Ancestral Genome Reconstruction Research Articles

ContScout: sensitive detection and removal of contamination from annotated genomes

Contamination of genomes is an increasingly recognized problem affecting several downstream applications, from comparative evolutionary genomics to metagenomics. Here we introduce ContScout, a precise tool for eliminating foreign sequences from annotated genomes. It achieves high specificity and sensitivity on synthetic benchmark data even when the contaminant is a closely related species, outperforms competing tools, and can distinguish horizontal gene transfer from contamination. A screen of 844 eukaryotic genomes for contamination identified bacteria as the most common source, followed by fungi and plants. Furthermore, we show that contaminants in ancestral genome reconstructions lead to erroneous early origins of genes and inflate gene loss rates, leading to a false notion of complex ancestral genomes. Taken together, we offer here a tool for sensitive removal of foreign proteins, identify and remove contaminants from diverse eukaryotic genomes and evaluate their impact on phylogenomic analyses.

Reconstruction of Ancestral Genomes as a Key to Understanding the Early Evolution of Vertebrate Genotype

Reconstruction of Ancestral Genomes as a Key to Understanding the Early Evolution of Vertebrate Genotype

Comparative genomics of Mycoplasma feriruminatoris, a fast-growing pathogen of wild Caprinae.

Mycoplasma feriruminatoris is a fast-growing Mycoplasma species isolated from wild Caprinae and first described in 2013. M. feriruminatoris isolates have been associated with arthritis, kerato conjunctivitis, pneumonia and septicemia, but were also recovered from apparently healthy animals. To better understand what defines this species, we performed a genomic survey on 14 strains collected from free-ranging or zoo-housed animals between 1987 and 2017, mostly in Europe. The average chromosome size of the M. feriruminatoris strains was 1,040±0,024 kbp, with 24 % G+C and 852±31 CDS. The core genome and pan-genome of the M. feriruminatoris species contained 628 and 1312 protein families, respectively. The M. feriruminatoris strains displayed a relatively closed pan-genome, with many features and putative virulence factors shared with species from the M. mycoides cluster, including the MIB-MIP Ig cleavage system, a repertoire of DUF285 surface proteins and a complete biosynthetic pathway for galactan. M. feriruminatoris genomes were found to be mostly syntenic, although repertoires of mobile genetic elements, including Mycoplasma Integrative and Conjugative Elements, insertion sequences, and a single plasmid varied. Phylogenetic- and gene content analyses confirmed that M. feriruminatoris was closer to the M. mycoides cluster than to the ruminant species M. yeatsii and M. putrefaciens. Ancestral genome reconstruction showed that the emergence of the M. feriruminatoris species was associated with the gain of 17 gene families, some of which encode defence enzymes and surface proteins, and the loss of 25 others, some of which are involved in sugar transport and metabolism. This comparative study suggests that the M. mycoides cluster could be extended to include M. feriruminatoris. We also find evidence that the specific organization and structure of the DnaA boxes around the oriC of M. feriruminatoris may contribute to drive the remarkable fast growth of this minimal bacterium.

Ancestral genome reconstruction for studies of the green lineage

Ancestral genome reconstruction for studies of the green lineage

Synteny Identifies Reliable Orthologs for Phylogenomics and Comparative Genomics of the Brassicaceae.

Large genomic data sets are becoming the new normal in phylogenetic research, but the identification of true orthologous genes and the exclusion of problematic paralogs is still challenging when applying commonly used sequencing methods such as target enrichment. Here, we compared conventional ortholog detection using OrthoFinder with ortholog detection through genomic synteny in a data set of 11 representative diploid Brassicaceae whole-genome sequences spanning the entire phylogenetic space. Then, we evaluated the resulting gene sets regarding gene number, functional annotation, and gene and species tree resolution. Finally, we used the syntenic gene sets for comparative genomics and ancestral genome analysis. The use of synteny resulted in considerably more orthologs and also allowed us to reliably identify paralogs. Surprisingly, we did not detect notable differences between species trees reconstructed from syntenic orthologs when compared with other gene sets, including the Angiosperms353 set and a Brassicaceae-specific target enrichment gene set. However, the synteny data set comprised a multitude of gene functions, strongly suggesting that this method of marker selection for phylogenomics is suitable for studies that value downstream gene function analysis, gene interaction, and network studies. Finally, we present the first ancestral genome reconstruction for the Core Brassicaceae which predating the Brassicaceae lineage diversification ∼25 million years ago.

