Systematic bias in phylogenetic inference: Implications, Assessment, and Reduction

Molecular phylogenetic inference is the process of reconstructing relationships between individuals, species, or higher groups from genomic sequence data. The reliability of phylogenetic analysis relies on the fit between the substitution models used and the evolutionary processes that generated the data. In phylogenetic inference, we commonly use substitution models which assume that sequence evolution is stationary, reversible, and homogeneous (SRH). Many empirical and simulation studies have shown that assuming SRH conditions can lead to significant errors in phylogenetic inference when the data violates these assumptions. Yet, the extent of SRH violations and their effects on phylogenetic inference of tree topologies are not very well understood. In Chapter I, I introduced and applied the Maximal matched-pairs tests of homogeneity (MaxSym tests) to assess the scale and impact of SRH model violations on 3,572 partitions from 35 published phylogenetic data sets. I showed that roughly one-quarter of all the partitions I analysed reject the SRH assumptions and that for more than one-quarter of data sets, tree topologies inferred from all partitions differ significantly from topologies inferred using the subset of partitions that do not reject the SRH assumptions. In Chapter II, I simulated datasets under various degrees of non-SRH conditions using empirically derived parameters to mimic real data and examine the effects of incorrectly assuming SRH conditions on inferring phylogenies. I showed that maximum likelihood inference is generally quite robust to a wide range of SRH model violations but is inaccurate under extreme convergent evolution. In addition, I tested the power of the MaxSym tests and other popular tests to detect model violations due to non-SRH evolution. I showed that MaxSym tests performed well under the different schemes of simulations, and that of all the tests I studies, the MaxSym tests perform the best at identifying datasets that might mislead phylogenetic inference. In Chapter III, I investigated the ability of non-reversible models to estimate the root of a phylogeny. In addition, I introduced a new measure of support for the placement of the root in a phylogenetic tree, the rootstrap support. I tested the ability of nonreversible models to recover the root placement of five clades of mammals for which prior studies give very strong evidence of a particular root position. I showed that the nonreversible model correctly inferred the root of all the five clades with very high rootstrap support. I then applied the same approaches to infer the roots of two clades of mammals for which previous studies have repeatedly disagreed on the root position. I show that nonreversible models recover similar roots to previous studies, but the rootstrap support is lower than the other five clades. In Chapter IV, I investigated the homogeneity assumption widely used in phylogenetic inference. To check for homogeneity in empirical datasets, I introduced a computationally feasible test for homogeneity across lineages based on the AIC score. Using empirical datasets from three different clades of life I tested the homogeneity assumption by estimating amino-acid substitution matrices for monophyletic sub-clades within each dataset. I show that forcing the models to be homogenous always provides a worse fit to the data than allowing each sub-clade to have its own model. In addition, for every dataset, I found that a simpler model where two or more clades share the same substitution matrix is always better than the fully non-homogeneous model in terms of AIC score. Together, these chapters show the impact of model violation due to non-SRH evolution on phylogenetic inference and suggest the need to test for model violation prior to phylogenetic inference, or to develop and apply more complex substitution models to relax some of the assumptions associated with the most widely used models in phylogenetics

Reconstructing Biological and Digital Phylogenetic Trees in Parallel

In this paper, we study the parallel query complexity of reconstructing biological and digital phylogenetic trees from simple queries involving their nodes. This is motivated from computational biology, data protection, and computer security settings, which can be abstracted in terms of two parties, a responder, Alice, who must correctly answer queries of a given type regarding a degree-d tree, T, and a querier, Bob, who issues batches of queries, with each query in a batch being independent of the others, so as to eventually infer the structure of T. We show that a querier can efficiently reconstruct an n-node degree-d tree, T, with a logarithmic number of rounds and quasilinear number of queries, with high probability, for various types of queries, including relative-distance queries and path queries. Our results are all asymptotically optimal and improve the asymptotic (sequential) query complexity for one of the problems we study. Moreover, through an experimental analysis using both real-world and synthetic data, we provide empirical evidence that our algorithms provide significant parallel speedups while also improving the total query complexities for the problems we study

