71 results on '"Susanne P. Pfeifer"'
Search Results
2. Recommendations for improving statistical inference in population genomics
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Parul Johri, Charles F. Aquadro, Mark Beaumont, Brian Charlesworth, Laurent Excoffier, Adam Eyre-Walker, Peter D. Keightley, Michael Lynch, Gil McVean, Bret A. Payseur, Susanne P. Pfeifer, Wolfgang Stephan, and Jeffrey D. Jensen
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Biology (General) ,QH301-705.5 - Abstract
The field of population genomics has grown rapidly in response to the recent advent of affordable, large-scale sequencing technologies. As opposed to the situation during the majority of the 20th century, in which the development of theoretical and statistical population genetic insights outpaced the generation of data to which they could be applied, genomic data are now being produced at a far greater rate than they can be meaningfully analyzed and interpreted. With this wealth of data has come a tendency to focus on fitting specific (and often rather idiosyncratic) models to data, at the expense of a careful exploration of the range of possible underlying evolutionary processes. For example, the approach of directly investigating models of adaptive evolution in each newly sequenced population or species often neglects the fact that a thorough characterization of ubiquitous nonadaptive processes is a prerequisite for accurate inference. We here describe the perils of these tendencies, present our consensus views on current best practices in population genomic data analysis, and highlight areas of statistical inference and theory that are in need of further attention. Thereby, we argue for the importance of defining a biologically relevant baseline model tuned to the details of each new analysis, of skepticism and scrutiny in interpreting model fitting results, and of carefully defining addressable hypotheses and underlying uncertainties. Genomic data are now being produced at a far greater rate than they can be meaningfully analyzed and interpreted, leading to some questionable use of statistical models. In this Consensus View, the authors provide recommendations for current best practices in population genomic data analysis and highlight areas of statistical inference and theory that are in need of further attention.
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- 2022
3. The third international hackathon for applying insights into large-scale genomic composition to use cases in a wide range of organisms [version 1; peer review: 1 approved, 2 approved with reservations]
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Fawaz Dabbaghie, Divya Kalra, Elbay Aliyev, Wouter De Coster, Kimberley Billingsley, Nicolae Sapoval, Shangzhe Zhang, Gaojianyong Wang, Kimberly Walker, Deepak Choubey, Li Chuin Chong, Alejandro R. Gener, Yilei Fu, Pavel Avdeyev, Ben Busby, Daniel Paiva Agustinho, Sairam Behera, Enrico R. Barrozo, Luis F Paulin, Ahmad Al Khleifat, Susanne P. Pfeifer, Muhammad Sohail Raza, Guangyi Chen, Rebecca Lowdon, Daniela C. Soto, David Molik, Anneri Lötter, Chunhsuan Lo, Suresh Kumar Mendem, Sina Majidian, Damaris Lattimer, Priya Lakra, Bai-Wei Lo, Chia-Sin Liew, Rupesh K. Kesharwani, Maria Jose, Jędrzej Kubica, Sree Rohit Raj Kolora, Wolfram Höps, David Morgan Henke, Michael D. Jochum, Anastasia Illarionova, Fritz J Sedlazeck, Weiyu Zhou, Todd Treangen, Philippe Sanio, Jianzhi Yang, Tiancheng Xu, Ramanandan Prabhakaran, Chi-Lam Poon, Aditi Sammi, Marie Saitou, Hiroko Ohmiya, Rajarshi Mondal, Najeeb Syed, Carolina Peralta, Nasrin Parvin, Timothy Hefferon, and Medhat Mahmoud
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Structural variants ,k-mer ,Covid-19 ,Long-reads ,Tomatoes ,Cancer ,eng ,Medicine ,Science - Abstract
In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.
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- 2022
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4. The Complete Genome Sequence of the Staphylococcus Bacteriophage Metroid
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Adele Crane, Joy Abaidoo, Gabriella Beltran, Danielle Fry, Colleen Furey, Noe Green, Ravneet Johal, Bruno La Rosa, Catalina Lopez Jimenez, Linh Luong, Garett Maag, Jade Porche, Lauren Reyes, Aspen Robinson, Samantha Sabbara, Lucia Soto Herrera, Angelica Urquidez Negrete, Pauline Wilson, Kerry Geiler-Samerotte, and Susanne P. Pfeifer
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bacteriophage ,myoviridae ,de novo assembly ,gene annotation ,Genetics ,QH426-470 - Abstract
Phages infecting bacteria of the genus Staphylococcus play an important role in their host’s ecology and evolution. On one hand, horizontal gene transfer from phage can encourage the rapid adaptation of pathogenic Staphylococcus enabling them to escape host immunity or access novel environments. On the other hand, lytic phages are promising agents for the treatment of bacterial infections, especially those resistant to antibiotics. As part of an ongoing effort to gain novel insights into bacteriophage diversity, we characterized the complete genome of the Staphylococcus bacteriophage Metroid, a cluster C phage with a genome size of 151kb, encompassing 254 predicted protein-coding genes as well as 4 tRNAs. A comparative genomic analysis highlights strong similarities – including a conservation of the lysis cassette – with other Staphylococcus cluster C bacteriophages, several of which were previously characterized for therapeutic applications.
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- 2020
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5. Microbacterium Cluster EA Bacteriophages: Phylogenomic Relationships and Host Range Predictions
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Mark Milhaven, Cyril J. Versoza, Aman Garg, Lindsey Cai, Sanjana Cherian, Kamalei Johnson, Kevin Salas Perez, Madison Blanco, Jackelyn Lobatos, Corinne Mitra, Maria Strasser, and Susanne P. Pfeifer
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bacteriophage ,cluster EA ,comparative genomics ,host range ,Biology (General) ,QH301-705.5 - Abstract
Bacteriophages are being widely harnessed as an alternative to antibiotics due to the global emergence of drug-resistant pathogens. To guide the usage of these bactericidal agents, characterization of their host specificity is vital—however, host range information remains limited for many bacteriophages. This is particularly the case for bacteriophages infecting the Microbacterium genus, despite their importance in agriculture, biomedicine, and biotechnology. Here, we elucidate the phylogenomic relationships between 125 Microbacterium cluster EA bacteriophages—including members from 11 sub-clusters (EA1 to EA11)—and infer their putative host ranges using insights from codon usage bias patterns as well as predictions from both exploratory and confirmatory computational methods. Our computational analyses suggest that cluster EA bacteriophages have a shared infection history across the Microbacterium clade. Interestingly, bacteriophages of all sub-clusters exhibit codon usage preference patterns that resemble those of bacterial strains different from ones used for isolation, suggesting that they might be able to infect additional hosts. Furthermore, host range predictions indicate that certain sub-clusters may be better suited in prospective biotechnological and medical applications such as phage therapy.
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- 2023
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6. Comparative Genomics of Closely-Related Gordonia Cluster DR Bacteriophages
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Cyril J. Versoza, Abigail A. Howell, Tanya Aftab, Madison Blanco, Akarshi Brar, Elaine Chaffee, Nicholas Howell, Willow Leach, Jackelyn Lobatos, Michael Luca, Meghna Maddineni, Ruchira Mirji, Corinne Mitra, Maria Strasser, Saige Munig, Zeel Patel, Minerva So, Makena Sy, Sarah Weiss, and Susanne P. Pfeifer
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bacteriophage ,cluster DR ,Gordonia ,comparative genomics ,host range ,Microbiology ,QR1-502 - Abstract
Bacteriophages infecting bacteria of the genus Gordonia have increasingly gained interest in the scientific community for their diverse applications in agriculture, biotechnology, and medicine, ranging from biocontrol agents in wastewater management to the treatment of opportunistic pathogens in pulmonary disease patients. However, due to the time and costs associated with experimental isolation and cultivation, host ranges for many bacteriophages remain poorly characterized, hindering a more efficient usage of bacteriophages in these areas. Here, we perform a series of computational genomic inferences to predict the putative host ranges of all Gordonia cluster DR bacteriophages known to date. Our analyses suggest that BiggityBass (as well as several of its close relatives) is likely able to infect host bacteria from a wide range of genera—from Gordonia to Nocardia to Rhodococcus, making it a suitable candidate for future phage therapy and wastewater treatment strategies.
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- 2022
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7. Computational Prediction of Bacteriophage Host Ranges
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Cyril J. Versoza and Susanne P. Pfeifer
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bacteriophages ,bacterial hosts ,bioinformatic tools ,host ranges ,Biology (General) ,QH301-705.5 - Abstract
Increased antibiotic resistance has prompted the development of bacteriophage agents for a multitude of applications in agriculture, biotechnology, and medicine. A key factor in the choice of agents for these applications is the host range of a bacteriophage, i.e., the bacterial genera, species, and strains a bacteriophage is able to infect. Although experimental explorations of host ranges remain the gold standard, such investigations are inherently limited to a small number of viruses and bacteria amendable to cultivation. Here, we review recently developed bioinformatic tools that offer a promising and high-throughput alternative by computationally predicting the putative host ranges of bacteriophages, including those challenging to grow in laboratory environments.
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- 2022
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8. Common Polymorphisms in the Glycoproteins of Human Cytomegalovirus and Associated Strain-Specific Immunity
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Hsuan-Yuan Wang, Sarah M. Valencia, Susanne P. Pfeifer, Jeffrey D. Jensen, Timothy F. Kowalik, and Sallie R. Permar
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human cytomegalovirus ,glycoprotein ,polymorphism ,genotype ,strain-specific immunity ,Microbiology ,QR1-502 - Abstract
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.