IAGS: Inferring Ancestor Genome Structure under a Wide Range of Evolutionary Scenarios.

Significant improvements in genome sequencing and assembly technology have led to increasing numbers of high-quality genomes, revealing complex evolutionary scenarios such as multiple whole-genome duplication events, which hinders ancestral genome reconstruction via the currently available computational frameworks. Here, we present the Inferring Ancestor Genome Structure (IAGS) framework, a novel block/endpoint matching optimization strategy with single-cut-or-join distance, to allow ancestral genome reconstruction under both simple (single-copy ancestor) and complex (multicopy ancestor) scenarios. We evaluated IAGS with two simulated data sets and applied it to four different real evolutionary scenarios to demonstrate its performance and general applicability. IAGS is available at https://github.com/xjtu-omics/IAGS.

Variation in Plastome Sizes Accompanied by Evolutionary History in Monogenomic Triticeae (Poaceae: Triticeae).

To investigate the pattern of chloroplast genome variation in Triticeae, we comprehensively analyzed the indels in protein-coding genes and intergenic sequence, gene loss/pseudonization, intron variation, expansion/contraction in inverted repeat regions, and the relationship between sequence characteristics and chloroplast genome size in 34 monogenomic Triticeae plants. Ancestral genome reconstruction suggests that major length variations occurred in four-stem branches of monogenomic Triticeae followed by independent changes in each genus. It was shown that the chloroplast genome sizes of monogenomic Triticeae were highly variable. The chloroplast genome of Pseudoroegneria, Dasypyrum, Lophopyrum, Thinopyrum, Eremopyrum, Agropyron, Australopyrum, and Henradia in Triticeae had evolved toward size reduction largely because of pseudogenes elimination events and length deletion fragments in intergenic. The Aegilops/Triticum complex, Taeniatherum, Secale, Crithopsis, Herteranthelium, and Hordeum in Triticeae had a larger chloroplast genome size. The large size variation in major lineages and their subclades are most likely consequences of adaptive processes since these variations were significantly correlated with divergence time and historical climatic changes. We also found that several intergenic regions, such as petN–trnC and psbE–petL containing unique genetic information, which can be used as important tools to identify the maternal relationship among Triticeae species. Our results contribute to the novel knowledge of plastid genome evolution in Triticeae.

Public good exploitation in natural bacterioplankton communities

Bacteria often interact with their environment through extracellular molecules that increase access to limiting resources. These secretions can act as public goods, creating incentives for exploiters to invade and "steal" public goods away from producers. This phenomenon has been studied extensively in vitro, but little is known about the occurrence and impact of public good exploiters in the environment. Here, we develop a genomic approach to systematically identify bacteria that can exploit public goods produced during the degradation of polysaccharides. Focusing on chitin, a highly abundant marine biopolymer, we show that public good exploiters are active in natural chitin degrading microbial communities, invading early during colonization, and potentially hindering degradation. In contrast to in vitro studies, we find that exploiters and degraders belong to distant lineages, facilitating their coexistence. Our approach opens novel avenues to use the wealth of genomic data available to infer ecological roles and interactions among microbes.

A unified ILP framework for core ancestral genome reconstruction problems.

