Bielawski, Joe
Permanent URI for this collectionhttps://hdl.handle.net/10222/22290
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Item Open Access Methods for selecting fixed-effect models for heterogeneous codon evolution, with comments on their application to gene and genome data(2007) Bao, Le; Gu, Hong; Dunn, Katherine A.; Bielawski, Joseph P.Background: Models of codon evolution have proven useful for investigating the strength and direction of natural selection. In some cases, a priori biological knowledge has been used successfully to model heterogeneous evolutionary dynamics among codon sites. These are called fixed-effect models, and they require that all codon sites are assigned to one of several partitions which are permitted to have independent parameters for selection pressure, evolutionary rate, transition to transversion ratio or codon frequencies. For single gene analysis, partitions might be defined according to protein tertiary structure, and for multiple gene analysis partitions might be defined according to a gene's functional category. Given a set of related fixed-effect models, the task of selecting the model that best fits the data is not trivial. Results: In this study, we implement a set of fixed-effect codon models which allow for different levels of heterogeneity among partitions in the substitution process. We describe strategies for selecting among these models by a backward elimination procedure, Akaike information criterion ( AIC) or a corrected Akaike information criterion ( AICc). We evaluate the performance of these model selection methods via a simulation study, and make several recommendations for real data analysis. Our simulation study indicates that the backward elimination procedure can provide a reliable method for model selection in this setting. We also demonstrate the utility of these models by application to a single-gene dataset partitioned according to tertiary structure ( abalone sperm lysin), and a multi-gene dataset partitioned according to the functional category of the gene ( flagellar-related proteins of Listeria). Conclusion: Fixed-effect models have advantages and disadvantages. Fixed-effect models are desirable when data partitions are known to exhibit significant heterogeneity or when a statistical test of such heterogeneity is desired. They have the disadvantage of requiring a priori knowledge for partitioning sites. We recommend: ( i) selection of models by using backward elimination rather than AIC or AICc, ( ii) use a stringent cut-off, e. g., p = 0.0001, and ( iii) conduct sensitivity analysis of results. With thoughtful application, fixed- effect codon models should provide a useful tool for large scale multi-gene analyses.Item Open Access Prevalence and evolution of core photosystem II genes in marine cyanobacterial viruses and their hosts(2006-08) Sullivan, Matthew B.; Lindell, Debbie; Lee, Jessica A.; Thompson, Luke R.; Bielawski, Joseph P.; Chisholm, Sallie W.Cyanophages ( cyanobacterial viruses) are important agents of horizontal gene transfer among marine cyanobacteria, the numerically dominant photosynthetic organisms in the oceans. Some cyanophage genomes carry and express host-like photosynthesis genes, presumably to augment the host photosynthetic machinery during infection. To study the prevalence and evolutionary dynamics of this phenomenon, 33 cultured cyanophages of known family and host range and viral DNA from field samples were screened for the presence of two core photosystem reaction center genes, psbA and psbD. Combining this expanded dataset with published data for nine other cyanophages, we found that 88% of the phage genomes contain psbA, and 50% contain both psbA and psbD. The psbA gene was found in all myoviruses and Prochlorococcus podoviruses, but could not be amplified from Prochlorococcus siphoviruses or Synechococcus podoviruses. Nearly all of the phages that encoded both psbA and psbD had broad host ranges. We speculate that the presence or absence of psbA in a phage genome may be determined by the length of the latent period of infection. Whether it also carries psbD may reflect constraints on coupling of viral- and host-encoded PsbA-PsbD in the photosynthetic reaction center across divergent hosts. Phylogenetic clustering patterns of these genes from cultured phages suggest that whole genes have been transferred from host to phage in a discrete number of events over the course of evolution ( four for psbA, and two for psbD), followed by horizontal and vertical transfer between cyanophages. Clustering patterns of psbA and psbD from Synechococcus cells were inconsistent with other molecular phylogenetic markers, suggesting genetic exchanges involving Synechococcus lineages. Signatures of intragenic recombination, detected within the cyanophage gene pool as well as between hosts and phages in both directions, support this hypothesis. The analysis of cyanophage psbA and psbD genes from field populations revealed significant sequence diversity, much of which is represented in our cultured isolates. Collectively, these findings show that photosynthesis genes are common in cyanophages and that significant genetic exchanges occur from host to phage, phage to host, and within the phage gene pool. This generates genetic diversity among the phage, which serves as a reservoir for their hosts, and in turn influences photosystem evolution.Item Open Access Multilocus Genotyping Assays for Single Nucleotide Polymorphism-Based Subtyping of Listeria monocytogenes Isolates(2008-12) Ward, Todd J.; Ducey, Thomas F.; Usgaard, Thomas; Dunn, Katherine A.; Bielawski, Joseph P.Listeria monocytogenes is responsible for serious invasive illness associated with consumption of contaminated food and places a significant burden on public health and the agricultural economy. We recently developed a multilocus genotyping ( MLGT) assay for high-throughput subtype determination of L. monocytogenes lineage I isolates based on interrogation of single nucleotide polymorphisms ( SNPs) via multiplexed primer extension reactions. Here we report the development and validation of two additional MLGT assays that address the need