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- 2021
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9. On the Demographic and Selective Forces Shaping Patterns of Human Cytomegalovirus Variation within Hosts
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Andrew M. Sackman, Susanne P. Pfeifer, Timothy F. Kowalik, and Jeffrey D. Jensen
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human cytomegalovirus ,population genetics ,viral evolution ,Medicine - Abstract
Human cytomegalovirus (HCMV) is a member of the β -herpesvirus subfamily within Herpesviridae that is nearly ubiquitous in human populations, and infection generally results only in mild symptoms. However, symptoms can be severe in immunonaive individuals, and transplacental congenital infection of HCMV can result in serious neurological sequelae. Recent work has revealed much about the demographic and selective forces shaping the evolution of congenitally transmitted HCMV both on the level of hosts and within host compartments, providing insight into the dynamics of congenital infection, reinfection, and evolution of HCMV with important implications for the development of effective treatments and vaccines.
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- 2018
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10. The third international hackathon for applying insights into large-scale genomic composition to use cases in a wide range of organisms [version 1; peer review: 1 approved, 3 approved with reservations]
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Kimberly Walker, Divya Kalra, Rebecca Lowdon, Guangyi Chen, David Molik, Daniela C. Soto, Fawaz Dabbaghie, Ahmad Al Khleifat, Medhat Mahmoud, Luis F Paulin, Muhammad Sohail Raza, Susanne P. Pfeifer, Daniel Paiva Agustinho, Elbay Aliyev, Pavel Avdeyev, Enrico R. Barrozo, Sairam Behera, Kimberley Billingsley, Li Chuin Chong, Deepak Choubey, Wouter De Coster, Yilei Fu, Alejandro R. Gener, Timothy Hefferon, David Morgan Henke, Wolfram Höps, Anastasia Illarionova, Michael D. Jochum, Maria Jose, Rupesh K. Kesharwani, Sree Rohit Raj Kolora, Jędrzej Kubica, Priya Lakra, Damaris Lattimer, Chia-Sin Liew, Bai-Wei Lo, Chunhsuan Lo, Anneri Lötter, Sina Majidian, Suresh Kumar Mendem, Rajarshi Mondal, Hiroko Ohmiya, Nasrin Parvin, Carolina Peralta, Chi-Lam Poon, Ramanandan Prabhakaran, Marie Saitou, Aditi Sammi, Philippe Sanio, Nicolae Sapoval, Najeeb Syed, Todd Treangen, Gaojianyong Wang, Tiancheng Xu, Jianzhi Yang, Shangzhe Zhang, Weiyu Zhou, Fritz J Sedlazeck, and Ben Busby
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Software Tool Article ,Articles ,Structural variants ,k-mer ,Covid-19 ,Long-reads ,Tomatoes ,Cancer ,Viral integration ,Hackathon ,NGS - Abstract
In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.
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- 2022
- Full Text
- View/download PDF
11. Performance evaluation of six popular short-read simulators
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Mark Milhaven and Susanne P. Pfeifer
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Genetics ,Genetics (clinical) - Abstract
High-throughput sequencing data enables the comprehensive study of genomes and the variation therein. Essential for the interpretation of this genomic data is a thorough understanding of the computational methods used for processing and analysis. Whereas “gold-standard” empirical datasets exist for this purpose in humans, synthetic (i.e., simulated) sequencing data can offer important insights into the capabilities and limitations of computational pipelines for any arbitrary species and/or study design—yet, the ability of read simulator software to emulate genomic characteristics of empirical datasets remains poorly understood. We here compare the performance of six popular short-read simulators—ART, DWGSIM, InSilicoSeq, Mason, NEAT, and wgsim—and discuss important considerations for selecting suitable models for benchmarking.
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- 2022
12. Developing an Evolutionary Baseline Model for Humans: Jointly Inferring Purifying Selection with Population History
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Parul Johri, Susanne P Pfeifer, and Jeffrey D Jensen
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Genetics ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics - Abstract
Building evolutionarily appropriate baseline models for natural populations is not only important for answering fundamental questions in population genetics – including quantifying the relative contributions of adaptive vs. non-adaptive processes – but it is also essential for identifying candidate loci experiencing relatively rare and episodic forms of selection (e.g.,positive or balancing selection). Here, a baseline model was developed for a human population of West African ancestry, the Yoruba, comprising processes constantly operating on the genome (i.e., purifying and background selection, population size changes, recombination rate heterogeneity, and gene conversion). Specifically, to perform joint inference of selective effects with demography, an approximate Bayesian approach was employed that utilizes the decay of background selection effects around functional elements, taking into account genomic architecture. This approach inferred a recent 6-fold population growth together with a distribution of fitness effects that is skewed towards effectively neutral mutations. Importantly, these results further suggest that, while strong and/or frequent recurrent positive selection is inconsistent with observed data, weak to moderate positive selection is consistent but unidentifiable if rare.
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- 2023
13. Protective effect of pre-existing natural immunity in a nonhuman primate reinfection model of congenital cytomegalovirus infection
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Matilda Moström, Shan Yu, Dollnovan Tran, Frances Saccoccio, Cyril J. Versoza, Daniel Malouli, Anne Mirza, Sarah Valencia, Margaret Gilbert, Robert Blair, Scott Hansen, Peter Barry, Klaus Früh, Jeffrey D. Jensen, Susanne P. Pfeifer, Timothy F. Kowalik, Sallie R. Permar, and Amitinder Kaur
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Congenital cytomegalovirus (cCMV) is the leading infectious cause of neurologic defects in newborns with particularly severe sequelae in the setting of primary CMV infection in the first trimester of pregnancy. The majority of cCMV cases worldwide occur after non-primary infection in CMV-seropositive women; yet the extent to which pre-existing natural CMV-specific immunity protects against CMV reinfection or reactivation during pregnancy remains ill-defined. We previously reported on a novel nonhuman primate model of cCMV in rhesus macaques where 100% placental transmission and 83% fetal loss were seen in CD4+T lymphocyte-depleted rhesus CMV (RhCMV)-seronegative dams after primary RhCMV infection. To investigate the protective effect of preconception maternal immunity, we performed reinfection studies in CD4+ T lymphocyte-depleted RhCMV-seropositive dams inoculated in late first / early second trimester gestation with RhCMV strains 180.92 (n=2), or RhCMV UCD52 and FL-RhCMVΔRh13.1/SIVgag, a wild-type-like RhCMV clone with SIVgaginserted as an immunological marker (n=3). An early transient increase in circulating monocytes followed by boosting of the pre-existing RhCMV-specific CD8+ T lymphocyte and antibody response was observed in the reinfected dams but not in control CD4+ T lymphocyte-depleted dams. Emergence of SIV Gag-specific CD8+ T lymphocyte responses in macaques inoculated with the FL-RhCMVΔRh13.1/SIVgagvirus confirmed reinfection. Placental transmission was detected in only one of five reinfected dams and there were no adverse fetal sequelae. Viral whole genome, short-read, deep sequencing analysis confirmed transmission of both reinfection RhCMV strains across the placenta with ∼30% corresponding to FL-RhCMVΔRh13.1/SIVgagand ∼70% to RhCMV UCD52, consistent with the mixed human CMV infections reported in infants with cCMV. Our data showing reduced placental transmission and absence of fetal loss after non-primary as opposed to primary infection in CD4+ T lymphocyte-depleted dams indicates that preconception maternal CMV-specific CD8+ T lymphocyte and/or humoral immunity can protect against cCMV infection.Author SummaryGlobally, pregnancies in CMV-seropositive women account for the majority of cases of congenital CMV infection but the immune responses needed for protection against placental transmission in mothers with non-primary infection remains unknown. Recently, we developed a nonhuman primate model of primary rhesus CMV (RhCMV) infection in which placental transmission and fetal loss occurred in RhCMV-seronegative CD4+ T lymphocyte-depleted macaques. By conducting similar studies in RhCMV-seropositive dams, we demonstrated the protective effect of pre-existing natural CMV-specific CD8+ T lymphocytes and humoral immunity against congenital CMV after reinfection. A 5-fold reduction in congenital transmission and complete protection against fetal loss was observed in dams with pre-existing immunity compared to primary CMV in this model. Our study is the first formal demonstration in a relevant model of human congenital CMV that natural pre-existing CMV-specific maternal immunity can limit congenital CMV transmission and its sequelae. The nonhuman primate model of non-primary congenital CMV will be especially relevant to studying immune requirements of a maternal vaccine for women in high CMV seroprevalence areas at risk of repeated CMV reinfections during pregnancy.
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- 2023
14. Developing an Appropriate Evolutionary Baseline Model for the Study of Human Cytomegalovirus
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Abigail A Howell, John W Terbot, Vivak Soni, Parul Johri, Jeffrey D Jensen, and Susanne P Pfeifer
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Genetics ,Ecology, Evolution, Behavior and Systematics - Abstract
Human cytomegalovirus (HCMV) represents a major threat to human health, contributing to both birth defects in neonates as well as organ transplant failure and opportunistic infections in immunocompromised individuals. HCMV exhibits considerable interhost and intrahost diversity, which likely influences the pathogenicity of the virus. Therefore, understanding the relative contributions of various evolutionary forces in shaping patterns of variation is of critical importance both mechanistically and clinically. Herein, we present the individual components of an evolutionary baseline model for HCMV, with a particular focus on congenital infections for the sake of illustration—including mutation and recombination rates, the distribution of fitness effects, infection dynamics, and compartmentalization—and describe the current state of knowledge of each. By building this baseline model, researchers will be able to better describe the range of possible evolutionary scenarios contributing to observed variation as well as improve power and reduce false-positive rates when scanning for adaptive mutations in the HCMV genome.
