Karamitrou-Mentessidi; Olga Philaniotou; Adamantios Sampson; Dimitra Theodorou; Metaxia Tsipopoulou; Ioannis Akamatis; Paul Halstead; Kostas Kotsakis; Dushka Urem-Kotsou; Diamantis Panagiotopoulos; Christina Ziota; Sevasti Triantaphyllou; Olivier Delaneau; Jeffrey D. Jensen; J. Víctor Moreno-Mayar; Joachim Burger; Vitor C. Sousa; Oscar Lao; Anna-Sapfo Malaspinas; Christina Papageorgopoulou. The genomic history of the Aegean palatial civilizations. Cell 2021, 184, 2565 -2586.e21.

AMA Style

Florian Clemente, Martina Unterländer, Olga Dolgova, Carlos Eduardo G. Amorim, Francisco Coroado-Santos, Samuel Neuenschwander, Elissavet Ganiatsou, Diana I. Cruz Dávalos, Lucas Anchieri, Frédéric Michaud, Laura Winkelbach, Jens Blöcher, Yami Ommar Arizmendi Cárdenas, Bárbara Sousa da Mota, Eleni Kalliga, Angelos Souleles, Ioannis Kontopoulos, Georgia Karamitrou-Mentessidi, Olga Philaniotou, Adamantios Sampson, Dimitra Theodorou, Metaxia Tsipopoulou, Ioannis Akamatis, Paul Halstead, Kostas Kotsakis, Dushka Urem-Kotsou, Diamantis Panagiotopoulos, Christina Ziota, Sevasti Triantaphyllou, Olivier Delaneau, Jeffrey D. Jensen, J. Víctor Moreno-Mayar, Joachim Burger, Vitor C. Sousa, Oscar Lao, Anna-Sapfo Malaspinas, Christina Papageorgopoulou. The genomic history of the Aegean palatial civilizations. Cell. 2021; 184 (10):2565-2586.e21.

Chicago/Turabian Style

Florian Clemente; Martina Unterländer; Olga Dolgova; Carlos Eduardo G. Amorim; Francisco Coroado-Santos; Samuel Neuenschwander; Elissavet Ganiatsou; Diana I. Cruz Dávalos; Lucas Anchieri; Frédéric Michaud; Laura Winkelbach; Jens Blöcher; Yami Ommar Arizmendi Cárdenas; Bárbara Sousa da Mota; Eleni Kalliga; Angelos Souleles; Ioannis Kontopoulos; Georgia Karamitrou-Mentessidi; Olga Philaniotou; Adamantios Sampson; Dimitra Theodorou; Metaxia Tsipopoulou; Ioannis Akamatis; Paul Halstead; Kostas Kotsakis; Dushka Urem-Kotsou; Diamantis Panagiotopoulos; Christina Ziota; Sevasti Triantaphyllou; Olivier Delaneau; Jeffrey D. Jensen; J. Víctor Moreno-Mayar; Joachim Burger; Vitor C. Sousa; Oscar Lao; Anna-Sapfo Malaspinas; Christina Papageorgopoulou. 2021. "The genomic history of the Aegean palatial civilizations." Cell 184, no. 10: 2565-2586.e21.

Journal article
Published: 16 February 2021 in Molecular Biology and Evolution
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Current procedures for inferring population history generally assume complete neutrality—that is, they neglect both direct selection and the effects of selection on linked sites. We here examine how the presence of direct purifying selection and background selection may bias demographic inference by evaluating two commonly-used methods (MSMC and fastsimcoal2), specifically studying how the underlying shape of the distribution of fitness effects and the fraction of directly selected sites interact with demographic parameter estimation. The results show that, even after masking functional genomic regions, background selection may cause the mis-inference of population growth under models of both constant population size and decline. This effect is amplified as the strength of purifying selection and the density of directly selected sites increases, as indicated by the distortion of the site frequency spectrum and levels of nucleotide diversity at linked neutral sites. We also show how simulated changes in background selection effects caused by population size changes can be predicted analytically. We propose a potential method for correcting for the mis-inference of population growth caused by selection. By treating the distribution of fitness effect as a nuisance parameter and averaging across all potential realizations, we demonstrate that even directly selected sites can be used to infer demographic histories with reasonable accuracy.

