Phylogenetic Tree Reconstruction Accuracy and Model Fit when Proportions of Variable Sites Change across the Tree

Commonly used phylogenetic models assume a homogeneous process through time in all parts of the tree. However, it is known that these models can be too simplistic as they do not account for nonhomogeneous lineage-specific properties. In particular, it is now widely recognized that as constraints on sequences evolve, the proportion and positions of variable sites can vary between lineages causing heterotachy. The extent to which this model misspecification affects tree reconstruction is still unknown. Here, we evaluate the effect of changes in the proportions and positions of variable sites on model fit and tree estimation. We consider 5 current models of nucleotide sequence evolution in a Bayesian Markov chain Monte Carlo framework as well as maximum parsimony (MP). We show that for a tree with 4 lineages where 2 nonsister taxa undergo a change in the proportion of variable sites tree reconstruction under the best-fitting model, which is chosen using a relative test, often results in the wrong tree. In this case, we found that an absolute test of model fit is a better predictor of tree estimation accuracy. We also found further evidence that MP is not immune to heterotachy. In addition, we show that increased sampling of taxa that have undergone a change in proportion and positions of variable sites is critical for accurate tree reconstruction

Systematic Error in Seed Plant Phylogenomics

Resolving the closest relatives of Gnetales has been an enigmatic problem in seed plant phylogeny. The problem is known to be difficult because of the extent of divergence between this diverse group of gymnosperms and their closest phylogenetic relatives. Here, we investigate the evolutionary properties of conifer chloroplast DNA sequences. To improve taxon sampling of Cupressophyta (non-Pinaceae conifers), we report sequences from three new chloroplast (cp) genomes of Southern Hemisphere conifers. We have applied a site pattern sorting criterion to study compositional heterogeneity, heterotachy, and the fit of conifer chloroplast genome sequences to a general time reversible + G substitution model. We show that non-time reversible properties of aligned sequence positions in the chloroplast genomes of Gnetales mislead phylogenetic reconstruction of these seed plants. When 2,250 of the most varied sites in our concatenated alignment are excluded, phylogenetic analyses favor a close evolutionary relationship between the Gnetales and Pinaceae—the Gnepine hypothesis. Our analytical protocol provides a useful approach for evaluating the robustness of phylogenomic inferences. Our findings highlight the importance of goodness of fit between substitution model and data for understanding seed plant phylogeny

Quartet Sampling distinguishes lack of support from conflicting support in the green plant tree of life

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143738/1/ajb21016-sup-0009-AppendixS9.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143738/2/ajb21016.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143738/3/ajb21016-sup-0004-AppendixS4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143738/4/ajb21016-sup-0001-AppendixS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143738/5/ajb21016-sup-0002-AppendixS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143738/6/ajb21016_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143738/7/ajb21016-sup-0005-AppendixS5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143738/8/ajb21016-sup-0006-AppendixS6.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143738/9/ajb21016-sup-0008-AppendixS8.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143738/10/ajb21016-sup-0003-AppendixS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143738/11/ajb21016-sup-0007-AppendixS7.pd

Lineage specific evolution and phylogenetic analysis : a thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomathematics at Massey University, Palmerston North, New Zealand

Phylogenetic models generally assume a homogeneous, time reversible, stationary process. These assumptions are often violated by the real, far more complex, evolutionary process. This thesis is centered on non-homogeneous, lineage-specific, properties of molecular sequences. It consist several related but independent studies. LineageSpecificSeqgen, an extension to the Seq-Gen program, which allows generation of sequences with changes in the proportion of variable sites, is introduced. This program is then used in a simulation study showing that changes in the proportion of variable sites can hinder tree estimation accuracy, and that tree reconstruction under the best-fit model chosen using a relative test can result in a wrong tree. In this case, the less commonly used absolute model-fit was a better predictor of tree estimation accuracy. This study found that increased taxon sampling of lineages that have undergone a change in the proportion of variable sites was critical for accurate tree reconstruction and that, in contrast to some earlier findings, the accuracy of maximum parsimony is adversely affected by such changes. This thesis also addresses the well-known long-branch attraction artifact. A nonparametric bootstrap test to identify changes in the substitution process is introduced, validated, and applied to the case of Microsporidia, a highly reduced intracellular parasite. Microsporidia was first thought to be an early branching eukaryote, but is now believed to be sister to, or included within, fungi. Its apparent basal eukaryote position is considered a result of long-branch attraction due to an elevated evolutionary rate in the microsporidian lineage. This study shows that long-branch estimates and basal positioning of Microsporidia both correlate with increased proportions of radical substitutions in the microsporidian lineage. In simulated data, such increased proportions of radical substitutions leads to erroneous long-branch estimates. These results suggest that the long microsporidian branch is likely to be a result of an increased proportion of radical substitutions on that branch, rather than increased evolutionary rate per se. The focus of the last study is the intriguing case of Mesostigma, a fresh water green alga for which contradicting phylogenetic relationships were inferred. While some studies placed Mesostigma within the Streptophyta lineage (which includes land plants), others placed it as the deepest green algae divergence. This basal positioning is regarded as a result of long-branch attraction due to poor taxon sampling. Reinvestigation of a 13- taxon mitochondrial amino acid dataset and a sub-dataset of 8 taxa reveals that site sampling, and in particular the treatment of missing data, is just as important a factor for accurate tree reconstruction as taxon sampling. This study identifies a difficulty in recreating the long-branch attraction observed for the 8-taxon dataset in simulated data. The cause is likely to be the smaller number of amino acid characters per site in simulated data compared to real data, highlighting the fact that there are properties of the evolutionary process that are yet to be accurately modeled