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- 2023
15. Complete Genome Sequence of the Microbacterium Bacteriophage Chako
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Mark Milhaven, Lindsey Cai, Sanjana Cherian, Kamalei Johnson, Kevin Salas Perez, Madison Blanco, Aman Garg, Jackelyn Lobatos, Corinne Mitra, Maria Strasser, Robert Harms, and Susanne P. Pfeifer
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Immunology and Microbiology (miscellaneous) ,Genetics ,Molecular Biology - Abstract
We characterized the complete genome sequence of Chako, an obligate lytic bacteriophage with siphovirus morphology from subcluster EA1 that infects Microbacterium foliorum NRRL B-24224. Its 41.6-kb genome contains 62 putative protein-coding genes and is highly similar to that of bacteriophage HanSolo (99.26% nucleotide identity).
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- 2023
16. The Impact of Sample Size and Population History on Observed Mutational Spectra: A Case Study in Human and Chimpanzee Populations
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Suhail Ghafoor, João Santos, Cyril J Versoza, Jeffrey D Jensen, and Susanne P Pfeifer
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Genetics ,Ecology, Evolution, Behavior and Systematics - Abstract
Recent studies have highlighted variation in the mutational spectra among human populations as well as closely related hominoids—yet little remains known about the genetic and nongenetic factors driving these rate changes across the genome. Pinpointing the root causes of these differences is an important endeavor that requires careful comparative analyses of population-specific mutational landscapes at both broad and fine genomic scales. However, several factors can confound such analyses. Although previous studies have shown that technical artifacts, such as sequencing errors and batch effects, can contribute to observed mutational shifts, other potentially confounding parameters have received less attention thus far. Using population genetic simulations of human and chimpanzee populations as an illustrative example, we here show that the sample size required for robust inference of mutational spectra depends on the population-specific demographic history. As a consequence, the power to detect rate changes is high in certain hominoid populations while, for others, currently available sample sizes preclude analyses at fine genomic scales.
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- 2023
17. Complete Genome Sequence of the Cluster P Mycobacteriophage Phegasus
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Abigail A. Howell, Cyril J. Versoza, Gabriella Cerna, Tyler Johnston, Shriya Kakde, Keith Karuku, Maria Kowal, Jasmine Monahan, Jillian Murray, Teresa Nguyen, Aurely Sanchez Carreon, Elizabeth Song, Abigail Streiff, Blake Su, Faith Youkhana, Saige Munig, Zeel Patel, Minerva So, Makena Sy, Sarah Weiss, Yang Zhou, and Susanne P. Pfeifer
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Immunology and Microbiology (miscellaneous) ,Genetics ,Molecular Biology - Abstract
We characterized the complete genome of the cluster P mycobacteriophage Phegasus. Its 47.5-kb genome contains 81 protein-coding genes, 36 of which could be assigned a putative function. Phegasus is most closely related to two subcluster P1 bacteriophages, Mangethe and Majeke, with an average nucleotide identity of 99.63% each.
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- 2022
18. Complete Genome Sequence of the Gordonia Bacteriophage BiggityBass
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Cyril J. Versoza, Abigail A. Howell, Tanya Aftab, Madison Blanco, Akarshi Brar, Elaine Chaffee, Nicholas Howell, Willow Leach, Jackelyn Lobatos, Michael Luca, Meghna Maddineni, Ruchira Mirji, Corinne Mitra, Maria Strasser, Saige Munig, Zeel Patel, Minerva So, Makena Sy, Sarah Weiss, Christopher D. Herren, Martha Smith Caldas, and Susanne P. Pfeifer
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Immunology and Microbiology (miscellaneous) ,Genetics ,Molecular Biology - Abstract
Here, we characterized the complete genome of the Siphoviridae BiggityBass, a lytic subcluster DR bacteriophage infecting Gordonia terrae CAG3. Its 63.2-kb genome contains 84 protein-coding genes, of which 40 could be assigned a putative function. BiggityBass is related most closely to AnClar and Yago84 with 90.61% and 90.52% nucleotide identity, respectively.
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- 2022
19. Phylogenomic analyses and host range prediction of cluster P mycobacteriophages
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Abigail A Howell, Cyril J Versoza, Gabriella Cerna, Tyler Johnston, Shriya Kakde, Keith Karuku, Maria Kowal, Jasmine Monahan, Jillian Murray, Teresa Nguyen, Aurely Sanchez Carreon, Abigail Streiff, Blake Su, Faith Youkhana, Saige Munig, Zeel Patel, Minerva So, Makena Sy, Sarah Weiss, and Susanne P Pfeifer
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Genetics ,Humans ,Bacteriophages ,Mycobacteriophages ,Genome, Viral ,Molecular Biology ,Phylogeny ,Host Specificity ,Genetics (clinical) - Abstract
Bacteriophages, infecting bacterial hosts in every environment on our planet, are a driver of adaptive evolution in bacterial communities. At the same time, the host range of many bacteriophages—and thus one of the selective pressures acting on complex microbial systems in nature—remains poorly characterized. Here, we computationally inferred the putative host ranges of 40 cluster P mycobacteriophages, including members from 6 subclusters (P1–P6). A series of comparative genomic analyses revealed that mycobacteriophages of subcluster P1 are restricted to the Mycobacterium genus, whereas mycobacteriophages of subclusters P2–P6 are likely also able to infect other genera, several of which are commonly associated with human disease. Further genomic analysis highlighted that the majority of cluster P mycobacteriophages harbor a conserved integration-dependent immunity system, hypothesized to be the ancestral state of a genetic switch that controls the shift between lytic and lysogenic life cycles—a temperate characteristic that impedes their usage in antibacterial applications.
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- 2022
20. Developing an appropriate evolutionary baseline model for the study of SARS-CoV-2 patient samples
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John W. Terbot, Parul Johri, Schuyler W. Liphardt, Vivak Soni, Susanne P. Pfeifer, Brandon S. Cooper, Jeffrey M. Good, and Jeffrey D. Jensen
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Virology ,Immunology ,Genetics ,Parasitology ,Molecular Biology ,Microbiology - Abstract
Over the past 3 years, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread through human populations in several waves, resulting in a global health crisis. In response, genomic surveillance efforts have proliferated in the hopes of tracking and anticipating the evolution of this virus, resulting in millions of patient isolates now being available in public databases. Yet, while there is a tremendous focus on identifying newly emerging adaptive viral variants, this quantification is far from trivial. Specifically, multiple co-occurring and interacting evolutionary processes are constantly in operation and must be jointly considered and modeled in order to perform accurate inference. We here outline critical individual components of such an evolutionary baseline model—mutation rates, recombination rates, the distribution of fitness effects, infection dynamics, and compartmentalization—and describe the current state of knowledge pertaining to the related parameters of each in SARS-CoV-2. We close with a series of recommendations for future clinical sampling, model construction, and statistical analysis.
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- 2023
21. The impact of frequently neglected model violations on bacterial recombination rate estimation: a case study inMycobacterium canettiiandMycobacterium tuberculosis
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Susanna Sabin, Ana Y Morales-Arce, Susanne P Pfeifer, and Jeffrey D Jensen
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Recombination, Genetic ,Genetics ,Humans ,Tuberculosis ,Mycobacterium tuberculosis ,Molecular Biology ,Genome, Bacterial ,Phylogeny ,Genetics (clinical) ,Mycobacterium - Abstract
Mycobacterium canettii is a causative agent of tuberculosis in humans, along with the members of the Mycobacterium tuberculosis complex. Frequently used as an outgroup to the M. tuberculosis complex in phylogenetic analyses, M. canettii is thought to offer the best proxy for the progenitor species that gave rise to the complex. Here, we leverage whole-genome sequencing data and biologically relevant population genomic models to compare the evolutionary dynamics driving variation in the recombining M. canettii with that in the nonrecombining M. tuberculosis complex, and discuss differences in observed genomic diversity in the light of expected levels of Hill–Robertson interference. In doing so, we highlight the methodological challenges of estimating recombination rates through traditional population genetic approaches using sequences called from populations of microorganisms and evaluate the likely mis-inference that arises owing to a neglect of common model violations including purifying selection, background selection, progeny skew, and population size change. In addition, we compare performance when full within-host polymorphism data are utilized, versus the more common approach of basing analyses on within-host consensus sequences.
