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I study foundational questions in evolutionary theory, by building toy models to incorporate mechanistic phenomena within population genetic models, and by applying model insights to bioinformatic data. Two of my central research interests are i) the robustness and evolvability of biological systems, and ii) how best to describe fitness in a density-dependent and frequency-dependent world. Specific systems include prions, evolutionary capacitance, the evolution of error rates, and the birth of protein-coding sequences from non-coding DNA. I am especially interested in the error-prone nature of molecular (eg transcription, translation, folding) and other developmental processes. Errors in the present can mimic future mutations, and so when selection against the consequences of present errors is strong, this changes the distribution of possible mutations in ways that can have profound consequences. I am also interested in the tension between relative and absolute contests.Show Less
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Courses
- IMBIntroduction to Modeling in Biology
- EMEvidence-based Medicine
- REEResearch in Ecology and Evolution
Grants
- What Life Wants: Exploring the Natural Selection of Elements
Principal Investigator (PI)
2022
$63.4K
Active - Universal Principles of Evolutionary Adaptation
Principal Investigator (PI)
2021
$249.4K
Active - Does an Evolutionary Ratchet of Complexity Rescue Us from Mutation Load?
Principal Investigator (PI)
2020
$564.3K
Active - HHMI Professor Masel 2017
Principal Investigator (PI)
2018
$20.0K
- A Long-Term Arrow of Protein Evolutionary Time
Principal Investigator (PI)
2017
$642.0K
- Ecological effects of clonal interference in a changing environment.
Principal Investigator (PI)
2014
$249.6K
- The Conversion of Noncoding Sequences Into Proteins
Co-Investigator (COI)
2013
$835.3K
- Evolvability, preadaption, and the evolution of something from nothing
Principal Investigator (PI)
2013
$471.9K
- Chance, Purpose and Progress in Evolution and Christianity: A Forum at the University of Arizona
Principal Investigator (PI)
2010
$34.5K
- Pew Scholars Program: Evolution and Robutness of Transcriptional Networks
Principal Investigator (PI)
2007
$240.0K
Technologies / Patents
News
- How a Smartphone App and Contact Tracing Helped Keep UArizona Open and Curb COVID-19 Spread
2020
- UArizona and Covid Watch Launch COVID-19 Exposure Notification App
2020
- A Chicken-Egg Question: Where Do Baby Genes Come From?
2017
- Birth of a New Protein: How Evolution Does More Than Tinker
2017
- Fountain of Youth? Sorry, It's Not Out There
2017
- UA Biologists Awarded John Templeton Foundation Grants for Research on Genetics, Diversity of Life
2013
- Study: Texting Increases Turnout to Campus Blood Drive
2012
- Evolution by Mistake
2011
- Undergraduate Biology Research Program Earns $1.8M Grant
2010
- Biosphere 2 Short Course is First Class, Arizona Science, Math Teachers Say
2009
- Charles Darwin is Topic for Spring 2009 St. Albert the Great Forum
2009
- Prestigious Pew Award Goes to the UA’s Felicia Goodrum
2008
- Science Center Cafe will Address Science and Religion
2007
- Flandrau to Hold Informal Science Chat
2007
Publications (94)
Recent
- Differential retention of Pfam domains contributes to long-term evolutionary trends
2023
- The effectiveness of selection in a species affects the direction of amino acid frequency evolution
2023
- A new codon adaptation metric predicts vertebrate body size and tendency to protein disorder
2023
- Unlinked background selection reduces neutral diversity more than linked background selection
2022
- Background selection theory overestimates effective population size for high mutation rates
2022
- nQMaker: Estimating Time Nonreversible Amino Acid Substitution Models
2022
- Quantifying SARS‐CoV‐2 infection risk within the Google/Apple Exposure Notification framework to inform quarantine recommendations
2022
- Genetics of adaptation and fitness landscapes: From toy models to testable quantitative predictions
2022
- Differential retention of Pfam domains creates long-term evolutionary trends
2022
- Improving Ancestral Sequence Reconstruction Using Better Amino Acid Substitution Matrices
2022
- Selection on the amino acid frequencies of structurally disordered proteins
2022
- Misrepresenting biases in arrival: a comment on Svensson (2022)
2022
- The cost of selection in selective deaths paid out of reproductive excess
2021
- Quantifying meaningful usage of a SARS-CoV-2 exposure notification app on the campus of the University of Arizona
2021
- Haldane’s cost of selection imposes a mild constraint on adaptation, with a high proportion of deaths in A. thaliana being selective
2021
- Modelling the effectiveness and social costs of daily lateral flow antigen tests versus quarantine in preventing onward transmission of COVID-19 from traced contacts
2021
- The economic value of quarantine is higher at lower case prevalence, with quarantine justified at lower risk of infection
2020
- Random peptides rich in small and disorder-promoting amino acids are less likely to be harmful
2020
- Quantifying SARS-CoV-2 infection risk within the Apple/Google exposure notification framework to inform quarantine recommendations
2020
- Only a Single Taxonomically Restricted Gene Family in the Drosophila melanogaster Subgroup Can Be Identified with High Confidence
2020
- The timing of COVID-19 transmission
2020
- The protein domains of vertebrate species in which selection is more effective have greater intrinsic structural disorder
2020
- Differences in evolutionary accessibility determine which equally effective regulatory motif evolves to generate pulses
2020
- Mutational Analysis of SARS-CoV-2 Genome in African Population (preprint)
2020
- Universal and taxon-specific trends in protein sequences as a function of age
2020
- Mutation bias can shape adaptation in large asexual populations experiencing clonal interference