for comprehensive DNA sequence-based subtyping of L. monocytogenes. The first of these novel MLGT assays targeted variation segregating within lineage II, while the second assay combined probes for lineage III strains with probes for strains representing a recently characterized fourth evolutionary lineage (IV) of L. monocytogenes. These assays were based on nucleotide variation identified in >3.8 Mb of comparative DNA sequence and consisted of 115 total probes that differentiated 93% of the 100 haplotypes defined by the multilocus sequence data. MLGT reproducibly typed the 173 isolates used in SNP discovery, and the 10,448 genotypes derived from MLGT analysis of these isolates were consistent with DNA sequence data. Application of the MLGT assays to assess subtype prevalence among isolates from ready-to-eat foods and food-processing facilities indicated a low frequency (6.3%) of epidemic clone subtypes and a substantial population of isolates (>30%) harboring mutations in inlA associated with attenuated virulence in cell culture and animal models. These mutations were restricted to serogroup 1/2 isolates, which may explain the overrepresentation of serotype 4b isolates in human listeriosis cases.Item Open Access Phylogenomic analysis of natural selection pressure in Streptococcus genomes(2007-08) Anisimova, Maria; Bielawski, Joseph P.; Dunn, Katherine; Yang, ZihengBackground: In comparative analyses of bacterial pathogens, it has been common practice to discriminate between two types of genes: (i) those shared by pathogens and their non-pathogenic relatives (core genes), and (ii) those found exclusively in pathogens (pathogen-specific accessory genes). Rather than attempting to a priori delineate genes into sets more or less relevant to pathogenicity, we took a broad approach to the analysis of Streptococcus species by investigating the strength of natural selection in all clusters of homologous genes. The genus Streptococcus is comprised of a wide variety of both pathogenic and commensal lineages, and we relate our findings to the pre-existing knowledge of Streptococcus virulence factors. Results: Our analysis of 1730 gene clusters revealed 136 cases of positive Darwinian selection, which we suggest is most likely to result from an antagonistic interaction between the host and pathogen at the molecular level. A two-step validation procedure suggests that positive selection was robustly identified in our genomic survey. We found no evidence to support the notion that pathogen specific accessory genes are more likely to be subject to positive selection than core genes. Indeed, we even uncovered a few cases of essential gene evolution by positive selection. Among the gene clusters subject to positive selection, a large fraction (29%) can be connected to virulence. The most striking finding was that a considerable fraction of the positively selected genes are also known to have tissue specific patterns of expression during invasive disease. As current expression data is far from comprehensive, we suggest that this fraction was underestimated. Conclusion: Our findings suggest that pathogen specific genes, although a popular focus of research, do not provide a complete picture of the evolutionary dynamics of virulence. The results of this study, and others, support the notion that the products of both core and accessory genes participate in complex networks that comprise the molecular basis of virulence. Future work should seek to understand the evolutionary dynamics of both core and accessory genes as a function of the networks in which they participate.Item Open Access Improving Evolutionary Models for Mitochondrial Protein Data with Site-Class Specific Amino Acid Exchangeability Matrices(2013-01) Dunn, Katherine A.; Jiang, Wenyi; Field, Christopher; Bielawski, Joseph P.Adequate modeling of mitochondrial sequence evolution is an essential component of mitochondrial phylogenomics (comparative mitogenomics). There is wide recognition within the field that lineage-specific aspects of mitochondrial evolution should be accommodated through lineage-specific amino-acid exchangeability matrices (e.g., mtMam for mammalian data). However, such a matrix must be applied to all sites and this implies that all sites are subject to the same, or largely similar, evolutionary constraints. This assumption is unjustified. Indeed, substantial differences are expected to arise from three-dimensional structures that impose different physiochemical environments on individual amino acid residues. The objectives of this paper are (1) to investigate the extent to which amino acid evolution varies among sites of mitochondrial proteins, and (2) to assess the potential benefits of explicitly modeling such variability. To achieve this, we developed a novel method for partitioning sites based on amino acid physiochemical properties. We apply this method to two datasets derived from complete mitochondrial genomes of mammals and fish, and use maximum likelihood to estimate amino acid exchangeabilities for the different groups of sites. Using this approach we identified large groups of sites evolving under unique physiochemical constraints. Estimates of amino acid exchangeabilities differed significantly among such groups. Moreover, we found that joint estimates of amino acid exchangeabilities do not adequately represent the natural variability in evolutionary processes among sites of mitochondrial proteins. Significant improvements in likelihood are obtained when the new matrices are employed. We also find that maximum likelihood estimates of branch lengths can be strongly impacted. We provide sets of matrices suitable for groups of sites subject to similar physiochemical constraints, and discuss how they might be used to analyze real data. We also discuss how the general approach might be employed to improve a variety of mitogenomic-based research activities.Item Open Access Positive Darwinian Selection in the Piston That Powers Proton Pumps in Complex I of the Mitochondria of Pacific Salmon(2011-09) Garvin, Michael R.; Bielawski, Joseph P.; Gharrett, Anthony J.The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.