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- 2022
22. The Complete Genome Sequence of the Staphylococcus Bacteriophage Metroid
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Bruno La Rosa, Garett Maag, Pauline Wilson, Adele Crane, Lauren Reyes, Linh B. Luong, Lucia Soto Herrera, Gabriella Beltran, Noe Green, Danielle Fry, Catalina Lopez Jimenez, Kerry Geiler-Samerotte, Joy Abaidoo, Angelica Urquidez Negrete, Colleen Furey, Jade Porche, Susanne P. Pfeifer, Samantha Sabbara, Aspen Robinson, and Ravneet Johal
- Subjects
Myoviridae ,de novo assembly ,QH426-470 ,medicine.disease_cause ,Genome ,Bacteriophage ,03 medical and health sciences ,bacteriophage ,medicine ,Genetics ,Molecular Biology ,Genome size ,Gene ,Genetics (clinical) ,030304 developmental biology ,Whole genome sequencing ,0303 health sciences ,biology ,030306 microbiology ,biology.organism_classification ,gene annotation ,Lytic cycle ,Horizontal gene transfer ,myoviridae ,Staphylococcus - Abstract
Phages infecting bacteria of the genus Staphylococcus play an important role in their host’s ecology and evolution. On one hand, horizontal gene transfer from phage can encourage the rapid adaptation of pathogenic Staphylococcus enabling them to escape host immunity or access novel environments. On the other hand, lytic phages are promising agents for the treatment of bacterial infections, especially those resistant to antibiotics. As part of an ongoing effort to gain novel insights into bacteriophage diversity, we characterized the complete genome of the Staphylococcus bacteriophage Metroid, a cluster C phage with a genome size of 151kb, encompassing 254 predicted protein-coding genes as well as 4 tRNAs. A comparative genomic analysis highlights strong similarities – including a conservation of the lysis cassette – with other Staphylococcus cluster C1 bacteriophages, several of which were previously characterized for therapeutic applications.
- Published
- 2020
23. A Fine-Scale Genetic Map for Vervet Monkeys
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Susanne P. Pfeifer
- Subjects
Male ,Recombination, Genetic ,education.field_of_study ,Genome ,biology ,Phylogenetic tree ,Population ,Background selection ,biology.organism_classification ,Polymorphism, Single Nucleotide ,Variation (linguistics) ,Order (biology) ,Evolutionary biology ,Chlorocebus aethiops ,Genetics ,Animals ,Humans ,Fast Track ,Female ,Vervet monkey ,education ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Recombination - Abstract
Despite its important biological role, the evolution of recombination rates remains relatively poorly characterized. This owes, in part, to the lack of high-quality genomic resources to address this question across diverse species. Humans and our closest evolutionary relatives, anthropoid apes, have remained a major focus of large-scale sequencing efforts, and thus recombination rate variation has been comparatively well studied in this group—with earlier work revealing a conservation at the broad- but not the fine-scale. However, in order to better understand the nature of this variation, and the time scales on which substantial modifications occur, it is necessary to take a broader phylogenetic perspective. I here present the first fine-scale genetic map for vervet monkeys based on whole-genome population genetic data from ten individuals and perform a series of comparative analyses with the great apes. The results reveal a number of striking features. First, owing to strong positive correlations with diversity and weak negative correlations with divergence, analyses suggest a dominant role for purifying and background selection in shaping patterns of variation in this species. Second, results support a generally reduced broad-scale recombination rate compared with the great apes, as well as a narrower fraction of the genome in which the majority of recombination events are observed to occur. Taken together, this data set highlights the great necessity of future research to identify genomic features and quantify evolutionary processes that are driving these rate changes across primates.
- Published
- 2020
24. The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates
- Author
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Lucie A Bergeron, Søren Besenbacher, Tychele Turner, Cyril J Versoza, Richard J Wang, Alivia Lee Price, Ellie Armstrong, Meritxell Riera, Jedidiah Carlson, Hwei-yen Chen, Matthew W Hahn, Kelley Harris, April Snøfrid Kleppe, Elora H López-Nandam, Priya Moorjani, Susanne P Pfeifer, George P Tiley, Anne D Yoder, Guojie Zhang, and Mikkel H Schierup
- Subjects
General Immunology and Microbiology ,QH301-705.5 ,Science ,General Neuroscience ,pedigree-based estimation ,General Medicine ,Reference Standards ,ngs analysis ,Macaca mulatta ,General Biochemistry, Genetics and Molecular Biology ,Pedigree ,computational pipeline ,Germ Cells ,Genetic Techniques ,Mutation Rate ,Medicine ,Animals ,Biology (General) ,Laboratories ,Germ-Line Mutation - Abstract
In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various nonhuman species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and appropriately accounting for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a ‘Mutationathon,’ a competition organized among five research labs to compare germline mutation rate estimates for a single pedigree of rhesus macaques. We report almost a twofold variation in the final estimated rate among groups using different post-alignment processing, calling, and filtering criteria, and provide details into the sources of variation across studies. Though the difference among estimates is not statistically significant, this discrepancy emphasizes the need for standardized methods in mutation rate estimations and the difficulty in comparing rates from different studies. Finally, this work aims to provide guidelines for computational and statistical benchmarks for future studies interested in identifying germline mutations from pedigrees.
- Published
- 2022
25. Author response: The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates
- Author
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Lucie A Bergeron, Søren Besenbacher, Tychele Turner, Cyril J Versoza, Richard J Wang, Alivia Lee Price, Ellie Armstrong, Meritxell Riera, Jedidiah Carlson, Hwei-yen Chen, Matthew W Hahn, Kelley Harris, April Snøfrid Kleppe, Elora H López-Nandam, Priya Moorjani, Susanne P Pfeifer, George P Tiley, Anne D Yoder, Guojie Zhang, and Mikkel H Schierup
- Published
- 2022
26. Recommendations for improving statistical inference in population genomics
- Author
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Michael Lynch, Mark A. Beaumont, Adam Eyre-Walker, Brian Charlesworth, Charles F. Aquadro, Bret A. Payseur, Susanne P. Pfeifer, Wolfgang Stephan, Jeffrey D. Jensen, Peter D. Keightley, Parul Johri, Laurent Excoffier, and Gil McVean
- Subjects
education.field_of_study ,Scrutiny ,General Immunology and Microbiology ,Computer science ,General Neuroscience ,Best practice ,media_common.quotation_subject ,Population ,Inference ,Genomics ,Data science ,General Biochemistry, Genetics and Molecular Biology ,Field (computer science) ,Population genomics ,Statistical inference ,570 Life sciences ,biology ,Metagenomics ,General Agricultural and Biological Sciences ,education ,Skepticism ,media_common - Abstract
AU The:field Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly of population genomics has grown rapidly in response : to the recent advent of affordable, large-scale sequencing technologies. As opposed to the situation during the majority of the 20th century, in which the development of theoretical and statistical population genetic insights outpaced the generation of data to which they could be applied, genomic data are now being produced at a far greater rate than they can be meaningfully analyzed and interpreted. With this wealth of data has come a tendency to focus on fitting specific (and often rather idiosyncratic) models to data, at the expense of a careful exploration of the range of possible underlying evolutionary processes. For example, the approach of directly investigating models of adaptive evolution in each newly sequenced population or species often neglects the fact that a thorough characterization of ubiquitous nonadaptive processes is a prerequisite for accurate inference. We here describe the perils of these tendencies, present our consensus views on current best practices in population genomic data analysis, and highlight areas of statistical inference and theory that are in need of further attention. Thereby, we argue for the importance of defining a biologically relevant baseline model tuned to the details of each new analysis, of skepticism and scrutiny in interpreting model fitting results, and of carefully defining addressable hypotheses and underlying uncertainties.
- Published
- 2022
- Full Text
- View/download PDF
27. Recent population genomic insights into the genetic basis of arsenic tolerance in humans: the difficulties of identifying positively selected loci in strongly bottlenecked populations
- Author
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Mario Apata and Susanne P. Pfeifer
- Subjects
0301 basic medicine ,Population genetics ,Demographic history ,Population ,Review Article ,010501 environmental sciences ,Biology ,01 natural sciences ,Evolutionary genetics ,Arsenic ,03 medical and health sciences ,Gene Frequency ,Genetic drift ,Genetic variation ,Genetics ,Humans ,Selection, Genetic ,Indigenous Peoples ,education ,Genetics (clinical) ,0105 earth and related environmental sciences ,education.field_of_study ,Natural selection ,Population size ,Genetic Drift ,South America ,Adaptation, Physiological ,Founder Effect ,Lactase persistence ,Genetics, Population ,Phenotype ,030104 developmental biology ,Population bottleneck ,Evolutionary biology - Abstract
Recent advances in genomics have enabled researchers to shed light on the evolutionary processes driving human adaptation, by revealing the genetic architectures underlying traits ranging from lactase persistence, to skin pigmentation, to hypoxic response, to arsenic tolerance. Complicating the identification of targets of positive selection in modern human populations is their complex demographic history, characterized by population bottlenecks and expansions, population structure, migration, and admixture. In particular, founder effects and recent strong population size reductions, such as those experienced by the indigenous peoples of the Americas, have severe impacts on genetic variation that can lead to the accumulation of large allele frequency differences between populations due to genetic drift rather than natural selection. While distinguishing the effects of demographic history from selection remains challenging, neglecting neutral processes can lead to the incorrect identification of candidate loci. We here review the recent population genomic insights into the genetic basis of arsenic tolerance in Andean populations, and utilize this example to highlight both the difficulties pertaining to the identification of local adaptations in strongly bottlenecked populations, as well as the importance of controlling for demographic history in selection scans.
- Published
- 2019
28. Studying mutation rate evolution in primates—the effects of computational pipelines and parameter choices
- Author
-
Susanne P. Pfeifer
- Subjects
Mutation rate ,Phylogenetic tree ,Computer science ,AcademicSubjects/SCI02254 ,primates ,De novo mutation ,false-negative rate ,Health Informatics ,Computational biology ,Macaca mulatta ,de novo mutation ,Computer Science Applications ,computational pipeline ,Mutation Rate ,Mutation ,Commentary ,AcademicSubjects/SCI00960 ,Animals ,germline mutation rate ,Germ-Line Mutation ,Phylogeny ,false-positive rate - Abstract
This commentary investigates the important role of computational pipeline and parameter choices in performing mutation rate estimation, using the recent article published in this journal by Bergeron et al. entitled “The germline mutational process in rhesus macaque and its implications for phylogenetic dating” as an illustrative example.