ACS Style

Parul Johri; Kellen Riall; Hannes Becher; Laurent Excoffier; Brian Charlesworth; Jeffrey D. Jensen. The Impact of Purifying and Background Selection on the Inference of Population History: Problems and Prospects. Molecular Biology and Evolution 2021, 38, 2986 -3003.

AMA Style

Parul Johri, Kellen Riall, Hannes Becher, Laurent Excoffier, Brian Charlesworth, Jeffrey D. Jensen. The Impact of Purifying and Background Selection on the Inference of Population History: Problems and Prospects. Molecular Biology and Evolution. 2021; 38 (7):2986-3003.

Chicago/Turabian Style

Parul Johri; Kellen Riall; Hannes Becher; Laurent Excoffier; Brian Charlesworth; Jeffrey D. Jensen. 2021. "The Impact of Purifying and Background Selection on the Inference of Population History: Problems and Prospects." Molecular Biology and Evolution 38, no. 7: 2986-3003.

Preprint content
Published: 17 November 2020
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It has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations could generate selective sweep-like effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites - both in the presence and absence of interference amongst deleterious mutations - and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious fixations are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of FST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration.

ACS Style

Parul Johri; Brian Charlesworth; Emma K. Howell; Michael Lynch; Jeffrey D. Jensen. Revisiting the Notion of Deleterious Sweeps. 2020, 1 .

AMA Style

Parul Johri, Brian Charlesworth, Emma K. Howell, Michael Lynch, Jeffrey D. Jensen. Revisiting the Notion of Deleterious Sweeps. . 2020; ():1.

Chicago/Turabian Style

Parul Johri; Brian Charlesworth; Emma K. Howell; Michael Lynch; Jeffrey D. Jensen. 2020. "Revisiting the Notion of Deleterious Sweeps." , no. : 1.

Review
Published: 15 October 2020
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ACS Style

Ana Y Morales-Arce; Susanna J Sabin; Anne C Stone; Jeffrey D Jensen. The population genomics of within-host Mycobacterium tuberculosis. 2020, 1 .

AMA Style

Ana Y Morales-Arce, Susanna J Sabin, Anne C Stone, Jeffrey D Jensen. The population genomics of within-host Mycobacterium tuberculosis. . 2020; ():1.

Chicago/Turabian Style

Ana Y Morales-Arce; Susanna J Sabin; Anne C Stone; Jeffrey D Jensen. 2020. "The population genomics of within-host Mycobacterium tuberculosis." , no. : 1.

Perspective
Published: 13 October 2020 in Evolution
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Following widespread infections of the most recent coronavirus known to infect humans, SARS‐CoV‐2, attention has turned to potential therapeutic options. With no drug or vaccine yet approved, one focal point of research is to evaluate the potential value of repurposing existing antiviral treatments, with the logical strategy being to identify at least a short‐term intervention to prevent within‐patient progression, whilst long‐term vaccine strategies unfold. Here, we offer an evolutionary / population‐genetic perspective on one approach that may overwhelm the capacity for pathogen defense (i.e., adaptation) – induced mutational meltdown – providing an overview of key concepts, review of previous theoretical and experimental work of relevance, and guidance for future research. Applied with appropriate care, including target specificity, induced mutational meltdown may provide a general, rapidly implemented approach for the within‐patient eradication of a wide range of pathogens or other undesirable microorganisms. This article is protected by copyright. All rights reserved

ACS Style

Jeffrey D. Jensen; Ryan A. Stikeleather; Timothy F. Kowalik; Michael Lynch. Imposed mutational meltdown as an antiviral strategy. Evolution 2020, 74, 2549 -2559.

AMA Style

Jeffrey D. Jensen, Ryan A. Stikeleather, Timothy F. Kowalik, Michael Lynch. Imposed mutational meltdown as an antiviral strategy. Evolution. 2020; 74 (12):2549-2559.

Chicago/Turabian Style

Jeffrey D. Jensen; Ryan A. Stikeleather; Timothy F. Kowalik; Michael Lynch. 2020. "Imposed mutational meltdown as an antiviral strategy." Evolution 74, no. 12: 2549-2559.

