Biology subjects

David J Winter

Publications and source records attributed to David J Winter.

4 recordsLinked to original sources

bioRxiv2016

The genealogical sorting index and species delimitation

The Genealogical Sorting Index (gsi) has been widely used in species-delimitation studies, where it is usually interpreted as a measure of the degree to which each of several predefined groups of specimens display a pattern of divergent evolution in a phylogenetic tree. Here we show that the gsi value obtained for a given group is highly dependent on the structure of the tree outside of the group of interest. By calculating the gsi from simulated datasets we demonstrate this dependence undermines some of desirable properties of the statistic. We also review the use of the gsi delimitation studies, and show that the gsi has typically been used under scenarios in which it is expected to produce large and statistically significant results for samples that are not divergent from all other populations and thus should not be considered species. Our proposed solution to this problem performs better than the gsi in under these conditions. Nevertheless, we show that our modified approach can produce positive results for populations that are connected by substantial levels of gene flow, and are thus unlikely to represent distinct species. We stress that the properties of gsi made clear in this manuscript must be taken into account if the statistic is used in species-delimitation studies. More generally, we argue that the results of genetic species-delimitation methods need to be interpreted in the light the biological and ecological setting of a study, and not treated as the final test applied to hypotheses generated by other data.

Evolutionary Biology↗

bioRxiv2015

Estimating error models for whole genome sequencing using mixtures of Dirichlet-multinomial distributions

MotivationAccurate identification of genotypes is critical in identifying de novo mutations, linking mutations with disease, and determining mutation rates. Because de novo mutations are rare, even low levels of genotyping error can cause a large fraction of false positive de novo mutations. Biological and technical processes that adversely affect genotyping include copy-number-variation, paralogous sequences, library preparation, sequencing error, and reference-mapping biases, among others.\n\nResultsWe modeled the read depth for all data as a mixture of Dirichlet-multinomial distributions, resulting in significant improvements over previously used models. In most cases the best model was comprised of two distributions. The major-component distribution is similar to a binomial distribution with low error and low reference bias. The minor-component distribution is overdispersed with higher error and reference bias. We also found that sites fitting the minor component are enriched for copy number variants and low complexity region. We expect that this approach to modeling the distribution of NGS data, will lead to improved genotyping. For example, this approach provides an expected distribution of reads that can be incorporated into a model to estimate de novo mutations using reads across a pedigree.\n\nAvailabilityMethods and data files are available at https://github.com/CartwrightLab/WuEtAl2016/.\n\nContactcartwright@asu.edu

Genomics↗

bioRxiv2015

Low base-substitution mutation rate in the germline genome of ciliate Tetrahymena thermophila

Mutation is the ultimate source of all genetic variation and is, therefore, central to evolutionary change. Previous work on Paramecium tetraurelia found an unusually low germline base-substitution mutation rate in this ciliate. Here, we tested the generality of this result among ciliates using Tetrahymena thermophila. We sequenced the genomes of 10 lines of T. thermophila that had each undergone approximately 1,000 generations of mutation accumulation (MA). We applied an existing mutation-calling pipeline and developed a new probabilistic mutation detection approach that directly models the design of an MA experiment and accommodates the noise introduced by mismapped reads. Our probabilistic mutation-calling method provides a straightforward way of estimating the number of sites at which a mutation could have been called if one was present, providing the denominator for our mutation rate calculations. From these methods, we find that T. thermophila has a germline base-substitution mutation rate of 7.61 x 10-12 per site, per cell division, which is consistent with the low base-substitution mutation rate in P. tetraurelia. Over the course of the evolution experiment, genomic exclusion lines derived from the MA lines experienced a fitness decline that cannot be accounted for by germline base-substitution mutations alone, suggesting that other genetic or epigenetic factors must be involved. Because selection can only operate to reduce mutation rates based upon the \"visible\" mutational load, asexual reproduction with a transcriptionally silent germline may allow ciliates to evolve extremely low germline mutation rates.

Evolutionary Biology↗

bioRxiv2015

Whole genome sequencing of field isolates reveals extensive genetic diversity in Plasmodium vivax from Colombia

Plasmodium vivax is the most prevalent malarial species in South America and exerts a substantial burden on the populations it affects. The control and eventual elimination of P. vivax are global health priorities. Genomic research contributes to this objective by improving our understanding of the biology of P. vivax and through the development of new genetic markers that can be used to monitor efforts to reduce malaria transmission.\n\nHere we analyze whole-genome data from eight field samples from a region in Cordoba, Colombia where malaria is endemic. We find considerable genetic diversity within this population, a result that contrasts with earlier studies suggesting that P. vivax had limited diversity in the Americas. We also identify a selective sweep around a substitution known to confer resistance to sulphadoxine-pyrimethamine (SP). This is the first observation of a selective sweep for SP resistance in this species. These results indicate that P. vivax has been exposed to SP pressure even when the drug is not in use as a first line treatment for patients afflicted by this parasite. We identify multiple non-synonymous substitutions in three other genes known to be involved with drug resistance in Plasmodium species. Finally, we found extensive microsatellite polymorphisms. Using this information we developed 18 polymorphic and easy to score microsatellite loci that can be used in epidemiological investigations in South America.\n\nAuthor SummaryAlthough P. vivax is not as deadly as the more widely studied P. falciparum, it remains a pressing global health problem. Here we report the results of a whole-genome study of P. vivax from Cordoba, Colombia, in South America. This parasite is the most prevalent in this region. We show that the parasite population is genetically diverse, which is contrary to expectations from earlier studies from the Americas. We also find molecular evidence that resistance to an anti-malarial drug has arisen recently in this region. This selective sweep indicates that the parasite has been exposed to a drug that is not used as first-line treatment for this malaria parasite. In addition to extensive single nucleotide and microsatellite polymorphism, we report 18 new genetic loci that might be helpful for fine-scale studies of this species in the Americas.

Genomics↗