Greedy Selection of Species for Ancestral State Reconstruction on Phylogenies: Elimination Is Better than Insertion

Accurate reconstruction of ancestral character states on a phylogeny is crucial in many genomics studies. We study how to select species to achieve the best reconstruction of ancestral character states on a phylogeny. We first show that the marginal maximum likelihood has the monotonicity property that more taxa give better reconstruction, but the Fitch method does not have it even on an ultrametric phylogeny. We further validate a greedy approach for species selection using simulation. The validation tests indicate that backward greedy selection outperforms forward greedy selection. In addition, by applying our selection strategy, we obtain a set of the ten most informative species for the reconstruction of the genomic sequence of the so-called boreoeutherian ancestor of placental mammals. This study has broad relevance in comparative genomics and paleogenomics since limited research resources do not allow researchers to sequence the large number of descendant species required to reconstruct an ancestral sequence.     

Ancestral State Reconstruction Reveals Rampant Homoplasy of Diagnostic Morphological Characters in Urticaceae,Conflicting with Current Classification Schemes

Urticaceae is a family with more than 2000 species, which contains remarkable morphological diversity. It has undergone many taxonomic reorganizations, and is currently the subject of further systematic studies. To gain more resolution in systematic studies and to better understand the general patterns of character evolution in Urticaceae, based on our previous phylogeny including 169 accessions comprising 122 species across 47 Urticaceae genera, we examined 19 diagnostic characters, and analysed these employing both maximum-parsimony and maximum-likelihood approaches. Our results revealed that 16 characters exhibited multiple state changes within the family, with ten exhibiting >eight changes and three exhibiting between 28 and 40. Morphological synapomorphies were identified for many clades, but the diagnostic value of these was often limited due to reversals within the clade and/or homoplasies elsewhere. Recognition of the four clades comprising the family at subfamily level can be supported by a small number carefully chosen defining traits for each. Several non-monophyletic genera appear to be defined only by characters that are plesiomorphic within their clades, and more detailed work would be valuable to find defining traits for monophyletic clades within these. Some character evolution may be attributed to adaptive evolution in Urticaceae due to shifts in habitat or vegetation type. This study demonstrated the value of using phylogeny to trace character evolution, and determine the relative importance of morphological traits for classification.     

Evolutionary History of Assassin Bugs (Insecta: Hemiptera: Reduviidae): Insights from Divergence Dating and Ancestral State Reconstruction

Assassin bugs are one of the most successful clades of predatory animals based on their species numbers (∼6,800 spp.) and wide distribution in terrestrial ecosystems. Various novel prey capture strategies and remarkable prey specializations contribute to their appeal as a model to study evolutionary pathways involved in predation. Here, we reconstruct the most comprehensive reduviid phylogeny (178 taxa, 18 subfamilies) to date based on molecular data (5 markers). This phylogeny tests current hypotheses on reduviid relationships emphasizing the polyphyletic Reduviinae and the blood-feeding, disease-vectoring Triatominae, and allows us, for the first time in assassin bugs, to reconstruct ancestral states of prey associations and microhabitats. Using a fossil-calibrated molecular tree, we estimated divergence times for key events in the evolutionary history of Reduviidae. Our results indicate that the polyphyletic Reduviinae fall into 11–14 separate clades. Triatominae are paraphyletic with respect to the reduviine genus Opisthacidius in the maximum likelihood analyses; this result is in contrast to prior hypotheses that found Triatominae to be monophyletic or polyphyletic and may be due to the more comprehensive taxon and character sampling in this study. The evolution of blood-feeding may thus have occurred once or twice independently among predatory assassin bugs. All prey specialists evolved from generalist ancestors, with multiple evolutionary origins of termite and ant specializations. A bark-associated life style on tree trunks is ancestral for most of the lineages of Higher Reduviidae; living on foliage has evolved at least six times independently. Reduviidae originated in the Middle Jurassic (178 Ma), but significant lineage diversification only began in the Late Cretaceous (97 Ma). The integration of molecular phylogenetics with fossil and life history data as presented in this paper provides insights into the evolutionary history of reduviids and clears the way for in-depth evolutionary hypothesis testing in one of the most speciose clades of predators.     