Research article
Published: 01 September 2020 in The American Naturalist
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ACS Style

Matthew R. Jones; L. Scott Mills; Jeffrey D. Jensen; Jeffrey M. Good. The Origin and Spread of Locally Adaptive Seasonal Camouflage in Snowshoe Hares. The American Naturalist 2020, 196, 316 -332.

AMA Style

Matthew R. Jones, L. Scott Mills, Jeffrey D. Jensen, Jeffrey M. Good. The Origin and Spread of Locally Adaptive Seasonal Camouflage in Snowshoe Hares. The American Naturalist. 2020; 196 (3):316-332.

Chicago/Turabian Style

Matthew R. Jones; L. Scott Mills; Jeffrey D. Jensen; Jeffrey M. Good. 2020. "The Origin and Spread of Locally Adaptive Seasonal Camouflage in Snowshoe Hares." The American Naturalist 196, no. 3: 316-332.

Journal article
Published: 12 May 2020 in Genome Biology and Evolution
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First inspired by the seminal work of Lewontin and Krakauer (1973. Distribution of gene frequency as a test of the theory of the selective neutrality of polymorphisms. Genetics 74(1):175–195.) and Maynard Smith and Haigh (1974. The hitch-hiking effect of a favourable gene. Genet Res. 23(1):23–35.), genomic scans for positive selection remain a widely utilized tool in modern population genomic analysis. Yet, the relative frequency and genomic impact of selective sweeps have remained a contentious point in the field for decades, largely owing to an inability to accurately identify their presence and quantify their effects—with current methodologies generally being characterized by low true-positive rates and/or high false-positive rates under many realistic demographic models. Most of these approaches are based on Wright–Fisher assumptions and the Kingman coalescent and generally rely on detecting outlier regions which do not conform to these neutral expectations. However, previous theoretical results have demonstrated that selective sweeps are well characterized by an alternative class of model known as the multiple-merger coalescent. Taken together, this suggests the possibility of not simply identifying regions which reject the Kingman, but rather explicitly testing the relative fit of a genomic window to the multiple-merger coalescent. We describe the advantages of such an approach, which owe to the branching structure differentiating selective and neutral models, and demonstrate improved power under certain demographic scenarios relative to a commonly used approach. However, regions of the demographic parameter space continue to exist in which neither this approach nor existing methodologies have sufficient power to detect selective sweeps.

ACS Style

Rebecca B Harris; Jeffrey D Jensen. Considering Genomic Scans for Selection as Coalescent Model Choice. Genome Biology and Evolution 2020, 12, 871 -877.

AMA Style

Rebecca B Harris, Jeffrey D Jensen. Considering Genomic Scans for Selection as Coalescent Model Choice. Genome Biology and Evolution. 2020; 12 (6):871-877.

Chicago/Turabian Style

Rebecca B Harris; Jeffrey D Jensen. 2020. "Considering Genomic Scans for Selection as Coalescent Model Choice." Genome Biology and Evolution 12, no. 6: 871-877.

Journal article
Published: 01 May 2020 in Genetics
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The relative evolutionary roles of adaptive and non-adaptive processes remain a central question in population genetics. Resolution of this debate has been difficult as an appropriate null model incorporating... The question of the relative evolutionary roles of adaptive and nonadaptive processes has been a central debate in population genetics for nearly a century. While advances have been made in the theoretical development of the underlying models, and statistical methods for estimating their parameters from large-scale genomic data, a framework for an appropriate null model remains elusive. A model incorporating evolutionary processes known to be in constant operation, genetic drift (as modulated by the demographic history of the population) and purifying selection, is lacking. Without such a null model, the role of adaptive processes in shaping within- and between-population variation may not be accurately assessed. Here, we investigate how population size changes and the strength of purifying selection affect patterns of variation at “neutral” sites near functional genomic components. We propose a novel statistical framework for jointly inferring the contribution of the relevant selective and demographic parameters. By means of extensive performance analyses, we quantify the utility of the approach, identify the most important statistics for parameter estimation, and compare the results with existing methods. Finally, we reanalyze genome-wide population-level data from a Zambian population of Drosophila melanogaster, and find that it has experienced a much slower rate of population growth than was inferred when the effects of purifying selection were neglected. Our approach represents an appropriate null model, against which the effects of positive selection can be assessed.