One of the key computational problems in comparative genomics is the reconstruction of genomes of ancestral species based on genomes of extant species. Since most dramatic changes in genomic architectures are caused by genome rearrangements, this problem is often posed as minimization of the number of genome rearrangements between extant and ancestral genomes. The basic case of three given genomes is known as the genome median problem. Whole-genome duplications (WGDs) represent yet another type of dramatic evolutionary events and inspire the reconstruction of preduplicated ancestral genomes, referred to as the genome halving problem. Generalization of WGDs to whole-genome multiplication events leads to the genome aliquoting problem. In this study, we propose polynomial-size integer linear programming (ILP) formulations for the aforementioned problems. We further obtain such formulations for the restricted and conserved versions of the median and halving problems, which have been recently introduced to improve biological relevance of the solutions. Extensive evaluation of solutions to the different ILP problems demonstrates their good accuracy. Furthermore, since the ILP formulations for the conserved versions have linear size, they provide a novel practical approach to ancestral genome reconstruction, which combines the advantages of homology- and rearrangements-based methods. Code and data are available in https://github.com/AvdeevPavel/ILP-WGD-reconstructor. Supplementary data are available at Bioinformatics online.

A cubic algorithm for the generalized rank median of three genomes

BackgroundThe area of genome rearrangements has given rise to a number of interesting biological, mathematical and algorithmic problems. Among these, one of the most intractable ones has been that of finding the median of three genomes, a special case of the ancestral reconstruction problem. In this work we re-examine our recently proposed way of measuring genome rearrangement distance, namely, the rank distance between the matrix representations of the corresponding genomes, and show that the median of three genomes can be computed exactly in polynomial time O(n^omega ), where omega le 3, with respect to this distance, when the median is allowed to be an arbitrary orthogonal matrix.ResultsWe define the five fundamental subspaces depending on three input genomes, and use their properties to show that a particular action on each of these subspaces produces a median. In the process we introduce the notion of M-stable subspaces. We also show that the median found by our algorithm is always orthogonal, symmetric, and conserves any adjacencies or telomeres present in at least 2 out of 3 input genomes.ConclusionsWe test our method on both simulated and real data. We find that the majority of the realistic inputs result in genomic outputs, and for those that do not, our two heuristics perform well in terms of reconstructing a genomic matrix attaining a score close to the lower bound, while running in a reasonable amount of time. We conclude that the rank distance is not only theoretically intriguing, but also practically useful for median-finding, and potentially ancestral genome reconstruction.

Reconstruction of ancestral genome reveals chromosome evolution history for selected legume species.

Reconstruction of an ancestral genome for a set of plant species has been a challenging task because of complex histories that may include whole-genome duplications, segmental duplications, independent gene duplications or losses, diploidization and rearrangement events. Here, we describe the reconstruction a hypothetical ancestral genome for the papilionoid legumes (the largest subfamily within the third largest family in flowering plants), and evaluate the results relative to phylogenetic and chromosomal count data for this group of legumes, spanning 294 diverse papilionoid genera. To reconstruct the ancestral genomes for nine legume species with sequenced genomes, we used a maximum likelihood approach combined with a novel method for identifying informative markers for this purpose. Analyzing genomes from four species within the Phaseoleae, two in Dalbergieae, two in the 'inverted repeat loss' clade, and one in the Robinieae, we infer a common ancestral genome with nine chromosomes. The reconstructed genome structural histories are consistent with chromosomal and phylogenetic histories, but we also infer that a common ancestor with nine chromosomes was probably intermediate to an earlier state of 14 chromosomes following a whole-genome duplication that pre-dated the radiation of the papilionoid legumes, evidence for which is found in early-diverging papilionoid lineages.