- Published
- 2021
29. Mutationathon: towards standardization in estimates of pedigree-based germline mutation rates
- Author
-
Alivia Lee Price, Kelley Harris, Ellie E. Armstrong, Elora H. López-Nandam, Meritxell Riera, Jedidiah Carlson, Richard J. Wang, Lucie A. Bergeron, April S. Kleppe, George P. Tiley, Mikkel H. Schierup, Cyril J. Versoza, Tychele N. Turner, Hwei-yen Chen, Søren Besenbacher, Matthew W. Hahn, Guojie Zhang, Priya Moorjani, Susanne P. Pfeifer, and Anne D. Yoder
- Subjects
Mutation rate ,Germline mutation ,Future studies ,Standardization ,Statistics ,Pedigree chart ,Biology - Abstract
In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various non-human species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and how to appropriately account for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a “Mutationathon”, a competition organized among five research labs to compare germline mutation rate estimates for a single pedigree of rhesus macaques. We report almost a two-fold variation in the final estimated rate among groups using different post-alignment processing, calling, and filtering criteria and provide details into the sources of variation across studies. Though the difference among estimates is not statistically significant, this discrepancy emphasizes the need for standardized methods in mutation rate estimations and the difficulty in comparing rates from different studies. Finally, this work aims to provide guidelines for computational and statistical benchmarks for future studies interested in identifying germline mutations from pedigrees.
- Published
- 2021
30. Phylogenetic relationships and codon usage bias amongst cluster K mycobacteriophages
- Author
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Rohan Kapoor, Jueliet Menolascino, Adele Crane, Cyril J. Versoza, Rithik Mehta, Saige Munig, Daniel Sackett, Tiana Hua, Makena Sy, Lillian Lloyd, Zeel Patel, Abraham Morais, Brandon Schmit, and Susanne P. Pfeifer
- Subjects
AcademicSubjects/SCI01140 ,genome annotation ,AcademicSubjects/SCI00010 ,Mycobacteriophage ,Mycobacterium smegmatis ,mycobacteriophages ,codon usage bias ,Genome, Viral ,QH426-470 ,de novo assembly ,Biology ,Mycobacterium abscessus ,AcademicSubjects/SCI01180 ,phylogeny ,cluster K ,Genome ,Mycobacterium tuberculosis ,Genetics ,Humans ,Codon Usage ,Molecular Biology ,Genetics (clinical) ,Mycobacteriophages ,biology.organism_classification ,Genome Report ,Codon usage bias ,AcademicSubjects/SCI00960 ,Mycobacterium - Abstract
Bacteriophages infecting pathogenic hosts play an important role in medical research, not only as potential treatments for antibiotic-resistant infections but also offering novel insights into pathogen genetics and evolution. A prominent example is cluster K mycobacteriophages infecting Mycobacterium tuberculosis, a causative agent of tuberculosis in humans. However, as handling M. tuberculosis as well as other pathogens in a laboratory remains challenging, alternative nonpathogenic relatives, such as Mycobacterium smegmatis, are frequently used as surrogates to discover therapeutically relevant bacteriophages in a safer environment. Consequently, the individual host ranges of the majority of cluster K mycobacteriophages identified to date remain poorly understood. Here, we characterized the complete genome of Stinson, a temperate subcluster K1 mycobacteriophage with a siphoviral morphology. A series of comparative genomic analyses revealed strong similarities with other cluster K mycobacteriophages, including the conservation of an immunity repressor gene and a toxin/antitoxin gene pair. Patterns of codon usage bias across the cluster offered important insights into putative host ranges in nature, highlighting that although all cluster K mycobacteriophages are able to infect M. tuberculosis, they are less likely to have shared an evolutionary infection history with Mycobacterium leprae (underlying leprosy) compared to the rest of the genus’ host species. Moreover, subcluster K1 mycobacteriophages are able to integrate into the genomes of Mycobacterium abscessus and Mycobacterium marinum—two bacteria causing pulmonary and cutaneous infections which are often difficult to treat due to their drug resistance.
- Published
- 2021
31. The recombination landscapes of spiny lizards (genus Sceloporus)
- Author
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Cyril J Versoza, Julio A Rivera, Erica Bree Rosenblum, Cuauhcihuatl Vital-García, Diana K Hews, and Susanne P Pfeifer
- Subjects
Recombination, Genetic ,Species Specificity ,Karyotype ,Genetics ,Animals ,Lizards ,Molecular Biology ,Genetics (clinical) ,Phylogeny - Abstract
Despite playing a critical role in evolutionary processes and outcomes, relatively little is known about rates of recombination in the vast majority of species, including squamate reptiles—the second largest order of extant vertebrates, many species of which serve as important model organisms in evolutionary and ecological studies. This paucity of data has resulted in limited resolution on questions related to the causes and consequences of rate variation between species and populations, the determinants of within-genome rate variation, as well as the general tempo of recombination rate evolution on this branch of the tree of life. In order to address these questions, it is thus necessary to begin broadening our phylogenetic sampling. We here provide the first fine-scale recombination maps for two species of spiny lizards, Sceloporus jarrovii and Sceloporus megalepidurus, which diverged at least 12 Mya. As might be expected from similarities in karyotype, population-scaled recombination landscapes are largely conserved on the broad-scale. At the same time, considerable variation exists at the fine-scale, highlighting the importance of incorporating species-specific recombination maps in future population genomic studies.
- Published
- 2021
32. Linking a mutation to survival in wild mice
- Author
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Charles C.Y. Xu, Ricardo Mallarino, Matthieu Foll, Hopi E. Hoekstra, Jeffrey D. Jensen, Susanne P. Pfeifer, Kazumasa Wakamatsu, Stefan Laurent, Rowan D. H. Barrett, and Jonathan S. Duke-Cohan
- Subjects
0106 biological sciences ,0301 basic medicine ,Coat ,Peromyscus ,Genotype ,Population ,Mice, Transgenic ,Locus (genetics) ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,Gene Frequency ,Animals ,Selection, Genetic ,Hair Color ,education ,Allele frequency ,Sequence Deletion ,Melanins ,Genetics ,education.field_of_study ,Multidisciplinary ,Natural selection ,biology ,Pigmentation ,Nebraska ,biology.organism_classification ,Phenotype ,Mice, Inbred C57BL ,030104 developmental biology ,Mutation ,Agouti Signaling Protein ,sense organs - Abstract
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.
- Published
- 2019
33. Common Polymorphisms in the Glycoproteins of Human Cytomegalovirus and Associated Strain-Specific Immunity
- Author
-
Jeffrey D. Jensen, Hsuan Yuan Wang, Timothy F. Kowalik, Susanne P. Pfeifer, Sarah M. Valencia, and Sallie R. Permar
- Subjects
0301 basic medicine ,Human cytomegalovirus ,glycoprotein ,Cellular immunity ,viruses ,genotype ,030106 microbiology ,Cytomegalovirus ,Review ,Biology ,Antibodies, Viral ,Microbiology ,Genome ,polymorphism ,03 medical and health sciences ,Viral Envelope Proteins ,Immunity ,Virology ,Genetic variation ,Genotype ,medicine ,strain-specific immunity ,Humans ,chemistry.chemical_classification ,Immunity, Cellular ,Polymorphism, Genetic ,Strain (biology) ,medicine.disease ,Antibodies, Neutralizing ,QR1-502 ,030104 developmental biology ,Infectious Diseases ,chemistry ,human cytomegalovirus ,Immunology ,Cytomegalovirus Infections ,Glycoprotein - Abstract
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.
- Published
- 2021
34. Complete Genome Sequence of
- Author
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Mark, Milhaven, Erin, Hastings, Danielle, Brister, Leo, Cevallos, Sriya, Chilukuri, Arshia, Diyya, Aman, Garg, Rosaura, Hernandez, Daniel, Kelly, Karina, Lazo, Jennifer, Le, Garett, Maag, Palak D, Marfatia, Rithik, Mehta, Aram, Nejad, Jade, Porche, Alexander, Queiroz, Daniel, Sackett, Pablo, Santos Molina, Taylor, Slade, Minerva, So, Karan, Thakur, Angelica, Urquidez Negrete, Sage, Wackett, Sarah, Weiss, Liam, McCarthy, Keith, Wheaton, Adam D, Rudner, John P, McCutcheon, and Susanne P, Pfeifer
- Subjects
Genome Sequences - Abstract
We characterized the complete genome sequence of Siphoviridae bacteriophage Erla, an obligatory lytic subcluster EA1 bacteriophage infecting Microbacterium foliorum NRRL B-24224, with a capsid width of 65 nm and a tail length of 112 nm. The 41.5-kb genome, encompassing 62 predicted protein-coding genes, is highly similar (99.52% identity) to that of bacteriophage Calix.