Reconstruction of Ancestral Gene Orders Using Probabilistic and Gene Encoding Approaches

Current tools used in the reconstruction of ancestral gene orders often fall into event-based and adjacency-based methods according to the principles they follow. Event-based methods such as GRAPPA are very accurate but with extremely high complexity, while more recent methods based on gene adjacencies such as InferCARsPro is relatively faster, but often produces an excessive number of chromosomes. This issue is mitigated by newer methods such as GapAdj, however it sacrifices a considerable portion of accuracy. We recently developed an adjacency-based method in the probabilistic framework called PMAG to infer ancestral gene orders. PMAG relies on calculating the conditional probabilities of gene adjacencies that are found in the leaf genomes using the Bayes'' theorem. It uses a novel transition model which accounts for adjacency changes along the tree branches as well as a re-rooting procedure to prevent any information loss. In this paper, we improved PMAG with a new method to assemble gene adjacencies into valid gene orders, using an exact solver for traveling salesman problem (TSP) to maximize the overall conditional probabilities. We conducted a series of simulation experiments using a wide range of configurations. The first set of experiments was to verify the effectiveness of our strategy of using the better transition model and re-rooting the tree under the targeted ancestral genome. PMAG was then thoroughly compared in terms of three measurements with its four major competitors including InferCARsPro, GapAdj, GASTS and SCJ in order to assess their performances. According to the results, PMAG demonstrates superior performance in terms of adjacency, distance and assembly accuracies, and yet achieves comparable running time, even all TSP instances were solved exactly. PMAG is available for free at http://phylo.cse.sc.edu.     

Comparative Genome-Scale Reconstruction of Gapless Metabolic Networks for Present and Ancestral Species

We introduce a novel computational approach, CoReCo, for comparative metabolic reconstruction and provide genome-scale metabolic network models for 49 important fungal species. Leveraging on the exponential growth in sequenced genome availability, our method reconstructs genome-scale gapless metabolic networks simultaneously for a large number of species by integrating sequence data in a probabilistic framework. High reconstruction accuracy is demonstrated by comparisons to the well-curated Saccharomyces cerevisiae consensus model and large-scale knock-out experiments. Our comparative approach is particularly useful in scenarios where the quality of available sequence data is lacking, and when reconstructing evolutionary distant species. Moreover, the reconstructed networks are fully carbon mapped, allowing their use in 13C flux analysis. We demonstrate the functionality and usability of the reconstructed fungal models with computational steady-state biomass production experiment, as these fungi include some of the most important production organisms in industrial biotechnology. In contrast to many existing reconstruction techniques, only minimal manual effort is required before the reconstructed models are usable in flux balance experiments. CoReCo is available at http://esaskar.github.io/CoReCo/.     

Reconstruction of Ancestral Metabolic Enzymes Reveals Molecular Mechanisms Underlying Evolutionary Innovation through Gene Duplication

Gene duplications are believed to facilitate evolutionary innovation. However, the mechanisms shaping the fate of duplicated genes remain heavily debated because the molecular processes and evolutionary forces involved are difficult to reconstruct. Here, we study a large family of fungal glucosidase genes that underwent several duplication events. We reconstruct all key ancestral enzymes and show that the very first preduplication enzyme was primarily active on maltose-like substrates, with trace activity for isomaltose-like sugars. Structural analysis and activity measurements on resurrected and present-day enzymes suggest that both activities cannot be fully optimized in a single enzyme. However, gene duplications repeatedly spawned daughter genes in which mutations optimized either isomaltase or maltase activity. Interestingly, similar shifts in enzyme activity were reached multiple times via different evolutionary routes. Together, our results provide a detailed picture of the molecular mechanisms that drove divergence of these duplicated enzymes and show that whereas the classic models of dosage, sub-, and neofunctionalization are helpful to conceptualize the implications of gene duplication, the three mechanisms co-occur and intertwine.     