ACS Style

Parul Johri; Brian Charlesworth; Jeffrey D. Jensen. Toward an Evolutionarily Appropriate Null Model: Jointly Inferring Demography and Purifying Selection. Genetics 2020, 215, 173 -192.

AMA Style

Parul Johri, Brian Charlesworth, Jeffrey D. Jensen. Toward an Evolutionarily Appropriate Null Model: Jointly Inferring Demography and Purifying Selection. Genetics. 2020; 215 (1):173-192.

Chicago/Turabian Style

Parul Johri; Brian Charlesworth; Jeffrey D. Jensen. 2020. "Toward an Evolutionarily Appropriate Null Model: Jointly Inferring Demography and Purifying Selection." Genetics 215, no. 1: 173-192.

Preprint content
Published: 29 April 2020
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Current procedures for inferring population history generally assume complete neutrality - that is, they neglect both direct selection and the effects of selection on linked sites. We here examine how the presence of direct purifying selection and background selection may bias demographic inference by evaluating two commonly-used methods (MSMC and fastsimcoal2), specifically studying how the underlying shape of the distribution of fitness effects (DFE) and the fraction of directly selected sites interact with demographic parameter estimation. The results show that, even after masking functional genomic regions, background selection may cause the mis-inference of population growth under models of both constant population size and decline. This effect is amplified as the strength of purifying selection and the density of directly selected sites increases, as indicated by the distortion of the site frequency spectrum and levels of nucleotide diversity at linked neutral sites. We also show how simulated changes in background selection effects caused by population size changes can be predicted analytically. We propose a potential method for correcting for the mis-inference of population growth caused by selection. By treating the DFE as a nuisance parameter and averaging across all potential realizations, we demonstrate that even directly selected sites can be used to infer demographic histories with reasonable accuracy.

ACS Style

Parul Johri; Kellen Riall; Hannes Becher; Laurent Excoffier; Brian Charlesworth; Jeffrey D. Jensen. The impact of purifying and background selection on the inference of population history: problems and prospects. 2020, 1 .

AMA Style

Parul Johri, Kellen Riall, Hannes Becher, Laurent Excoffier, Brian Charlesworth, Jeffrey D. Jensen. The impact of purifying and background selection on the inference of population history: problems and prospects. . 2020; ():1.

Chicago/Turabian Style

Parul Johri; Kellen Riall; Hannes Becher; Laurent Excoffier; Brian Charlesworth; Jeffrey D. Jensen. 2020. "The impact of purifying and background selection on the inference of population history: problems and prospects." , no. : 1.

Original article
Published: 13 April 2020 in Evolution
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Determining how different populations adapt to similar environments is fundamental to understanding the limits of adaptation under changing environments. Snowshoe hares (Lepus americanus) typically molt into white winter coats to remain camouflaged against snow. In some warmer climates, hares have evolved brown winter camouflage—an adaptation that may spread in response to climate change. We used extensive range-wide genomic data to (1) resolve broad patterns of population structure and gene flow and (2) investigate the factors shaping the origins and distribution of winter-brown camouflage variation. In coastal Pacific Northwest (PNW) populations, winter-brown camouflage is known to be determined by a recessive haplotype at the Agouti pigmentation gene. Our phylogeographic analyses revealed deep structure and limited gene flow between PNW and more northern Boreal populations, where winter-brown camouflage is rare along the range edge. Genome sequencing of a winter-brown snowshoe hare from Alaska shows that it lacks the winter-brown PNW haplotype, reflecting a history of convergent phenotypic evolution. However, the PNW haplotype does occur at low frequency in a winter-white population from Montana, consistent with the spread of a locally deleterious recessive variant that is masked from selection when rare. Simulations of this population further show that this masking effect would greatly slow the selective increase of the winter-brown Agouti allele should it suddenly become beneficial (e.g., owing to dramatic declines in snow cover). Our findings underscore how allelic dominance can shape the geographic extent and rate of convergent adaptation in response to rapidly changing environments.

