A5081790648- Evolution and Genetic Dynamics
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Genetic diversity and population structure
- Evolutionary Game Theory and Cooperation
- Gene Regulatory Network Analysis
- Plant and animal studies
- Prion Diseases and Protein Misfolding
- Bacterial Genetics and Biotechnology
- Protein Structure and Dynamics
- COVID-19 epidemiological studies
- COVID-19 Digital Contact Tracing
- Animal Behavior and Reproduction
- Mathematical and Theoretical Epidemiology and Ecology Models
- CRISPR and Genetic Engineering
- Microbial Metabolic Engineering and Bioproduction
- Fungal and yeast genetics research
- Bioinformatics and Genomic Networks
- SARS-CoV-2 and COVID-19 Research
- RNA Research and Splicing
- SARS-CoV-2 detection and testing
- Machine Learning in Bioinformatics
- Genetic Mapping and Diversity in Plants and Animals
- Genetic Associations and Epidemiology
- Plant Virus Research Studies
University of Arizona
2016-2025
Stanford University
2003-2024
Uppsala University
2024
Uniformed Services University of the Health Sciences
2021
Madigan Army Medical Center
2021
Henry M. Jackson Foundation
2021
Health Solutions (Sweden)
2020
StemCells (United States)
2004
Centre for Human Genetics
1999-2001
University of Oxford
1999-2001
We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into ischemic cortex rats 7 days after distal middle cerebral artery occlusion. Transplanted survived robustly in naive brains 4 wk posttransplant. Survival was influenced by proximity graft to stroke lesion negatively correlated with number IB4-positive inflammatory cells. Targeted migration seen animals, many migrating long distances (≈1.2 mm) predominantly toward...
There have been recent surprising reports that whole genes can evolve de novo from noncoding sequences.This would be extraordinary if the sequences were random with respect to amino acid identity.However, previously translated at low rates, most strongly deleterious cryptic polypeptides purged by selection, then gene origination more plausible.Here we analyze Saccharomyces cerevisiae data on transcripts found in association ribosomes.We find many such transcripts.Although their average...
Abstract The timing of SARS-CoV-2 transmission is a critical factor to understand the epidemic trajectory and impact isolation, contact tracing other non-pharmaceutical interventions on spread COVID-19 epidemics. We examined distribution events with respect exposure onset symptoms. show that for symptomatic individuals, more strongly linked clinical symptoms than time since infection. found it was approximately centered symmetric around symptoms, three quarters occurring in window from 2-3...
Current theories attribute aging to a failure of selection, due either pleiotropic constraints or declining strength selection after the onset reproduction. These implicitly leave open possibility that if senescence-causing alleles could be identified, antagonistic pleiotropy broken, effects might ameliorated delayed indefinitely. are built on models between multicellular organisms, but full understanding also requires examining role somatic within an organism. Selection cells (i.e.,...
Cryptic genetic variation accumulates under weakened selection and has been proposed as a source of evolutionary innovations. Weakened may, however, also lead to the accumulation strongly deleterious or lethal alleles, swamping effect any potentially adaptive alleles when they are revealed. Here I model that is partially shielded from selection, assuming unconditionally more than in future environment. find cryptic can be substantially enriched for potential adaptations broad range realistic...
Recent empirical studies of taxa including humans, fish, and birds have shown elevated rates molecular evolution between species that diverged recently. Using the Moran model, we calculate expected divergence as a function time. Our findings suggest observed phenomenon at short timescales is consistent with standard population genetics theory. The apparent acceleration clock can be explained by segregating polymorphisms present time ancestral population, both neutral slightly deleterious,...
Epigenetically inherited aggregates of the yeast prion [PSI+] cause genomewide readthrough translation that sometimes increases evolvability in certain harsh environments. The effects natural selection on modifiers appearance have been subject much debate. It seems likely would be at least mildly deleterious most environments, but this may counteracted by its properties rare occasions. Indirect is predicted to depend primarily spontaneous rate, critical parameter has not previously...
