Publications by authors named "Wynn K Meyer"

8 Publications

  • Page 1 of 1

NCBI's Virus Discovery Codeathon: Building "FIVE" -The Federated Index of Viral Experiments API Index.

Viruses 2020 12 10;12(12). Epub 2020 Dec 10.

National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20894, USA.

Viruses represent important test cases for data federation due to their genome size and the rapid increase in sequence data in publicly available databases. However, some consequences of previously decentralized (unfederated) data are lack of consensus or comparisons between feature annotations. Unifying or displaying alternative annotations should be a priority both for communities with robust entry representation and for nascent communities with burgeoning data sources. To this end, during this three-day continuation of the Virus Hunting Toolkit codeathon series (VHT-2), a new integrated and federated viral index was elaborated. This Federated Index of Viral Experiments (FIVE) integrates pre-existing and novel functional and taxonomy annotations and virus-host pairings. Variability in the context of viral genomic diversity is often overlooked in virus databases. As a proof-of-concept, FIVE was the first attempt to include viral genome variation for HIV, the most well-studied human pathogen, through viral genome diversity graphs. As per the publication of this manuscript, FIVE is the first implementation of a virus-specific federated index of such scope. FIVE is coded in BigQuery for optimal access of large quantities of data and is publicly accessible. Many projects of database or index federation fail to provide easier alternatives to access or query information. To this end, a Python API query system was developed to enhance the accessibility of FIVE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v12121424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764237PMC
December 2020

RERconverge: an R package for associating evolutionary rates with convergent traits.

Bioinformatics 2019 11;35(22):4815-4817

Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Motivation: When different lineages of organisms independently adapt to similar environments, selection often acts repeatedly upon the same genes, leading to signatures of convergent evolutionary rate shifts at these genes. With the increasing availability of genome sequences for organisms displaying a variety of convergent traits, the ability to identify genes with such convergent rate signatures would enable new insights into the molecular basis of these traits.

Results: Here we present the R package RERconverge, which tests for association between relative evolutionary rates of genes and the evolution of traits across a phylogeny. RERconverge can perform associations with binary and continuous traits, and it contains tools for visualization and enrichment analyses of association results.

Availability And Implementation: RERconverge source code, documentation and a detailed usage walk-through are freely available at https://github.com/nclark-lab/RERconverge. Datasets for mammals, Drosophila and yeast are available at https://bit.ly/2J2QBnj.

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btz468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853647PMC
November 2019

Ancient convergent losses of yield potential risks for modern marine mammals.

Science 2018 08;361(6402):591-594

Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA.

Mammals diversified by colonizing drastically different environments, with each transition yielding numerous molecular changes, including losses of protein function. Though not initially deleterious, these losses could subsequently carry deleterious pleiotropic consequences. We have used phylogenetic methods to identify convergent functional losses across independent marine mammal lineages. In one extreme case, () accrued lesions in all marine lineages, while remaining intact in all terrestrial mammals. These lesions coincide with PON1 enzymatic activity loss in marine species' blood plasma. This convergent loss is likely explained by parallel shifts in marine ancestors' lipid metabolism and/or bloodstream oxidative environment affecting PON1's role in fatty acid oxidation. PON1 loss also eliminates marine mammals' main defense against neurotoxicity from specific man-made organophosphorus compounds, implying potential risks in modern environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.aap7714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317340PMC
August 2018

Evolutionary history inferred from the de novo assembly of a nonmodel organism, the blue-eyed black lemur.

Mol Ecol 2015 Sep 24;24(17):4392-405. Epub 2015 Aug 24.

Department of Human Genetics, University of Chicago, Chicago, IL, 60637, USA.

Lemurs, the living primates most distantly related to humans, demonstrate incredible diversity in behaviour, life history patterns and adaptive traits. Although many lemur species are endangered within their native Madagascar, there is no high-quality genome assembly from this taxon, limiting population and conservation genetic studies. One critically endangered lemur is the blue-eyed black lemur Eulemur flavifrons. This species is fixed for blue irises, a convergent trait that evolved at least four times in primates and was subject to positive selection in humans, where 5' regulatory variation of OCA2 explains most of the brown/blue eye colour differences. We built a de novo genome assembly for E. flavifrons, providing the most complete lemur genome to date, and a high confidence consensus sequence for close sister species E. macaco, the (brown-eyed) black lemur. From diversity and divergence patterns across the genomes, we estimated a recent split time of the two species (160 Kya) and temporal fluctuations in effective population sizes that accord with known environmental changes. By looking for regions of unusually low diversity, we identified potential signals of directional selection in E. flavifrons at MITF, a melanocyte development gene that regulates OCA2 and has previously been associated with variation in human iris colour, as well as at several other genes involved in melanin biosynthesis in mammals. Our study thus illustrates how whole-genome sequencing of a few individuals can illuminate the demographic and selection history of nonmodel species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/mec.13327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557055PMC
September 2015

The convergent evolution of blue iris pigmentation in primates took distinct molecular paths.

Am J Phys Anthropol 2013 Jul 2;151(3):398-407. Epub 2013 May 2.

Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.