ACS Style

Matthew R. Jones; L. Scott Mills; Jeffrey D. Jensen; Jeffrey M. Good. Convergent evolution of seasonal camouflage in response to reduced snow cover across the snowshoe hare range*. Evolution 2020, 74, 2033 -2045.

AMA Style

Matthew R. Jones, L. Scott Mills, Jeffrey D. Jensen, Jeffrey M. Good. Convergent evolution of seasonal camouflage in response to reduced snow cover across the snowshoe hare range*. Evolution. 2020; 74 (9):2033-2045.

Chicago/Turabian Style

Matthew R. Jones; L. Scott Mills; Jeffrey D. Jensen; Jeffrey M. Good. 2020. "Convergent evolution of seasonal camouflage in response to reduced snow cover across the snowshoe hare range*." Evolution 74, no. 9: 2033-2045.

Comment
Published: 06 April 2020 in Heredity
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Bank C, Renzette N, Liu P, Matuszewski S, Shim H, Foll M, Bolon DN, Zeldovich KB, Kowalik TF, Finberg RW, Wang JP, Jensen JD (2016) An experimental evaluation of drug induced mutational meltdown as an antiviral treatment strategy. Evolution 70:2470–2484 Baranovich T, Wong SS, Armstrong J, Marjuki HJ, Webby RJ, Webster RG, Govorkova EA (2013) T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J Virol 87:3741–3751 Bull JJ, Sanjuan R, Wilke CO (2007) Theory of lethal mutagenesis for viruses. J Virol 81:2930–2939 Dong L, Hu S, Gao J (2020) Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Disco Ther 14:58–60 Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee SF, Barnard DL (2013) Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antivir Res 100:446–454 Li G, De Clercq E (2020) Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov 19:149–150 Lynch M, Burger R, Butcher D, Gabriel W (1993) The mutational meltdown in asexual populations. J Hered 84:339–344 Lynch M, Gabriel W (1990) Mutation load and the survival of small populations. Evolution 44:1725–1737 Matuszewski S, Ormond L, Bank C, Jensen JD (2017) Two sides of the same coin: a population genetics perspective on lethal mutagenesis and mutational meltdown. Virus Evol 3:1–5 Ormond L, Liu P, Matuszewski S, Renzette N, Bank C, Zeldovich K et al. (2017) The combined effect of oseltamivir and favipiravir on influenza A virus evolution. Genome Biol Evol 9:1913–1924 Pénnison S, Singh T, Sniegowski P, Gerrish P (2017) Dynamics and fate of beneficial mutations under lineage contamination by linked deleterious mutations. Genetics 205:1305–1318 Smith EC, Blanc H, Surdel MC, Vugnuzzi M, Denison MR (2013) Coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis: evidence of proofreading and potential therapeutics. PLoS Path 9:e1003565 Download references Correspondence to Jeffrey D. Jensen. The authors declare that they have no conflict of interest. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Jensen, J.D., Lynch, M. Considering mutational meltdown as a potential SARS-CoV-2 treatment strategy. Heredity (2020). https://doi.org/10.1038/s41437-020-0314-z Download citation Received: 01 April 2020 Revised: 02 April 2020 Accepted: 03 April 2020 Published: 06 April 2020 DOI: https://doi.org/10.1038/s41437-020-0314-z

ACS Style

Jeffrey D. Jensen; Michael Lynch. Considering mutational meltdown as a potential SARS-CoV-2 treatment strategy. Heredity 2020, 124, 619 -620.

AMA Style

Jeffrey D. Jensen, Michael Lynch. Considering mutational meltdown as a potential SARS-CoV-2 treatment strategy. Heredity. 2020; 124 (5):619-620.

Chicago/Turabian Style

Jeffrey D. Jensen; Michael Lynch. 2020. "Considering mutational meltdown as a potential SARS-CoV-2 treatment strategy." Heredity 124, no. 5: 619-620.