- Published
- 2021
35. Complete Genome Sequence of Microbacterium Bacteriophage Erla
- Author
-
Daniel Kelly, Liam McCarthy, Taylor Slade, Karan Thakur, Palak D. Marfatia, Alexander Queiroz, Minerva So, Sage Wackett, Arshia Diyya, Jade Porche, Angelica Urquidez Negrete, Leo Cevallos, Adam D. Rudner, Sriya Chilukuri, Keith Wheaton, Pablo Santos Molina, Rosaura Hernandez, Aram Nejad, Aman Garg, Danielle Brister, Mark Milhaven, Karina Lazo, Susanne P. Pfeifer, Daniel Sackett, Sarah Weiss, Rithik Mehta, John P. McCutcheon, Erin Hastings, Garett Maag, and Jennifer Le
- Subjects
Whole genome sequencing ,Genetics ,0303 health sciences ,biology ,030306 microbiology ,Microbacterium ,biology.organism_classification ,medicine.disease_cause ,Genome ,Bacteriophage ,Siphoviridae ,03 medical and health sciences ,Immunology and Microbiology (miscellaneous) ,Lytic cycle ,Microbacterium foliorum ,medicine ,Molecular Biology ,Gene ,030304 developmental biology - Abstract
We characterized the complete genome sequence of Siphoviridae bacteriophage Erla, an obligatory lytic subcluster EA1 bacteriophage infecting Microbacterium foliorum NRRL B-24224, with a capsid width of 65 nm and a tail length of 112 nm. The 41.5-kb genome, encompassing 62 predicted protein-coding genes, is highly similar (99.52% identity) to that of bacteriophage Calix.
- Published
- 2021
36. The population genetics of crypsis in vertebrates: recent insights from mice, hares, and lizards
- Author
-
Stefan Laurent, Matthew R. Jones, Kristen K. Irwin, Michael W. Nachman, Jeffrey M. Good, Jeffrey D. Jensen, Susanne P. Pfeifer, Rebecca Harris, Rowan D. H. Barrett, and Catherine R. Linnen
- Subjects
sweeps ,Gene Flow ,0106 biological sciences ,0301 basic medicine ,Candidate gene ,mathematical-theory ,Population ,adaptive melanism ,Population genetics ,Inference ,Review Article ,Biology ,coloration ,010603 evolutionary biology ,01 natural sciences ,Evolutionary genetics ,phenotypic convergence ,03 medical and health sciences ,Peromyscus ,Genetics ,Animals ,Selection, Genetic ,education ,Genetics (clinical) ,Organism ,Selection (genetic algorithm) ,education.field_of_study ,Pigmentation ,Lizards ,Rare variants ,white ,Hares ,Adaptation, Physiological ,Biological Evolution ,Genetics, Population ,Phenotype ,030104 developmental biology ,Evolutionary biology ,Crypsis ,Adaptation ,evolutionary history ,local adaptation ,natural-selection - Abstract
By combining well-established population genetic theory with high-throughput sequencing data from natural populations, major strides have recently been made in understanding how, why, and when vertebrate populations evolve crypsis. Here, we focus on background matching, a particular facet of crypsis that involves the ability of an organism to conceal itself through matching its color to the surrounding environment. While interesting in and of itself, the study of this phenotype has also provided fruitful population genetic insights into the interplay of strong positive selection with other evolutionary processes. Specifically, and predicated upon the findings of previous candidate gene association studies, a primary focus of this recent literature involves the realization that the inference of selection from DNA sequence data first requires a robust model of population demography in order to identify genomic regions which do not conform to neutral expectations. Moreover, these demographic estimates provide crucial information about the origin and timing of the onset of selective pressures associated with, for example, the colonization of a novel environment. Furthermore, such inference has revealed crypsis to be a particularly useful phenotype for investigating the interplay of migration and selection-with examples of gene flow constraining rates of adaptation, or alternatively providing the genetic variants that may ultimately sweep through the population. Here, we evaluate the underlying evidence, review the strengths and weaknesses of the many population genetic methodologies used in these studies, and discuss how these insights have aided our general understanding of the evolutionary process.
- Published
- 2020
37. Spontaneous Mutation Rates
- Author
-
Susanne P. Pfeifer
- Subjects
Mutation rate ,Phylogenetic tree ,Human evolution ,Evolutionary biology ,Inference ,Pedigree chart ,Mutation–selection balance ,Biology ,Mutation Accumulation ,Neutral theory of molecular evolution - Abstract
There is a long-standing interest in the study of mutations—from the quest to enhance evolutionary inference related to the genetic underpinnings of disease, to the improvement of our understanding of the chronology of human evolution, to characterizing relationships between species. There is substantial uncertainty in historical estimates obtained from indirect methods: classical genetic approaches, going back to Haldane’s work in 1935 that utilized information from incidence of genetic disorders; and phylogenetic approaches, based on Kimura’s observation that under neutrality the mutation rate is equal to the rate of divergence. However, recent advances in high-throughput sequencing have made it possible to estimate mutation rates directly from parent-offspring trios and multigenerational pedigrees. Moreover, the combination of mutation accumulation studies with high-throughput sequencing has led to nearly complete, largely unbiased insights into the genome-wide spontaneous mutation rate in several experimentally tractable organisms. This chapter will focus on the basic concepts underlying the different methods used to estimate spontaneous mutation rates and will summarize current knowledge regarding the evolution of mutation rates across taxa.
- Published
- 2020
38. Germ Line Mutation Rates in Old World Monkeys
- Author
-
Lucy A. P. Tran and Susanne P. Pfeifer
- Subjects
0301 basic medicine ,Genetics ,03 medical and health sciences ,Mutation rate ,030104 developmental biology ,0302 clinical medicine ,Germline mutation ,Old World ,Mutation (genetic algorithm) ,Biology ,030217 neurology & neurosurgery ,Germline - Published
- 2018
39. The Demographic History of African Drosophila melanogaster
- Author
-
Stefan Laurent, Adamandia Kapopoulou, Jeffrey D. Jensen, and Susanne P. Pfeifer
- Subjects
0301 basic medicine ,Letter ,Range (biology) ,Demographic history ,Climate Change ,Population ,03 medical and health sciences ,inversion polymorphisms ,Genetics ,Animals ,Humans ,Colonization ,Selection, Genetic ,education ,Ecology, Evolution, Behavior and Systematics ,Demography ,Local adaptation ,education.field_of_study ,biology ,Human migration ,business.industry ,Null model ,demographic inference ,biology.organism_classification ,Drosophila melanogaster ,Genetics, Population ,030104 developmental biology ,Evolutionary biology ,Africa ,business - Abstract
As one of the most commonly utilized organisms in the study of local adaptation, an accurate characterization of the demographic history of Drosophila melanogaster remains as an important research question. This owes both to the inherent interest in characterizing the population history of this model organism, as well as to the well-established importance of an accurate null demographic model for increasing power and decreasing false positive rates in genomic scans for positive selection. Although considerable attention has been afforded to this issue in non-African populations, less is known about the demographic history of African populations, including from the ancestral range of the species. While qualitative predictions and hypotheses have previously been forwarded, we here present a quantitative model fitting of the population history characterizing both the ancestral Zambian population range as well as the subsequently colonized west African populations, which themselves served as the source of multiple non-African colonization events. We here report the split time of the West African population at 72 kya, a date corresponding to human migration into this region as well as a period of climatic changes in the African continent. Furthermore, we have estimated population sizes at this split time. These parameter estimates thus represent an important null model for future investigations in to African and non-African D. melanogaster populations alike.
- Published
- 2018
40. A genetic reconstruction of the invasion of the calanoid copepod Pseudodiaptomus inopinus across the North American Pacific Coast
- Author
-
Ho Young Soh, Jeffery R. Cordell, Gretchen Rollwagen-Bollens, Séverine Vuilleumier, Stephen M. Bollens, Eric Dexter, Susanne P. Pfeifer, and Jérôme Goudet
- Subjects
0106 biological sciences ,0301 basic medicine ,Ecology ,biology ,Range (biology) ,Aquatic ecosystem ,Pseudodiaptomus inopinus ,Plankton ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,Crustacean ,Zooplankton ,03 medical and health sciences ,030104 developmental biology ,14. Life underwater ,Ecology, Evolution, Behavior and Systematics ,Genetic composition ,Copepod - Abstract
The rate of aquatic invasions by planktonic organisms has increased considerably in recent decades. In order to effectively direct funding and resources to control the spread of such invasions, a methodological framework for identifying high-risk transport vectors, as well as ruling out vectors of lesser concern will be necessary. A number of estuarine ecosystems on the North American Pacific Northwest coast have experienced a series of high impact planktonic invasions that have slowly unfolded across the region in recent decades, most notably, that of the planktonic copepod crustacean Pseudodiaptomus inopinus. Although introduction of P. inopinus to the United States almost certainly occurred through the discharge of ballast water from commercial vessels originating in Asia (the species’ native range), the mechanisms and patterns of subsequent spread remain unknown. In order to elucidate the migration events shaping this invasion, we sampled the genomes of copepods from seven invasive and two native populations using restriction-site associated DNA sequencing. This genetic data was evaluated against spatially-explicit genetic simulation models to evaluate competing scenarios of invasion spread. Our results indicate that invasive populations of P. inopinus exhibit a geographically unstructured genetic composition, likely arising from infrequent and large migration events. This pattern of genetic patchiness was unexpected given the linear geographic structure of the sampled populations, and strongly contrasts with the clear invasion corridors observed in many aquatic systems.