On the reconstruction of the ancestral bacterial genomes in genus Mycobacterium and Brucella

BackgroundTo reconstruct the evolution history of DNA sequences, novel models of increasing complexity regarding the number of free parameters taken into account in the sequence evolution, as well as faster and more accurate algorithms, and statistical and computational methods, are needed. More particularly, as the principal forces that have led to major structural changes are genome rearrangements (such as translocations, fusions, and so on), understanding their underlying mechanisms, among other things via the ancestral genome reconstruction, are essential. In this problem, since finding the ancestral genomes that minimize the number of rearrangements in a phylogenetic tree is known to be NP-hard for three or more genomes, heuristics are commonly chosen to obtain approximations of the exact solution. The aim of this work is to show that another path is possible.ResultsVarious algorithms and software already deal with the difficult nature of the problem of reconstruction of the ancestral genome, but they do not function with precision, in particular when indels or single nucleotide polymorphisms fall into repeated sequences. In this article, and despite the theoretical NP-hardness of the ancestral reconstruction problem, we show that an exact solution can be found in practice in various cases, encompassing organelles and some bacteria. A practical example proves that an accurate reconstruction, which also allows to highlight homoplasic events, can be obtained. This is illustrated by the reconstruction of ancestral genomes of two bacterial pathogens, belonging in Mycobacterium and Brucella genera.ConclusionsBy putting together automatically reconstructed ancestral regions with handmade ones for problematic cases, we show that an accurate reconstruction of ancestors of the Brucella genus and of the Mycobacterium tuberculosis complex is possible. By doing so, we are able to investigate the evolutionary history of each pathogen by computing their common ancestors. They can be investigated extensively, by studying the gene content evolution over time, the resistance acquisition, and the impacts of mobile elements on genome plasticity.

Scaffolding of Ancient Contigs and Ancestral Reconstruction in a Phylogenetic Framework

Ancestral genome reconstruction is an important task to analyze the evolution of genomes. Recent progress in sequencing ancient DNA led to the publication of so-called paleogenomes and allows the integration of this sequencing data in genome evolution analysis. However, the de novo assembly of ancient genomes is usually fragmented due to DNA degradation over time among others. Integrated phylogenetic assembly addresses the issue of genome fragmentation in the ancient DNA assembly while aiming to improve the reconstruction of all ancient genomes in the phylogeny simultaneously. The fragmented assembly of the ancient genome can be represented as an assembly graph, indicating contradicting ordering information of contigs. In this setting, our approach is to compare the ancient data with extant finished genomes. We generalize a reconstruction approach minimizing the Single-Cut-or-Join rearrangement distance towards multifurcating trees and include edge lengths to improve the reconstruction in practice. This results in a polynomial time algorithm that includes additional ancient DNA data at one node in the tree, resulting in consistent reconstructions of ancestral genomes.

Resolution effects in reconstructing ancestral genomes

BackgroundThe reconstruction of ancestral genomes must deal with the problem of resolution, necessarily involving a trade-off between trying to identify genomic details and being overwhelmed by noise at higher resolutions.ResultsWe use the median reconstruction at the synteny block level, of the ancestral genome of the order Gentianales, based on coffee, Rhazya stricta and grape, to exemplify the effects of resolution (granularity) on comparative genomic analyses.ConclusionsWe show how decreased resolution blurs the differences between evolving genomes, with respect to rate, mutational process and other characteristics.

Ancestral Genome Reconstruction on Whole Genome Level.

Comparative genomics, evolutionary biology, and cancer researches require tools to elucidate the evolutionary trajectories and reconstruct the ancestral genomes. Various methods have been developed to infer the genome content and gene ordering of ancestral genomes by using such genomic structural variants. There are mainly two kinds of computational approaches in the ancestral genome reconstruction study. Distance/event-based approaches employ genome evolutionary models and reconstruct the ancestral genomes that minimize the total distance or events over the edges of the given phylogeny. The homology/adjacency-based approaches search for the conserved gene adjacencies and genome structures, and assemble these regions into ancestral genomes along the internal node of the given phylogeny. We review the principles and algorithms of these approaches that can reconstruct the ancestral genomes on the whole genome level. We talk about their advantages and limitations of these approaches in dealing with various genome datasets, evolutionary events, and reconstruction problems. We also talk about the improvements and developments of these approaches in the subsequent researches. We select four most famous and powerful approaches from both distance/event-based and homology/adjacency-based categories to analyze and compare their performances in dealing with different kinds of datasets and evolutionary events. Based on our experiment, GASTS has the best performance in solving the problems with equal genome contents that only have genome rearrangement events. PMAG++ achieves the best performance in solving the problems with unequal genome contents that have all possible complicated evolutionary events.