How many distinct molecular paths lead to the same phenotype? One approach to this question has been to examine the genetic basis of convergent traits, which likely evolved repeatedly under a shared selective pressure. We investigated the convergent phenotype of blue iris pigmentation, which has arisen independently in four primate lineages: humans, blue-eyed black lemurs, Japanese macaques, and spider monkeys. Characterizing the phenotype across these species, we found that the variation within the blue-eyed subsets of each species occupies strongly overlapping regions of CIE L*a*b* color space. Yet whereas Japanese macaques and humans display continuous variation, the phenotypes of blue-eyed black lemurs and their sister species (whose irises are brown) occupy more clustered subspaces. Variation in an enhancer of OCA2 is primarily responsible for the phenotypic difference between humans with blue and brown irises. In the orthologous region, we found no variant that distinguishes the two lemur species or associates with quantitative phenotypic variation in Japanese macaques. Given the high similarity between the blue iris phenotypes in these species and that in humans, this finding implies that evolution has used different molecular paths to reach the same end.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajpa.22280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746105PMC
July 2013

Revisiting an old riddle: what determines genetic diversity levels within species?

PLoS Biol 2012 11;10(9):e1001388. Epub 2012 Sep 11.

Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.

Understanding why some species have more genetic diversity than others is central to the study of ecology and evolution, and carries potentially important implications for conservation biology. Yet not only does this question remain unresolved, it has largely fallen into disregard. With the rapid decrease in sequencing costs, we argue that it is time to revive it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pbio.1001388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439417PMC
June 2013

Evaluating the evidence for transmission distortion in human pedigrees.

Genetics 2012 May 29;191(1):215-32. Epub 2012 Feb 29.

Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.

Children of a heterozygous parent are expected to carry either allele with equal probability. Exceptions can occur, however, due to meiotic drive, competition among gametes, or viability selection, which we collectively term "transmission distortion" (TD). Although there are several well-characterized examples of these phenomena, their existence in humans remains unknown. We therefore performed a genome-wide scan for TD by applying the transmission disequilibrium test (TDT) genome-wide to three large sets of human pedigrees of European descent: the Framingham Heart Study (FHS), a founder population of European origin (HUTT), and a subset of the Autism Genetic Resource Exchange (AGRE). Genotyping error is an important confounder in this type of analysis. In FHS and HUTT, despite extensive quality control, we did not find sufficient evidence to exclude genotyping error in the strongest signals. In AGRE, however, many signals extended across multiple SNPs, a pattern highly unlikely to arise from genotyping error. We identified several candidate regions in this data set, notably a locus in 10q26.13 displaying a genome-wide significant TDT in combined female and male transmissions and a signature of recent positive selection, as well as a paternal TD signal in 6p21.1, the same region in which a significant TD signal was previously observed in 30 European males. Neither region replicated in FHS, however, and the paternal signal was not visible in sperm competition assays or as allelic imbalance in sperm. In maternal transmissions, we detected no strong signals near centromeres or telomeres, the regions predicted to be most susceptible to female-specific meiotic drive, but we found a significant enrichment of top signals among genes involved in cell junctions. These results illustrate both the potential benefits and the challenges of using the TDT to study transmission distortion and provide candidates for investigation in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1534/genetics.112.139576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338262PMC
May 2012

Evolutionary genetics of the human Rh blood group system.

Hum Genet 2012 Jul 25;131(7):1205-16. Epub 2012 Feb 25.

Department of Anthropology, Pennsylvania State University, University Park, PA 16801, USA.

The evolutionary history of variation in the human Rh blood group system, determined by variants in the RHD and RHCE genes, has long been an unresolved puzzle in human genetics. Prior to medical treatments and interventions developed in the last century, the D-positive (RhD positive) children of D-negative (RhD negative) women were at risk for hemolytic disease of the newborn, if the mother produced anti-D antibodies following sensitization to the blood of a previous D-positive child. Given the deleterious fitness consequences of this disease, the appreciable frequencies in European populations of the responsible RHD gene deletion variant (for example, 0.43 in our study) seem surprising. In this study, we used new molecular and genomic data generated from four HapMap population samples to test the idea that positive selection for an as-of-yet unknown fitness benefit of the RHD deletion may have offset the otherwise negative fitness effects of hemolytic disease of the newborn. We found no evidence that positive natural selection affected the frequency of the RHD deletion. Thus, the initial rise to intermediate frequency of the RHD deletion in European populations may simply be explained by genetic drift/founder effect, or by an older or more complex sweep that we are insufficiently powered to detect. However, our simulations recapitulate previous findings that selection on the RHD deletion is frequency dependent and weak or absent near 0.5. Therefore, once such a frequency was achieved, it could have been maintained by a relatively small amount of genetic drift. We unexpectedly observed evidence for positive selection on the C allele of RHCE in non-African populations (on chromosomes with intact copies of the RHD gene) in the form of an unusually high F( ST ) value and the high frequency of a single haplotype carrying the C allele. RhCE function is not well understood, but the C/c antigenic variant is clinically relevant and can result in hemolytic disease of the newborn, albeit much less commonly and severely than that related to the D-negative blood type. Therefore, the potential fitness benefits of the RHCE C allele are currently unknown but merit further exploration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00439-012-1147-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378649PMC
July 2012