Ancestral sporulation initiation

Members of the classes Bacilli and Clostridia are able to form endospores, with clostridia representing the ancestral phylogenetic line. In contrast to Bacillus subtilis, the process of sporulation initiation at the molecular level is less well understood in Clostridium acetobutylicum, the model organism of the clostridia. Especially the question of how the master regulator of sporulation, Spo0A, becomes phosphorylated, remained unsolved so far. Steiner et al. now provide compelling genetic and biochemical evidence for two different pathways of direct phosphorylation of Spo0A in C. acetobutylicum by three orphan sensor kinases. Cac0903 and Cac3319 act together, while the other pathway is only dependent on Cac0323. Abortion of sporulation initiation can be achieved by a kinase-like protein, Cac0437.     

Ancestral Processes with Selection

In this paper, we show how to construct the genealogy of a sample of genes for a large class of models with selection and mutation. Each gene corresponds to a single locus at which there is no recombination. The genealogy of the sample is embedded in a graph which we call theancestral selection graph. This graph contains all the information about the ancestry; it is the analogue of Kingman's coalescent process which arises in the case with no selection. The ancestral selection graph can be easily simulated and we outline an algorithm for simulating samples. The main goal is to analyze the ancestral selection graph and to compare it to Kingman's coalescent process. In the case of no mutation, we find that the distribution of the time to the most recent common ancestor does not depend on the selection coefficient and hence is the same as in the neutral case. When the mutation rate is positive, we give a procedure for computing the probability that two individuals in a sample are identical by descent and the Laplace transform of the time to the most recent common ancestor of a sample of two individuals; we evaluate the first two terms of their respective power series in terms of the selection coefficient. The probability of identity by descent depends on both the selection coefficient and the mutation rate and is different from the analogous expression in the neutral case. The Laplace transform does not have a linear correction term in the selection coefficient. We also provide a recursion formula that can be used to approximate the probability of a given sample by simulating backwards along the sample paths of the ancestral selection graph, a technique developed by Griffiths and Tavaré (1994).     

A Methodological Framework for the Reconstruction of Contiguous Regions of Ancestral Genomes and Its Application to Mammalian Genomes

The reconstruction of ancestral genome architectures and gene orders from homologies between extant species is a long-standing problem, considered by both cytogeneticists and bioinformaticians. A comparison of the two approaches was recently investigated and discussed in a series of papers, sometimes with diverging points of view regarding the performance of these two approaches. We describe a general methodological framework for reconstructing ancestral genome segments from conserved syntenies in extant genomes. We show that this problem, from a computational point of view, is naturally related to physical mapping of chromosomes and benefits from using combinatorial tools developed in this scope. We develop this framework into a new reconstruction method considering conserved gene clusters with similar gene content, mimicking principles used in most cytogenetic studies, although on a different kind of data. We implement and apply it to datasets of mammalian genomes. We perform intensive theoretical and experimental comparisons with other bioinformatics methods for ancestral genome segments reconstruction. We show that the method that we propose is stable and reliable: it gives convergent results using several kinds of data at different levels of resolution, and all predicted ancestral regions are well supported. The results come eventually very close to cytogenetics studies. It suggests that the comparison of methods for ancestral genome reconstruction should include the algorithmic aspects of the methods as well as the disciplinary differences in data aquisition.     

Estimating Ancestral Population Parameters

The expected numbers of different categories of polymorphic sites are derived for two related models of population history: the isolation model, in which an ancestral population splits into two descendents, and the size-change model, in which a single population undergoes an instantaneous change in size. For the isolation model, the observed numbers of shared, fixed, and exclusive polymorphic sites are used to estimate the relative sizes of the three populations, ancestral plus two descendent, as well as the time of the split. For the size-change model, the numbers of sites segregating at particular frequencies in the sample are used to estimate the relative sizes of the ancestral and descendent populations plus the time the change took place. Parameters are estimated by choosing values that most closely equate expectations with observations. Computer simulations show that current and historical population parameters can be estimated accurately. The methods are applied to DNA data from two species of Drosophila and to some human mitochondrial DNA sequences.     