Genomes as documents of evolutionary history: a probabilistic macrosynteny model for the reconstruction of ancestral genomes.

MotivationIt has been argued that whole-genome duplication (WGD) exerted a profound influence on the course of evolution. For the purpose of fully understanding the impact of WGD, several formal algorithms have been developed for reconstructing pre-WGD gene order in yeast and plant. However, to the best of our knowledge, those algorithms have never been successfully applied to WGD events in teleost and vertebrate, impeded by extensive gene shuffling and gene losses.ResultsHere, we present a probabilistic model of macrosynteny (i.e. conserved linkage or chromosome-scale distribution of orthologs), develop a variational Bayes algorithm for inferring the structure of pre-WGD genomes, and study estimation accuracy by simulation. Then, by applying the method to the teleost WGD, we demonstrate effectiveness of the algorithm in a situation where gene-order reconstruction algorithms perform relatively poorly due to a high rate of rearrangement and extensive gene losses. Our high-resolution reconstruction reveals previously overlooked small-scale rearrangements, necessitating a revision to previous views on genome structure evolution in teleost and vertebrate.ConclusionsWe have reconstructed the structure of a pre-WGD genome by employing a variational Bayes approach that was originally developed for inferring topics from millions of text documents. Interestingly, comparison of the macrosynteny and topic model algorithms suggests that macrosynteny can be regarded as documents on ancestral genome structure. From this perspective, the present study would seem to provide a textbook example of the prevalent metaphor that genomes are documents of evolutionary history.Availability and implementationThe analysis data are available for download at http://www.gen.tcd.ie/molevol/supp_data/MacrosyntenyTGD.zip, and the software written in Java is available upon request.Supplementary information Supplementary data are available at Bioinformatics online.

Prediction of human miRNA target genes using computationally reconstructed ancestral mammalian sequences.

MicroRNAs (miRNA) are short single-stranded RNA molecules derived from hairpin-forming precursors that play a crucial role as post-transcriptional regulators in eukaryotes and viruses. In the past years, many microRNA target genes (MTGs) have been identified experimentally. However, because of the high costs of experimental approaches, target genes databases remain incomplete. Although several target prediction programs have been developed in the recent years to identify MTGs in silico, their specificity and sensitivity remain low. Here, we propose a new approach called MirAncesTar, which uses ancestral genome reconstruction to boost the accuracy of existing MTGs prediction tools for human miRNAs. For each miRNA and each putative human target UTR, our algorithm makes uses of existing prediction tools to identify putative target sites in the human UTR, as well as in its mammalian orthologs and inferred ancestral sequences. It then evaluates evidence in support of selective pressure to maintain target site counts (rather than sequences), accounting for the possibility of target site turnover. It finally integrates this measure with several simpler ones using a logistic regression predictor. MirAncesTar improves the accuracy of existing MTG predictors by 26% to 157%. Source code and prediction results for human miRNAs, as well as supporting evolutionary data are available at http://cs.mcgill.ca/∼blanchem/mirancestar.

Comparative genomics meets topology: a novel view on genome median and halving problems.

BackgroundGenome median and genome halving are combinatorial optimization problems that aim at reconstruction of ancestral genomes by minimizing the number of evolutionary events between them and genomes of the extant species. While these problems have been widely studied in past decades, their solutions are often either not efficient or not biologically adequate. These shortcomings have been recently addressed by restricting the problems solution space.ResultsWe show that the restricted variants of genome median and halving problems are, in fact, closely related. We demonstrate that these problems have a neat topological interpretation in terms of embedded graphs and polygon gluings. We illustrate how such interpretation can lead to solutions to these problems in particular cases.ConclusionsThis study provides an unexpected link between comparative genomics and topology, and demonstrates advantages of solving genome median and halving problems within the topological framework.