Platyrrhine Phylogenetics With A Focus On Callitrichine Life History Adaptations

The life history of a species is highly impacted by their reproductive strategy. In my dissertation I address the changing reproductive strategies in callitrichine New World monkeys and their genetic underpinnings using a phylogenetic approach. The necessity for a resolved phylogeny is universal to any comparative genomic study. Here we have constructed a reliable phylogenetic framework from which reproductive strategy could be studied in callitrichines. First, to determine the most recent common ancestor of Anthropoid primates we took a phylogenomic approach, using the publicly available whole genome sequences of 17 mammal species. With high confidence, we determined here that Tarsier is the most recent common ancestor to Anthropoid primates. Secondly, we construct a reliable phylogenetic framework for New World monkeys. To do this, genomic sequence databases are developed and parsed for non-genic markers. The resulting phylogeny is based on 40+kb of non-genic genomic data and contains 40 species. Finally the reproductive strategy of callitrichines was investigated. The timing and mechanism of litter size reduction in Goeldi\u27s monkey was accessed though detection of chimerism and adaptive evolution of genes involved in reproduction. We determined based on these analysis that the reduction in litter size is likely pre-ovulation and due to a reversion to mono-ovulation in the species

Phylogeny and evolutionary perspective of Opisthokonta protists

[cat] Per entendre l’origen dels Opistoconts (grup taxonòmic que conté animals, fongs i diversos llinatges protists emparentats) o inferir les seves transicions evolutives, és fonamental primer entendre les relacions filogenètiques entre les espècies existents en l’actualitat. La filogènia, particularment la filogenòmica, és el procediment vàlid per inferir relacions evolutives entre espècies, ja que la morfologia, les sinapomorfies moleculars o els canvis genètics singulars són arguments cíclics dependents del mostreig taxonòmic. Per aquesta raó hem fet servir dades genòmiques i transcriptòmiques per a construir un nou conjunt de dades format per dominis proteics de còpia única i els hem analitzat mitjançat diversos mètodes per prevenir errors sistemàtics. Hem pogut així confirmar la divisió entre Holomycota (Nucleariids, Opisthosporidia, quitridiomiciets i fongs) i Holozoa (Ichthyosporea, Filasterea, Choanomonada i Metazoa). També hem obtingut dades de RNAseq per situar espècies particularment ambigües com: Corallochytrium limacisporum la qual hem situat com a grup germà de Ichthyosporea, un altre grup holozou osmotròfic. Partint d’aquesta base filogenètica es pot començar a especular sobre les transicions evolutives entre els grups. No obstant, abans cal reconstruir els ancestres dels llinatges dels Opistoconts com també dels seus grups externs actuals: Apusomonadida i Breviatea. Els resultats indiquen que no existeix cap lligam definit entre els bacterívors ancestrals biflagelats (grup extern) i cap dels llinatges Opistoconts (grup d’interès). També que el darrer avantpassat comú dels Opistoconts probablement conservaria quasi tots els caràcters ancestrals com el moviment ameboide, filopodis, la fagotrofia, etc.; però seria uniflagel·lat, amb una forma cel·lular menys restringida pel tipus d’alimentació. Mitjançant la genòmica comparada hem estudiat les similituds entre grups no emparentats d’Opistoconts com els osmòtrofs amb paret cel·lular o les amebes filopodials nues. Per exemple, hem trobat que Ministeria vibrans (Filasterea) i C. limacisporum (Ichthyosporea) presenten un aparell flagel·lar fins ara desconegut amb un patró similar al que formen fongs i altres eucariotes. També que Ichthyosporea fa servir un material semblant a la quitina per construir la seva paret cel·lular. Aquestes similituds plantegen hipòtesis de convergència evolutiva o paral·lelisme entre llinatges propers que s’hauran de comprovar en un futur.[eng] To understand the origin of opisthokonts or infer evolutionary transitions within the group that contains two multicellular lineages (animals and fungi), it is first fundamental to understand the phylogenetic relationships between extant living species. Phylogeny and particularly phylogenomics (such the supermatrix approach) is the only valid procedure to infer evolutionary relationships between species, as morphological or molecular synapomorphies or rare genomic changes are cyclic arguments and really taxon dependent. This is why we have used genomic and transcriptomic data to build a novel dataset of Single Copy Protein Domains and test phylogenetic hypotheses with multiple methods to discard problems of systematic error. We have confirmed the division between Holomycota (Nucleariids, Opisthosporidia, chytrid fungi and fungi) and Holozoa (Ichthyosporea, Filasterea, Choanomonada and Metazoa). We also have generated RNAseq data to place a specially elusive species: Corallochytrium limacisporum and found it placed as sister group to Ichthyosporea, another osmotrophic holozoan group. With this solid phylogenetic background we can start to speculate on evolutionary transitions between groups, but not before reconstructing ancestral character states in different opisthokont lineages and also the extant living outgroups: Apusomonadida and Breviatea. So we conclude that there is no clear link between biflagellated free-living gliding bacterivores (outgroup) and any opisthokont lineage (ingroup). The Last Opisthokont Common Ancestor was probably uniflagellated but retained all other ancestral characters such amoeboid movement, filopodia, phagotrophy, etc. but had a less constrained cell shape or feeding mode. Then, we studied the similarities found between non-related groups of opisthokonts, such the walled osmotrophs or the naked filose amoebae through comparative genomics. For example, we found that Ministeria vibrans (Filasterea) and C. limacisporum (Ichthyosporea) have a flagellar apparatus previously unnoticed, and with a molecular pattern of flagellum reduction also seen in fungi and other eukaryotes. Also, Ichthyosporea probably use a chitin-like substance to build their cell wall (similar to fungi) but with an independently diversified pathway