- Published
- 2017
41. Direct estimate of the spontaneous germ line mutation rate in African green monkeys
- Author
-
Susanne P. Pfeifer
- Subjects
0301 basic medicine ,Genetics ,Mutation rate ,biology ,Point mutation ,Population genetics ,Old World monkey ,biology.organism_classification ,03 medical and health sciences ,030104 developmental biology ,Germline mutation ,Effective population size ,African Green Monkey ,Vervet monkey ,General Agricultural and Biological Sciences ,Ecology, Evolution, Behavior and Systematics - Abstract
Here, I provide the first direct estimate of the spontaneous mutation rate in an Old World monkey, using a seven individual, three-generation pedigree of African green monkeys. Eight de novo mutations were identified within ∼1.5 Gbp of accessible genome, corresponding to an estimated point mutation rate of 0.94 × 10-8 per site per generation, suggesting an effective population size of ∼12000 for the species. This estimation represents a significant improvement in our knowledge of the population genetics of the African green monkey, one of the most important nonhuman primate models in biomedical research. Furthermore, by comparing mutation rates in Old World monkeys with the only other direct estimates in primates to date-humans and chimpanzees-it is possible to uniquely address how mutation rates have evolved over longer time scales. While the estimated spontaneous mutation rate for African green monkeys is slightly lower than the rate of 1.2 × 10-8 per base pair per generation reported in chimpanzees, it is similar to the lower range of rates of 0.96 × 10-8 -1.28 × 10-8 per base pair per generation recently estimated from whole genome pedigrees in humans. This result suggests a long-term constraint on mutation rate that is quite different from similar evidence pertaining to recombination rate evolution in primates.
- Published
- 2017
42. The ultimate and proximate mechanisms driving the evolution of long tails in forest deer mice
- Author
-
Krzysztof M. Kozak, Susanne P. Pfeifer, Dou-Shuan Yang, Hopi E. Hoekstra, and Evan P. Kingsley
- Subjects
0301 basic medicine ,education.field_of_study ,Peromyscus ,biology ,Range (biology) ,Ecology ,Population ,biology.organism_classification ,03 medical and health sciences ,Phylogeography ,030104 developmental biology ,Evolutionary biology ,Convergent evolution ,Genetics ,medicine ,Deer mouse ,medicine.vector_of_disease ,Parallel evolution ,General Agricultural and Biological Sciences ,education ,Ecology, Evolution, Behavior and Systematics ,Local adaptation - Abstract
Understanding both the role of selection in driving phenotypic change and its underlying genetic basis remain major challenges in evolutionary biology. Here, we use modern tools to revisit a classic system of local adaptation in the North American deer mouse, Peromyscus maniculatus, which occupies two main habitat types: prairie and forest. Using historical collections, we find that forest-dwelling mice have longer tails than those from nonforested habitat, even when we account for individual and population relatedness. Using genome-wide SNP data, we show that mice from forested habitats in the eastern and western parts of their range form separate clades, suggesting that increased tail length evolved independently. We find that forest mice in the east and west have both more and longer caudal vertebrae, but not trunk vertebrae, than nearby prairie forms. By intercrossing prairie and forest mice, we show that the number and length of caudal vertebrae are not correlated in this recombinant population, indicating that variation in these traits is controlled by separate genetic loci. Together, these results demonstrate convergent evolution of the long-tailed forest phenotype through two distinct genetic mechanisms, affecting number and length of vertebrae, and suggest that these morphological changeseither independently or togetherare adaptive.
- Published
- 2016
43. The Evolutionary History of Nebraska Deer Mice: Local Adaptation in the Face of Strong Gene Flow
- Author
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Jeffrey D. Jensen, Laurent Excoffier, Susanne P. Pfeifer, Matthieu Foll, Vitor C. Sousa, Hopi E. Hoekstra, Catherine R. Linnen, and Stefan Laurent
- Subjects
Genetics ,0301 basic medicine ,Haplotype ,Selection coefficient ,population genetics ,Population genetics ,Single-nucleotide polymorphism ,Locus (genetics) ,adaptation ,Biology ,cryptic coloration ,Gene flow ,03 medical and health sciences ,030104 developmental biology ,Genetic drift ,Evolutionary biology ,Fast Track ,570 Life sciences ,biology ,Allele ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Local adaptation - Abstract
The interplay of gene flow, genetic drift, and local selective pressure is a dynamic process that has been well studied from a theoretical perspective over the last century. Wright and Haldane laid the foundation for expectations under an island-continent model, demonstrating that an island specific beneficial allele may be maintained locally if the selection coefficient is larger than the rate of migration of the ancestral allele from the continent. Subsequent extensions of this model have provided considerably more insight into the conditions under which such a beneficial allele may be maintained, lost, or fixed. Yet, connecting theoretical results with empirical data has proven challenging, owing to a lack of information on the relationship between genotype, phenotype, and fitness. Here, we examine the demographic and selective history of deer mice in and around the Nebraska Sand Hills, a system in which variation at the Agouti locus affects cryptic coloration that in turn affects the survival of mice in their local habitat. We first genotyped 250 individuals from eleven sites along a transect spanning the Sand Hills at 670,000 SNPs across the genome. Using these genomic data, we found that deer mice first colonized the Sand Hills following the last glacial period. Subsequent high rates of gene flow have served to homogenize the majority of the genome between populations on and off the Sand Hills, with the exception of the Agouti pigmentation locus. Furthermore, we observe strong haplotype structure around putatively beneficial mutations within the Agouti locus, and these mutations are strongly associated with the pigment traits that are strongly correlated with local soil coloration and thus responsible for cryptic coloration. We discuss these empirical results in light of theoretical expectations, thereby providing a complete example of the dynamics between ancestral gene flow and local adaptation in a classic mammalian system.
- Published
- 2018
- Full Text
- View/download PDF
44. On the Analysis of Intrahost and Interhost Viral Populations: Human Cytomegalovirus as a Case Study of Pitfalls and Expectations
- Author
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Timothy F. Kowalik, Nicholas Renzette, Jeffrey D. Jensen, Susanne P. Pfeifer, and Sebastian Matuszewski
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0106 biological sciences ,0301 basic medicine ,Human cytomegalovirus ,Genes, Viral ,Population level ,intrahost diversity ,Immunology ,Cytomegalovirus ,Population genetics ,Biology ,010603 evolutionary biology ,01 natural sciences ,Microbiology ,Nucleotide diversity ,Evolution, Molecular ,03 medical and health sciences ,Gene Frequency ,Virology ,Genetic model ,medicine ,Humans ,Alleles ,Phylogeny ,Genetics ,Polymorphism, Genetic ,Models, Genetic ,population genetics ,interhost diversity ,medicine.disease ,030104 developmental biology ,Genetic Diversity and Evolution ,human cytomegalovirus ,Insect Science ,Cytomegalovirus Infections ,Genetic Fitness ,Fitness effects - Abstract
Intrahost and interhost assessments of viral diversity are often treated as measures of separate and distinct evolutionary processes, with numerous investigations reporting seemingly incompatible results between the two. For example, in human cytomegalovirus, the nucleotide diversity estimates are 10-fold higher for interhost data, while the number of segregating (i.e., polymorphic) sites is 6-fold lower. These results have been interpreted as demonstrating that sampled intrahost variants are strongly deleterious. In reality, however, these observations are fully consistent with standard population genetic expectations. Here, we analyze published intra- and interhost data sets within this framework, utilizing statistical inference tools to quantify the fitness effects of segregating mutations. Further, we utilize population level simulations to clarify expectations under common evolutionary models. Contrary to common claims in the literature, these results suggest that most observed polymorphisms are likely nearly neutral with regard to fitness and that standard population genetic models in fact well predict observed levels of both intra- and interhost variability. IMPORTANCE With the increasing number of evolutionary virology studies examining both intrahost and interhost patterns of genomic variation, a number of seemingly incompatible results have emerged, revolving around the far greater level of observed intrahost than interhost variation. This has led many authors to suggest that the great majority of sampled within-host polymorphisms are strongly deleterious. Here, we demonstrate that there is in fact no incompatibility of these results and, indeed, that the vast majority of sampled within-host variation is likely neutral. These results thus represent a major shift in the current view of observed viral variation.
- Published
- 2017
45. The Demographic and Adaptive History of the African Green Monkey
- Author
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Susanne P. Pfeifer
- Subjects
0301 basic medicine ,Population fragmentation ,Mutation rate ,Demographic history ,Adaptation, Biological ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Chlorocebus aethiops ,Genetics ,Animals ,Vervet monkey ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,Demography ,Genetic diversity ,Genome ,biology ,Genetic Variation ,biology.organism_classification ,Biological Evolution ,030104 developmental biology ,Evolutionary biology ,African Green Monkey ,Adaptation - Abstract
Relatively little is known about the evolutionary history of the African green monkey (genus Chlorocebus) due to the lack of sampled polymorphism data from wild populations. Yet, this characterization of genetic diversity is not only critical for a better understanding of their own history, but also for human biomedical research given that they are one of the most widely used primate models. Here, I analyze the demographic and selective history of the African green monkey, utilizing one of the most comprehensive catalogs of wild genetic diversity to date, consisting of 1,795,643 autosomal single nucleotide polymorphisms in 25 individuals, representing all five major populations: C. a. aethiops, C. a. cynosurus, C. a. pygerythrus, C. a. sabaeus, and C. a tantalus. Assuming a mutation rate of 5.9 × 10-9 per base pair per generation and a generation time of 8.5 years, divergence time estimates range from 523 to 621 kya for the basal split of C. a. aethiops from the other four populations. Importantly, the resulting tree characterizing the relationship and split-times between these populations differs significantly from that presented in the original genome paper, owing to their neglect of within-population variation when calculating between population-divergence. In addition, I find that the demographic history of all five populations is well explained by a model of population fragmentation and isolation, rather than novel colonization events. Finally, utilizing these demographic models as a null, I investigate the selective history of the populations, identifying candidate regions potentially related to adaptation in response to pathogen exposure.