Making genes into gene products is subject to predictable errors, each with a phenotypic effect that depends on normally cryptic sequence. Many sequences have strongly deleterious effects, for example when they cause protein misfolding. Strongly effects can be avoided globally by avoiding making errors (e.g., via proofreading machinery) or locally ensuring error has relatively benign effect. The local solution requires powerful selection acting every site and so evolves only in large...
Amino acid substitution models are a key component in phylogenetic analyses of protein sequences. All commonly used amino available to date time-reversible, an assumption designed for computational convenience but not biological reality. Another significant downside time-reversible is that they do allow inference rooted trees without outgroups. In this article, we introduce maximum likelihood approach nQMaker, extension the recently published QMaker method, allows estimation time...
Abstract Background selection describes the reduction in neutral diversity caused by against deleterious alleles at other loci. It is typically assumed that purging of affects linked variants, and indeed simulations only treat a genomic window. However, background unlinked loci also depresses diversity. In agreement with previous analytical approximations, our human-like genome realistically high genome-wide mutation rate, effects exceed those selection. reduces genetic factor independent...
“Fitness” quantifies the ability to survive and reproduce, but is operationalized in many different ways. Generally, short-term fitness (e.g., expected number of surviving offspring) assigned genotypes or phenotypes, used non-trivially derive longer-term operationalizations (e.g. fixation probability sojourn time), providing insight as which organismal strategies tend evolve due natural selection. Assigned vary, all summarize currently vital rates (i.e. births, deaths, growth). Derived...
Adaptive plasticity allows populations to adjust rapidly environmental change. If this is useful only rarely, may undergo mutational degradation and be lost from a population. We consider population of constant size N undergoing loss at functional mutation rate m with selective advantage s associated loss. Environmental change events occur theta per generation, killing all individuals that lack plasticity. The expected time until in fluctuating environment always least tau, the static...
Abstract Evolutionary capacitors phenotypically reveal a stock of cryptic genetic variation in reversible fashion. The sudden and revelation range is fundamentally different from the gradual introduction by mutation. Here I study invasion dynamics modifiers revelation. A modifier with optimal rate mopt has higher probability invading any other population than being counterinvaded. varies size N θ at which environmental change makes adaptive. For small populations less minimum cutoff Nmin,...
Abstract Phenotypic loss is an important evolutionary force in nature but the mechanism(s) responsible for remains unclear. We used both simulation and multiple-regression approaches to analyze data on of sporulation, a complex bacterial developmental process, during experimental evolution Bacillus subtilis. Neutral processes mutational degradation alone were sufficient explain loss-of-sporulation ability four five populations, while evidence that selection facilitated was found only one...
Biomarkers are important tools for diagnosis, prognosis, and identification of the causal factors physiological conditions. typically identified by correlating biological measurements with status a condition in sample subjects. Cross-sectional studies subjects at single timepoint, whereas longitudinal follow cohort through time. Identifying biomarkers aging is subject to unique challenges. Individuals who age faster have intrinsically higher mortality rates so preferentially lost over time,...
The extended evolutionary synthesis invokes a role for development in shaping adaptive evolution, which population genetics terms corresponds to mutation-biased adaptation. Critics have claimed that clonal interference makes adaptation rare. We consider the behaviour of two simultaneously adapting traits, one with larger mutation rate U, other selection coefficient s, using asexual travelling wave models. find is dominated by whichever trait has faster v isolation, subject stalling....
The long‐running debate about the role of selection in maintaining genetic variation has been given new impetus by discovery hundreds seasonally oscillating polymorphisms wild Drosophila, possibly stabilized an alternating summer‐winter regime. Historically, there skepticism potential temporal to balance polymorphism, because must be strong have a meaningful stabilizing effect—unless dominance also varies over time ("reversal dominance"). Here, we develop simplified model variable that...