Phylogeny of Geophagine cichlids from South America (Perciformes: Labroidei)

Three new species of cichlid fishes of the genus Geophagus, part of the Neotropical subfamily Geophaginae, are described from the Orinoco and Casiquiare drainages in Venezuela. Phylogenetic relationships among 16 genera and 30 species of Geophaginae are investigated using 136 morphological characters combined with DNA sequences coding for the mitochondrial gene NADH dehydrogenase subunit 4 (ND4) and the nuclear Recombination Activating Gene 2 (RAG2). Data from previous studies are integrated with the new dataset by incorporating published DNA sequences from the mitochondrial genes cytochrome b and 16S and the microsatellite flanking regions Tmo-M27 and Tmo-4C4. Total-evidence analysis revealed that Geophaginae is monophyletic and includes eighteen genera grouped into two major clades. In the first clade, the tribe Acarichthyini (genera Acarichthys and Guianacara) is sister-group to a clade in which Gymnogeophagus, 'Geophagus' steindachneri, and Geophagus sensu stricto are sister to 'Geophagus' brasiliensis and Mikrogeophagus; all these are in turn sister-group to Biotodoma, Dicrossus and Crenicara. In the second clade, Satanoperca, Apistogramma (including Apistogrammoides), and Taeniacara are sister to Crenicichla and Biotoecus. Monophyly and significantly short branches at the base of the phylogeny indicate that genera within Geophaginae differentiated rapidly within a relatively short period. High morphological, ecological, and behavioral diversity within the subfamily suggest that geophagine divergence may be the result of adaptive radiation