2020
- Density-dependent selection and the limits of relative fitness
2019
- High transcriptional error rates vary as a function of gene expression level
2019
- Different mechanisms drive the maintenance of polymorphism at loci subject to strong versus weak fluctuating selection
2019
- Evolution rapidly optimizes stability and aggregation in lattice proteins despite pervasive landscape valleys and mazes
2019
- Readthrough errors purge deleterious cryptic sequences, facilitating the birth of coding sequences
2019
- Biomarkers for aging identified in cross-sectional studies tend to be non-causative
2019
- Directional selection rather than functional constraints can shape the G matrix in rapidly adapting asexuals
2018
- Reply to Cheong et al.: Unicellular survival precludes Parrondo’s paradox
2018
- Gene Birth Contributes to Structural Disorder Encoded by Overlapping Genes
2018
- Evolutionary capacitance emerges spontaneously during adaptation to environmental changes
2018
- Reply to Mitteldorf and Fahy: Aging is still inevitable
2018
- Feed-forward regulation adaptively evolves via dynamics rather than topology when there is intrinsic noise
2018
- Drift Barriers to Quality Control When Genes Are Expressed at Different Levels
2017
- A shift in aggregation avoidance strategy marks a long-term direction to protein evolution
2017
- Intercellular competition and the inevitability of multicellular aging
2017
- Foldability of a natural de novo evolved protein
2017
- Young genes are highly disordered as predicted by the preadaptation hypothesis of de novo gene birth
2017
- Predicting patterns of long‐term adaptation and extinction with population genetics
2017
- Drift barriers for the proofreading of genes expressed at different levels
2016
- Answering evolutionary questions: A guide for mechanistic biologists
2016
- Outcome orientation: A misconception of probability that harms medical research and practice
2016
- Evidence-based medicine as a tool for undergraduate probability and statistics education
2015
- What Fraction of Duplicates Observed in Recently Sequenced Genomes Is Segregating and Destined to Fail to Fix?
2015
- Constraints on the evolution of phenotypic plasticity: limits and costs of phenotype and plasticity
2015
- The Recent De Novo Origin of Protein C-Termini
2015
- Drift barriers and evolvability
2015
- Eco-evolutionary" fitness" in 3 dimensions: absolute growth, absolute efficiency, and relative competitiveness
2014
- Cryptic genetic variation can make irreducible complexity a common mode of adaptation in sexual populations
2014
- CHANCE, PURPOSE, AND PROGRESS IN EVOLUTION AND CHRISTIANITY
2014
- Q A: Evolutionary capacitance
2013
- Q&A: evolutionary capacitance
2013
- Q&A: Evolutionary capacitance.
2013
- Compensatory evolution and the origins of innovations
2013
- Rethinking Hardy–Weinberg and genetic drift in undergraduate biology
2012
- Putatively Noncoding Transcripts Show Extensive Association with Ribosomes
2011
- Evolution of molecular error rates and the consequences for evolvability.
2011
- The spontaneous appearance rate of the yeast prion [PSI+] and its implications for the evolution of the evolvability properties of the [PSI+] system.
2010
- The Spontaneous Appearance Rate of the Yeast Prion [PSI+] and Its Implications for the Evolution of the Evolvability Properties of the [PSI+] System
2010
- The Effects of Selection Against Translational Errors on the Evolution of Protein Evolvability
2010
- Quantitative Prediction of Molecular Clock and Ka/Ks at Short Timescales
2009
- Complex adaptations can drive the evolution of the capacitor [PSI sup + /sup ], even with realistic rates of yeast sex
2009
- Quantitative prediction of molecular clock and ka/ks at short timescales.
2009
- The strength of selection against the yeast prion [PSI sup + /sup ]
2009
- Quantitative prediction of molecular clock and K sup a/K /sup s at short timescales
2009
- The Strength of Selection Against the Yeast Prion [PSI+]
2009
- The conversion of 3′ UTRs into coding regions
2007
- The Roles of Mutation Accumulation and Selection in Loss of Sporulation in Experimental Populations of Bacillus subtilis
2007
- The roles of mutation accumulation and selection in loss of sporulation in experimental populations of Bacillus subtilis.
2007
- The population genetics of phenotypic deterioration in experimental populations of Bacillus subtilis.
2006
- Transplantation of hNT neurons into the ischemic cortex: cell survival and effect on sensorimotor behavior
2006
- Mutations Leading to Loss of Sporulation Ability in Bacillus subtilis Are Sufficiently Frequent to Favor Genetic Canalization
2006
- Efficient inhibition of prion replication by PrP-Fc sub 2 /sub suggests that the prion is a PrP sup Sc /sup oligomer
2005
- Evolutionary Capacitance May Be Favored by Natural Selection
2005
- Cryptic Genetic Variation Is Enriched for Potential Adaptations
2005
- Prion Kinetics (multiple letters)
2004
- Genetic assimilation can occur in the absence of selection for the assimilating phenotype, suggesting a role for the canalization heuristic
2004
- Human CNS stem cell transplantation in rat stroke: Assessment of cell biology and functional recovery
2004
- Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex
2004
- The evolution of the evolvability properties of the yeast prion [PSI+].
2003
- The evolution of the evolvability properties of the yeast prion [PSI sup + /sup ]
2003
- The molecular biology of prion propagation-Discussion
2001
- The measured level of prion infectivity varies in a predictable way according to the aggregation state of the infectious agent
2001
- From genetics to pathology: tau and α-synuclein assemblies in neurodegenerative diseases-Discussion
2001
- The molecular biology of prion propagation
2001
- Prion protein interconversions-Discussion
2001
- The replication kinetics of prions and other amyloids.
2000
- The kinetics of proteinase K digestion of linear prion polymers
1999