Brief communication
Published: 31 March 2020 in Evolution
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The within‐host evolutionary dynamics of tuberculosis (TB) remain unclear, and underlying biological characteristics render standard population genetic approaches based upon the Wright‐Fisher model largely inappropriate. In addition, the compact genome combined with an absence of recombination is expected to result in strong purifying selection effects. Thus, it is imperative to establish a biologically‐relevant evolutionary framework incorporating these factors in order to enable an accurate study of this important human pathogen. Further, such a model is critical for inferring fundamental evolutionary parameters related to patient treatment, including mutation rates and the severity of infection bottlenecks. We here implement such a model and infer the underlying evolutionary parameters governing within‐patient evolutionary dynamics. Results demonstrate that the progeny skew associated with the clonal nature of TB severely reduces genetic diversity and that the neglect of this parameter in previous studies has led to significant mis‐inference of mutation rates. As such, our results suggest an underlying de novo mutation rate that is considerably faster than previously inferred, and a progeny distribution differing significantly from Wright‐Fisher assumptions. This inference represents a more appropriate evolutionary null model, against which the periodic effects of positive selection, associated with drug‐resistance for example, may be better assessed. This article is protected by copyright. All rights reserved

ACS Style

Ana Y. Morales‐Arce; Rebecca B. Harris; Anne Stone; Jeffrey D. Jensen. Evaluating the contributions of purifying selection and progeny‐skew in dictating within‐hostMycobacterium tuberculosisevolution. Evolution 2020, 74, 992 -1001.

AMA Style

Ana Y. Morales‐Arce, Rebecca B. Harris, Anne Stone, Jeffrey D. Jensen. Evaluating the contributions of purifying selection and progeny‐skew in dictating within‐hostMycobacterium tuberculosisevolution. Evolution. 2020; 74 (5):992-1001.

Chicago/Turabian Style

Ana Y. Morales‐Arce; Rebecca B. Harris; Anne Stone; Jeffrey D. Jensen. 2020. "Evaluating the contributions of purifying selection and progeny‐skew in dictating within‐hostMycobacterium tuberculosisevolution." Evolution 74, no. 5: 992-1001.

Letters
Published: 24 December 2019 in Proceedings of the National Academy of Sciences
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ACS Style

Jeffrey D. Jensen; Timothy F. Kowalik. A consideration of within-host human cytomegalovirus genetic variation. Proceedings of the National Academy of Sciences 2019, 117, 816 -817.

AMA Style

Jeffrey D. Jensen, Timothy F. Kowalik. A consideration of within-host human cytomegalovirus genetic variation. Proceedings of the National Academy of Sciences. 2019; 117 (2):816-817.

Chicago/Turabian Style

Jeffrey D. Jensen; Timothy F. Kowalik. 2019. "A consideration of within-host human cytomegalovirus genetic variation." Proceedings of the National Academy of Sciences 117, no. 2: 816-817.

Preprint content
Published: 19 December 2019
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The question of the relative evolutionary roles of adaptive and non-adaptive processes has been a central debate in population genetics for nearly a century. While advances have been made in the theoretical development of the underlying models, and statistical methods for estimating their parameters from large-scale genomic data, a framework for an appropriate null model remains elusive. A model incorporating evolutionary processes known to be in constant operation - genetic drift (as modulated by the demographic history of the population) and purifying selection – is lacking. Without such a null model, the role of adaptive processes in shaping within- and between-population variation may not be accurately assessed. Here, we investigate how population size changes and the strength of purifying selection affect patterns of variation at neutral sites near functional genomic components. We propose a novel statistical framework for jointly inferring the contribution of the relevant selective and demographic parameters. By means of extensive performance analyses, we quantify the utility of the approach, identify the most important statistics for parameter estimation, and compare the results with existing methods. Finally, we re-analyze genome-wide population-level data from a Zambian population ofDrosophila melanogaster, and find that it has experienced a much slower rate of population growth than was inferred when the effects of purifying selection were neglected. Our approach represents an appropriate null model, against which the effects of positive selection can be assessed.

ACS Style

Parul Johri; Brian Charlesworth; Jeffrey D. Jensen. Towards an evolutionarily appropriate null model: jointly inferring demography and purifying selection. 2019, 1 .

AMA Style

Parul Johri, Brian Charlesworth, Jeffrey D. Jensen. Towards an evolutionarily appropriate null model: jointly inferring demography and purifying selection. . 2019; ():1.