Evolutionary analysis of rapidly evolving RNA viruses

Recent advances in sequencing technology and computing power mean that we are in an unprecedented position to analyse large viral sequence datasets using state-of-the-art methods, with the aim of better understanding pathogen evolution and epidemiology. This thesis concerns the evolutionary analysis of rapidly evolving RNA viruses, with a focus on avian influenza and the use of Bayesian methodologies which account for uncertainty in the evolutionary process. As avian influenza viruses present an epidemiological and economic threat on a global scale, knowledge of how they are circulating and evolving is of substantial public health importance. In the first part of this thesis I consider avian influenza viruses of haemagglutinin (HA) subtype H7 which, along with H5, is the only subtype for which highly pathogenic influenza has been found. I conduct a comprehensive phylogenetic analysis of available H7 HA sequences to reveal global evolutionary relationships, which can help to target influenza surveillance in birds and facilitate the early detection of potential pandemic strains. I provide evidence for the continued distinction between American and Eurasian sequences, and suggest that the most likely route for the introduction of highly pathogenic H5N1 avian influenza to North America would be through the smuggling of caged birds. I proceed to apply novel methods to better understand the evolution of avian influenza. Firstly, I use an extension of stochastic mutational mapping methods to estimate the dN/dS ratio of H7 HA on different neuraminidase (NA) subtype backgrounds. I find dN/dS to be higher on the N2 NA background than on N1, N3 or N7 NA backgrounds, due to differences in selective pressure. Secondly, I investigate reassortment, which generates novel influenza strains and precedes human influenza pandemics. The rate at which reassortment occurs has been difficult to assess, and I take a novel approach to quantifying reassortment across phylogenies using discrete trait mapping methods. I also use discrete trait mapping to investigate inter-subtype recombination in early HIV-1 in Kinshasa, the epicentre of the HIV-1 group M epidemic. In the final section of the thesis, I describe a method whereby epidemiological parameters may be inferred from viral sequence data isolated from different infected individuals in a population. To conclude, I discuss the findings of this thesis in the context of other evolutionary and epidemiological studies, suggest future directions for avian influenza research and highlight scenarios in which the methods described in this thesis might find further application

Evolutionary genomics : statistical and computational methods

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

Evolutionary Genomics

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

Rol de la autofagia inducida por déficit nutricional en la briofita Physcomitrella patens.

Tesina (Grado en Ciencias Biológicas)--Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Lugar de Trabajo: Cátedra de Fisiología Vegetal. Facultad de Ciencias Exactas, Físicas y Naturales. Universidad Nacional de Córdoba. 2019. 56 h. con Anexos. tabls.; grafs. Contiene Referencia Bibliográfica.La autofagia es una de las principales vías de degradación de proteínas y componentes celulares y es un proceso fundamental para el mantenimiento de la homeostasis celular en organismos eucariotas. En plantas, diversos estudios con mutantes en los genes ATG (AuTophagic Genes) evidencian que defectos en la autofagia comprometen la viabilidad, crecimiento, desarrollo, productividad y respuestas a condiciones de estrés abiótico y biótico. Por otra parte, se observa sobrevida y mayor productividad cuando el proceso es aumentado con respecto a sus niveles normales. La utilización de Physcomitrella patens como modelo para el estudio de autofagia es recientes y se conoce poco en comparación con otros modelos vegetales. En este trabajo se aporta un análisis filogenético de las proteínas ATG8 de P. patens con respecto a otros organismos dentro del clado Viridiplantae, los resultados sugieren que la función se encuentra conservada dentro del grupo. Se realizó también un seguimiento de la evolución de la inducción del proceso en condiciones de déficit nutricional de Carbono y Nitrógeno, utilizando una línea reportera ATG8:GFP. También se estudió el efecto de estas mismas condiciones sobre líneas knockout para autofagia atg5 y atg7. Las mutantes resultaron hipersensibles al estrés y mostraron desbalances metabólicos en condiciones óptimas de crecimiento. Con este trabajo se demuestra que la autofagia cumple un rol fundamental en la supervivencia de P.patens frente al déficit de Carbono y Nitrógeno y se sientan las bases para estudiar autofagia en este musgo , que aporta una perspectiva innovadora por sus múltiples características