- Published
- 2017
46. Characterizing human cytomegalovirus reinfection in congenitally infected infants: an evolutionary perspective
- Author
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Marisa Márcia Mussi-Pinhata, Aparecida Yulie Yamamoto, Laura Gibson, Nicholas Renzette, Kristen K. Irwin, William J. Britt, Cornelia Pokalyuk, Jeffrey D. Jensen, Susanne P. Pfeifer, and Timothy F. Kowalik
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0301 basic medicine ,Human cytomegalovirus ,Population ,Cytomegalovirus ,Context (language use) ,Biology ,Virus ,Evolution, Molecular ,03 medical and health sciences ,Pregnancy ,Molecular evolution ,GRAVIDEZ ,Genetics ,medicine ,Humans ,education ,Ecology, Evolution, Behavior and Systematics ,education.field_of_study ,Models, Genetic ,Transmission (medicine) ,Infant, Newborn ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Infant ,Evolutionary medicine ,Sequence Analysis, DNA ,medicine.disease ,Genetics, Population ,030104 developmental biology ,Cytomegalovirus Infections ,DNA, Viral ,Immunology ,Female - Abstract
Given the strong selective pressures often faced by populations when colonizing a novel habitat, the level of variation present on which selection may act is an important indicator of adaptive potential. While often discussed in an ecological context, this notion is also highly relevant in our clinical understanding of viral infection, in which the novel habitat is a new host. Thus, quantifying the factors determining levels of variation is of considerable importance for the design of improved treatment strategies. Here, we focus on such a quantification of human cytomegalovirus (HCMV) - a virus which can be transmitted across the placenta, resulting in foetal infection that can potentially cause severe disease in multiple organs. Recent studies using genomewide sequencing data have demonstrated that viral populations in some congenitally infected infants diverge rapidly over time and between tissue compartments within individuals, while in other infants, the populations remain highly stable. Here, we investigate the underlying causes of these extreme differences in observed intrahost levels of variation by estimating the underlying demographic histories of infection. Importantly, reinfection (i.e. population admixture) appears to be an important, and previously unappreciated, player. We highlight illustrative examples likely to represent a single-population transmission from a mother during pregnancy and multiple-population transmissions during pregnancy and after birth.
- Published
- 2017
47. A fine-scale chimpanzee genetic map from population sequencing
- Author
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Zamin Iqbal, Oliver Venn, Peter Humburg, Adam Auton, John Broxholme, Gil McVean, Adi Fledel-Alon, Cord Melton, Simon Myers, Molly Przeworski, Julian Maller, Ryan D. Hernandez, Rory Bowden, Ivy Aneas, Ellen M. Leffler, Teresa L Street, Aarti Venkat, Marcelo A. Nobrega, Gerton Lunter, Susanne P. Pfeifer, Laure Ségurel, Ronald E. Bontrop, Peter Donnelly, Max Planck Institute for Meteorology (MPI-M), Max-Planck-Gesellschaft, University of Chicago, University of Agriculture Faisalabad (UAF), Department of Comparative Genetics and Refinement [Rijswijk, The Netherlands], and Biomedical Primate Research Centre [Rijswijk] (BPRC)
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Male ,Pan troglodytes ,Population ,Biology ,Polymorphism, Single Nucleotide ,Evolution, Molecular ,03 medical and health sciences ,0302 clinical medicine ,Species Specificity ,Genetic variation ,Animals ,Humans ,education ,Gene ,ComputingMilieux_MISCELLANEOUS ,PRDM9 ,030304 developmental biology ,Recombination, Genetic ,Genetics ,0303 health sciences ,education.field_of_study ,[SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE] ,Multidisciplinary ,Base Sequence ,Haplotype ,Chromosome Mapping ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Chromosome ,Histone-Lysine N-Methyltransferase ,Sequence Analysis, DNA ,Chromosomes, Mammalian ,Haplotypes ,CpG site ,Chromosomes, Human, Pair 2 ,CpG Islands ,Female ,030217 neurology & neurosurgery ,Recombination - Abstract
Going Ape Over Genetic Maps Recombination is an important process in generating diversity and producing selectively advantageous genetic combinations. Thus, changes in recombination hotspots may influence speciation. To investigate the variation in recombination processes in humans and their closest existing relatives, Auton et al. (p. 193 , published online 15 March) prepared a fine-scale genetic map of the Western chimpanzee and compared it with that of humans. While rates of recombination are comparable between humans and chimpanzees, the locations and genetic motifs associated with recombination differ between the species.
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- 2016
48. From next-generation resequencing reads to a high-quality variant data set
- Author
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Susanne P. Pfeifer
- Subjects
0301 basic medicine ,Quality Control ,media_common.quotation_subject ,Genomics ,Variation (game tree) ,Review ,Biology ,computer.software_genre ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Data accuracy ,Human population genetics ,Genetics ,Quality (business) ,Genetics (clinical) ,media_common ,High-Throughput Nucleotide Sequencing ,Sequence Analysis, DNA ,Post genomics ,Data Accuracy ,Data set ,030104 developmental biology ,Data mining ,computer ,Sequence Alignment ,030217 neurology & neurosurgery - Abstract
Sequencing has revolutionized biology by permitting the analysis of genomic variation at an unprecedented resolution. High-throughput sequencing is fast and inexpensive, making it accessible for a wide range of research topics. However, the produced data contain subtle but complex types of errors, biases and uncertainties that impose several statistical and computational challenges to the reliable detection of variants. To tap the full potential of high-throughput sequencing, a thorough understanding of the data produced as well as the available methodologies is required. Here, I review several commonly used methods for generating and processing next-generation resequencing data, discuss the influence of errors and biases together with their resulting implications for downstream analyses and provide general guidelines and recommendations for producing high-quality single-nucleotide polymorphism data sets from raw reads by highlighting several sophisticated reference-based methods representing the current state of the art.
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- 2016
49. Multiple genetic changes underlie the evolution of long-tailed forest deer mice
- Author
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Susanne P. Pfeifer, Evan P. Kingsley, Dou-Shuan Yang, Hopi E. Hoekstra, and Krzysztof M. Kozak
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0106 biological sciences ,0303 health sciences ,education.field_of_study ,Peromyscus ,Ecology ,Range (biology) ,Population ,Biology ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,Habitat ,Evolutionary biology ,Convergent evolution ,medicine ,Deer mouse ,medicine.vector_of_disease ,Clade ,education ,030304 developmental biology ,Local adaptation - Abstract
Understanding both the role of selection in driving phenotypic change and its underlying genetic basis remain major challenges in evolutionary biology. Here we focus on a classic system of local adaptation in the North American deer mouse,Peromyscus maniculatus, which occupies two main habitat types, prairie and forest. Using historical collections we demonstrate that forest-dwelling mice have longer tails than those from non-forested habitats, even when we account for individual and population relatedness. Based on genome-wide SNP capture data, we find that mice from forested habitats in the eastern and western parts of their range form separate clades, suggesting that increased tail length evolved independently from a short-tailed ancestor. Two major changes in skeletal morphology can give rise to longer tails--increased number and increased length of vertebrae--and we find that forest mice in the east and west have both more and longer caudal vertebrae, but not trunk vertebrae, than nearby prairie forms. Using a second-generation intercross between a prairie and forest pair, we show that the number and length of caudal vertebrae are not correlated in this recombinant population, suggesting that variation in these traits is controlled by separate genetic loci. Together, these results demonstrate convergent evolution of the long-tailed forest phenotype through multiple, distinct genetic mechanisms (controlling vertebral length and vertebral number), thus suggesting that these morphological changes--either independently or together--are adaptive.
- Published
- 2016
50. On the Demographic and Selective Forces Shaping Patterns of Human Cytomegalovirus Variation within Hosts
- Author
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Jeffrey D. Jensen, Susanne P. Pfeifer, Timothy F. Kowalik, and Andrew M. Sackman
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0301 basic medicine ,Microbiology (medical) ,Human cytomegalovirus ,viruses ,lcsh:Medicine ,Review ,Biology ,medicine.disease_cause ,Herpesviridae ,viral evolution ,03 medical and health sciences ,medicine ,Immunology and Allergy ,Molecular Biology ,General Immunology and Microbiology ,lcsh:R ,population genetics ,virus diseases ,Transplacental ,medicine.disease ,Virology ,3. Good health ,030104 developmental biology ,Infectious Diseases ,Mild symptoms ,human cytomegalovirus ,Viral evolution - Abstract
Human cytomegalovirus (HCMV) is a member of the β -herpesvirus subfamily within Herpesviridae that is nearly ubiquitous in human populations, and infection generally results only in mild symptoms. However, symptoms can be severe in immunonaive individuals, and transplacental congenital infection of HCMV can result in serious neurological sequelae. Recent work has revealed much about the demographic and selective forces shaping the evolution of congenitally transmitted HCMV both on the level of hosts and within host compartments, providing insight into the dynamics of congenital infection, reinfection, and evolution of HCMV with important implications for the development of effective treatments and vaccines.
- Published
- 2018
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