Chicago/Turabian Style

Parul Johri; Brian Charlesworth; Jeffrey D. Jensen. 2019. "Towards an evolutionarily appropriate null model: jointly inferring demography and purifying selection." , no. : 1.

Preprint content
Published: 29 November 2019 in bioRxiv
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Determining how different populations adapt to similar environments is fundamental to understanding the limits of adaptation under changing environments. Snowshoe hares (Lepus americanus) typically molt into white winter coats to remain camouflaged against snow. In some warmer climates, hares have evolved brown winter camouflage – an adaptation that may spread under climate change. We used extensive range-wide genomic data to 1) resolve broad-scale patterns of population structure and gene flow and 2) investigate the factors shaping the origins and distribution of winter-brown camouflage variation. In coastal Pacific Northwest (PNW) populations, winter-brown camouflage is known to be determined by a recessive haplotype at theAgoutipigmentation gene. Our phylogeographic analyses revealed deep structure and limited gene flow between PNW and more northern Boreal populations, where winter-brown camouflage is rare along the range edge. Genome sequencing of a winter-brown snowshoe hare from Alaska shows that it lacks the winter-brown PNW haplotype, reflecting a history of convergent phenotypic evolution. However, the PNW haplotype does occur at low frequency in a winter-white population from Montana, consistent with the spread of a locally deleterious recessive variant that is masked from selection when rare. Simulations show that if annual snow cover dramatically declined in the same population, then the predicted selective increase in frequency of the now beneficial winter-brownAgoutiallele is likely to be extremely slow due to the same masking effect. Our findings underscore how allelic dominance can shape the geographic extent and rate of convergent adaptation in response to rapidly changing environments.

ACS Style

Matthew R. Jones; L. Scott Mills; Jeffrey D. Jensen; Jeffrey M. Good. Convergent evolution of seasonal camouflage in response to reduced snow cover across the snowshoe hare range. bioRxiv 2019, 851766 .

AMA Style

Matthew R. Jones, L. Scott Mills, Jeffrey D. Jensen, Jeffrey M. Good. Convergent evolution of seasonal camouflage in response to reduced snow cover across the snowshoe hare range. bioRxiv. 2019; ():851766.

Chicago/Turabian Style

Matthew R. Jones; L. Scott Mills; Jeffrey D. Jensen; Jeffrey M. Good. 2019. "Convergent evolution of seasonal camouflage in response to reduced snow cover across the snowshoe hare range." bioRxiv , no. : 851766.

Preprint content
Published: 20 November 2019
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Adaptation is central to population persistence in the face of environmental change, yet we rarely precisely understand the origin and spread of adaptive variation in natural populations. Snowshoe hares (Lepus americanus) along the Pacific Northwest (PNW) coast have evolved brown winter camouflage through positive selection on recessive variation at theAgoutipigmentation gene introgressed from black-tailed jackrabbits (L. californicus). Here we combine new and published whole genome and exome sequences with targeted genotyping ofAgoutiin order to investigate the evolutionary history of local seasonal camouflage adaptation in the PNW. We find evidence of significantly elevated inbreeding and mutational load in coastal winter-brown hares, consistent with a recent range expansion into temperate coastal environments that incurred indirect fitness costs. The genome-wide distribution of introgression tract lengths supports a pulse of hybridization near the end of the last glacial maximum, which may have facilitated range expansion via introgression of winter-brown camouflage variation. However, signatures of a selective sweep atAgoutiindicate a much more recent spread of winter-brown camouflage. Through simulations we show that the temporal lag between the hybrid origin and subsequent selective sweep of the recessive winter-brown allele can be largely attributed to the limits of natural selection imposed by simple allelic dominance. We argue that while hybridization during periods of environmental change may provide a critical reservoir of adaptive variation at range edges, the probability and pace of local adaptation will strongly depend on population demography and the genetic architecture of introgressed variation.

ACS Style

Matthew R. Jones; L. Scott Mills; Jeffrey D. Jensen; Jeffrey M. Good. The origin and spread of locally adaptive seasonal camouflage in snowshoe hares. 2019, 847616 .