Fast ancestral gene order reconstruction of genomes with unequal gene content.

BackgroundDuring evolution, genomes are modified by large scale structural events, such as rearrangements, deletions or insertions of large blocks of DNA. Of particular interest, in order to better understand how this type of genomic evolution happens, is the reconstruction of ancestral genomes, given a phylogenetic tree with extant genomes at its leaves. One way of solving this problem is to assume a rearrangement model, such as Double Cut and Join (DCJ), and find a set of ancestral genomes that minimizes the number of events on the input tree. Since this problem is NP-hard for most rearrangement models, exact solutions are practical only for small instances, and heuristics have to be used for larger datasets. This type of approach can be called event-based. Another common approach is based on finding conserved structures between the input genomes, such as adjacencies between genes, possibly also assigning weights that indicate a measure of confidence or probability that this particular structure is present on each ancestral genome, and then finding a set of non conflicting adjacencies that optimize some given function, usually trying to maximize total weight and minimizing character changes in the tree. We call this type of methods homology-based.ResultsIn previous work, we proposed an ancestral reconstruction method that combines homology- and event-based ideas, using the concept of intermediate genomes, that arise in DCJ rearrangement scenarios. This method showed better rate of correctly reconstructed adjacencies than other methods, while also being faster, since the use of intermediate genomes greatly reduces the search space. Here, we generalize the intermediate genome concept to genomes with unequal gene content, extending our method to account for gene insertions and deletions of any length. In many of the simulated datasets, our proposed method had better results than MLGO and MGRA, two state-of-the-art algorithms for ancestral reconstruction with unequal gene content, while running much faster, making it more scalable to larger datasets.ConclusionStuding ancestral reconstruction problems under a new light, using the concept of intermediate genomes, allows the design of very fast algorithms by greatly reducing the solution search space, while also giving very good results. The algorithms introduced in this paper were implemented in an open-source software called RINGO (ancestral Reconstruction with INtermediate GenOmes), available at https://github.com/pedrofeijao/RINGO.

Ancestral genome reconstruction identifies the evolutionary basis for trait acquisition in polyphosphate accumulating bacteria.

The evolution of complex traits is hypothesized to occur incrementally. Identifying the transitions that lead to extant complex traits may provide a better understanding of the genetic nature of the observed phenotype. A keystone functional group in wastewater treatment processes are polyphosphate accumulating organisms (PAOs), however the evolution of the PAO phenotype has yet to be explicitly investigated and the specific metabolic traits that discriminate non-PAO from PAO are currently unknown. Here we perform the first comprehensive investigation on the evolution of the PAO phenotype using the model uncultured organism Candidatus Accumulibacter phosphatis (Accumulibacter) through ancestral genome reconstruction, identification of horizontal gene transfer, and a kinetic/stoichiometric characterization of Accumulibacter Clade IIA. The analysis of Accumulibacter's last common ancestor identified 135 laterally derived genes, including genes involved in glycogen, polyhydroxyalkanoate, pyruvate and NADH/NADPH metabolisms, as well as inorganic ion transport and regulatory mechanisms. In contrast, pathways such as the TCA cycle and polyphosphate metabolism displayed minimal horizontal gene transfer. We show that the transition from non-PAO to PAO coincided with horizontal gene transfer within Accumulibacter's core metabolism; likely alleviating key kinetic and stoichiometric bottlenecks, such as anaerobically linking glycogen degradation to polyhydroxyalkanoate synthesis. These results demonstrate the utility of investigating the derived genome of a lineage to identify key transitions leading to an extant complex phenotype.