Ancestral Mechanisms in Modern Environments

It is commonly assumed that the desire for a thin female physique and its pathological expression in eating disorders result from a social pressure for thinness. However, such widespread behavior may be better understood not merely as the result of arbitrary social pressure, but as an exaggerated expression of behavior that may have once been adaptive. The reproductive suppression hypothesis suggests that natural selection shaped a mechanism for adjusting female reproduction to socioecological conditions by altering the amount of body fat. In modern Western culture, social and ecological cues, which would have signaled the need for temporary postponement of reproduction in ancestral environments, may now be experienced to an unprecedented intensity and duration.     

The Historical Speciation of Mauremys Sensu Lato: Ancestral Area Reconstruction and Interspecific Gene Flow Level Assessment Provide New Insights

Mauremys sensu lato was divided into Mauremys, Chinemys, Ocadia, and Annamemys based on earlier research on morphology. Phylogenetic research on this group has been controversial because of disagreements regarding taxonomy, and the historical speciation is still poorly understood. In this study, 32 individuals of eight species that are widely distributed in Eurasia were collected. The complete mitochondrial (mt) sequences of 14 individuals of eight species were sequenced. Phylogenetic relationships, interspecific divergence times, and ancestral area reconstructions were explored using mt genome data (10,854 bp). Subsequent interspecific gene flow level assessment was performed using five unlinked polymorphic microsatellite loci. The Bayesian and maximum likelihood analyses revealed a paraphyletic relationship among four old genera (Mauremys, Annamemys, Chinemys, and Ocadia) and suggested the four old genera should be merged into the genus (Mauremys). Ancestral area reconstruction and divergence time estimation suggested Southeast Asia may be the area of origin for the common ancestral species of this genus and genetic drift may have played a decisive role in species divergence due to the isolated event of a glacial age. However, M. japonica may have been speciated due to the creation of the island of Japan. The detection of extensive gene flow suggested no vicariance occurred between Asia and Southeast Asia. Inconsistent results between gene flow assessment and phylogenetic analysis revealed the hybrid origin of M. mutica (Southeast Asian). Here ancestral area reconstruction and interspecific gene flow level assessment were first used to explore species origins and evolution of Mauremys sensu lato, which provided new insights on this genus.     

Ancestral covariance and the Bulmer effect

Summary An n-generation pedigree is set up and selection is carried out generation by generation. The influence of this procedure on the covariances in subsequent generations is assessed and, ultimately, Bulmer's general recursion formula for the reduction in genetic variance due to selection is obtained. The results are extended to assess the effect of selection of one or more characters on the genetic covariance matrix of a number of characters. The concept of ancestral regression is also used to provide a different insight into the selection process and to justify some models used in the analysis of assortative mating.     

Combinations of Ancestral Modules in Proteins

Twenty-seven protein sequence elements, six to nine amino acids long, were extracted from 15 phylogenetically diverse complete prokaryotic proteomes. The elements are present in all of these proteomes, with at least one copy each (omnipresent elements), and have presumably been conserved since the last universal common ancestor (LUCA). All these omnipresent elements are identified in crystallized protein structures as parts of highly conserved closed loops, 25–30 residues long, thus representing the closed-loop modules discovered in 2000 by Berezovsky et al. The omnipresent peptides make up seven distinct groups, of which the largest groups, Aleph and Beth, contain 18 and four elements, respectively, which are related but different, while five other groups are represented by only one element each. The LUCA modules appear with one or several copies per protein molecule in a variety of combinations depending on the functional identity of the corresponding protein. The functional involvement of individual LUCA modules is outlined on the basis of known protein annotations. Analyses of all the related sequences in a large, formatted protein sequence space suggest that many, if not all, of the 27 omnipresent elements have a common sequence origin. This sequence space network analysis may lead to elucidation of the earliest stages of protein evolution.