AMA Style

Matthew R. Jones, L. Scott Mills, Jeffrey D. Jensen, Jeffrey M. Good. The origin and spread of locally adaptive seasonal camouflage in snowshoe hares. . 2019; ():847616.

Chicago/Turabian Style

Matthew R. Jones; L. Scott Mills; Jeffrey D. Jensen; Jeffrey M. Good. 2019. "The origin and spread of locally adaptive seasonal camouflage in snowshoe hares." , no. : 847616.

Research article
Published: 31 January 2019 in Science
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Adaptive evolution in new or changing environments can be difficult to predict because the functional connections between genotype, phenotype, and fitness are complex. Here, we make these explicit connections by combining field and laboratory experiments in wild mice. We first directly estimate natural selection on pigmentation traits and an underlying pigment locus, Agouti, by using experimental enclosures of mice on different soil colors. Next, we show how a mutation in Agouti associated with survival causes lighter coat color through changes in its protein binding properties. Together, our findings demonstrate how a sequence variant alters phenotype and then reveal the ensuing ecological consequences that drive changes in population allele frequency, thereby illuminating the process of evolution by natural selection.

ACS Style

Rowan D. H. Barrett; Stefan Laurent; Ricardo Mallarino; Susanne P. Pfeifer; Charles C. Y. Xu; Matthieu Foll; Kazumasa Wakamatsu; Jonathan S. Duke-Cohan; Jeffrey D. Jensen; Hopi E. Hoekstra. Linking a mutation to survival in wild mice. Science 2019, 363, 499 -504.

AMA Style

Rowan D. H. Barrett, Stefan Laurent, Ricardo Mallarino, Susanne P. Pfeifer, Charles C. Y. Xu, Matthieu Foll, Kazumasa Wakamatsu, Jonathan S. Duke-Cohan, Jeffrey D. Jensen, Hopi E. Hoekstra. Linking a mutation to survival in wild mice. Science. 2019; 363 (6426):499-504.

Chicago/Turabian Style

Rowan D. H. Barrett; Stefan Laurent; Ricardo Mallarino; Susanne P. Pfeifer; Charles C. Y. Xu; Matthieu Foll; Kazumasa Wakamatsu; Jonathan S. Duke-Cohan; Jeffrey D. Jensen; Hopi E. Hoekstra. 2019. "Linking a mutation to survival in wild mice." Science 363, no. 6426: 499-504.

Journal article
Published: 16 January 2019 in Genetics
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The recent increase in time-series population genomic data from experimental, natural, and ancient populations has been accompanied by a promising growth in methodologies for inferring demographic and selective parameters from such data. However, these methods have largely presumed that the populations of interest are well-described by the Kingman coalescent. In reality, many groups of organisms, including viruses, marine organisms, and some plants, protists, and fungi, typified by high variance in progeny number, may be best characterized by multiple-merger coalescent models. Estimation of population genetic parameters under Wright-Fisher assumptions for these organisms may thus be prone to serious mis-inference. We propose a novel method for the joint inference of demography and selection under the Ψ-coalescent model, termed Multiple-Merger Coalescent Approximate Bayesian Computation, or MMC-ABC. We first demonstrate mis-inference under the Kingman, and then exhibit the superior performance of MMC-ABC under conditions of skewed offspring distributions. In order to highlight the utility of this approach, we reanalyzed previously published drug-selection lines of influenza A virus. We jointly inferred the extent of progeny-skew inherent to viral replication and identified putative drug-resistance mutations.

ACS Style

Andrew M. Sackman; Rebecca B. Harris; Jeffrey D. Jensen. Inferring Demography and Selection in Organisms Characterized by Skewed Offspring Distributions. Genetics 2019, 211, 1019 -1028.

AMA Style

Andrew M. Sackman, Rebecca B. Harris, Jeffrey D. Jensen. Inferring Demography and Selection in Organisms Characterized by Skewed Offspring Distributions. Genetics. 2019; 211 (3):1019-1028.

Chicago/Turabian Style

Andrew M. Sackman; Rebecca B. Harris; Jeffrey D. Jensen. 2019. "Inferring Demography and Selection in Organisms Characterized by Skewed Offspring Distributions." Genetics 211, no. 3: 1019-1028.