Labour productivity and technology heterogeneity

Background: Commonly used phylogenetic models assume a homogeneous evolutionary process throughout the tree. It is known that these homogeneous models are often too simplistic, and that with time some properties of the evolutionary process can change (due to selection or drift). In particular, as constraints on sequences evolve, the proportion of variable sites can vary between lineages. This affects the ability of phylogenetic methods to correctly estimate phylogenetic trees, especially for long timescales. To date there is no phylogenetic model that allows for change in the proportion of variable sites, and the degree to which this affects phylogenetic reconstruction is unknown. Results: We present LineageSpecificSeqgen, an extension to the seq-gen program that allows generation of sequences with both changes in the proportion of variable sites and changes in the rate at which sites switch between being variable and invariable. In contrast to seq-gen and its derivatives to date, we interpret branch lengths as the mean number of substitutions per variable site, as opposed to the mean number of substitutions per site (which is averaged over all sites, including invariable sites). This allows specification of the substitution rates of variable sites, independently of the proportion of invariable sites. Conclusion: LineageSpecificSeqgen allows simulation of DNA and amino acid sequence alignments under a lineage-specific evolutionary process. The program can be used to test current models of evolution on sequences that have undergone lineage-specific evolution. It facilitates the development of both new methods to identify such processes in real data, and means to account for such processes. The program is available at: http://awcmee.massey.ac.nz/downloads.htm

Nitric oxide charged catheters as a potential strategy for prevention of hospital acquired infections

<div><p>Background</p><p>Catheter-Associated Hospital-Acquired Infections (HAI's) are caused by biofilm-forming bacteria. Using a novel approach, we generated anti-infective barrier on catheters by charging them with Nitric Oxide (NO), a naturally-produced gas molecule. NO is slowly released from the catheter upon contact with physiological fluids, and prevents bacterial colonization and biofilm formation onto catheter surfaces.</p><p>Aims and methods</p><p>The aim of the study was to assess the anti-infective properties of NO-charged catheters exposed to low concentration (up to 10³ CFU/ml) of microbial cells <i>in-vitro</i>. We assessed NO-charged tracheal tubes using <i>Pseudomonas aeruginosa</i>, dialysis and biliary catheters using <i>Escherichia coli</i>, and urinary catheters using <i>E</i>. <i>coli</i>, <i>Candida albicans</i> or <i>Enterococcus faecalis</i>. Safety and tolerability of NO-charged urinary catheters were evaluated in a phase 1 clinical study in 12 patients. Six patients were catheterized with NO-charged catheters (NO-group), followed by 6 patients catheterized with regular control catheters (CT-group). Comparison of safety parameters between the study groups was performed.</p><p>Results</p><p>NO-charged tracheal, dialysis biliary and urinary catheters prevented <i>P</i>. <i>aerugino</i>sa, <i>E</i>. <i>coli</i> and <i>C</i>. <i>albicans</i> attachment and colonization onto their surfaces and eradicated corresponding planktonic microbial cells in the surrounding media after 24–48 hours, while <i>E</i>. <i>faecalis</i> colonization onto urinary catheters was reduced by 1 log compared to controls. All patients catheterized with an NO-charged urinary catheter successfully completed the study without experiencing NO-related AE's or serious AE's (SAE's).</p><p>Conclusion</p><p>These data highlight the potential of NO-based technology as potential platform for preventing catheter-associated HAI's.</p></div