基因水平转移的评判方法和转移方式研究进展

基因水平转移是不同物种之间或细胞器间基因的交流。基因水平转移现象在原核生物中普遍存在, 在真核生物中近年来也发现了众多例证, 说明水平转移是生物界的普遍现象。文章着重对基因水平转移的概念、评判基因水平转移的标准, 水平转移的特点和转移方式, 以及基因水平转移对基因组进化的作用等方面的研究进展进行了综述。在已有的基因水平转移研究中进化树分析法、碱基组成分析法、选择压力分析法、内含子分析法、特殊序列分析法和核苷酸组成偏向性分析法等几种是常用的方法; 转座序列是生物中最易于发生水平转移的基因类型;原核生物基因水平转移的主要方式有转化、接合和转导, 真核生物中水平转移发生方式尚不清楚。基因水平转移在基因、基因组和生物进化中有着其独特的作用。     

Simultaneous identification of duplications and lateral gene transfers

The incongruency between a gene tree and a corresponding species tree can be attributed to evolutionary events such as gene duplication and gene loss. This paper describes a combinatorial model where so-called DTL-scenarios are used to explain the differences between a gene tree and a corresponding species tree taking into account gene duplications, gene losses, and lateral gene transfers (also known as horizontal gene transfers). The reasonable biological constraint that a lateral gene transfer may only occur between contemporary species leads to the notion of acyclic DTL-scenarios. Parsimony methods are introduced by defining appropriate optimization problems. We show that finding most parsimonious acyclic DTL-scenarios is NP-hard. However, by dropping the condition of acyclicity, the problem becomes tractable, and we provide a dynamic programming algorithm as well as a fixed-parameter tractable algorithm for finding most parsimonious DTL-scenarios.     

A model of horizontal gene transfer and the bacterial phylogeny problem

How much horizontal gene transfer (HGT) between species influences bacterial phylogenomics is a controversial issue. This debate, however, lacks any quantitative assessment of the impact of HGT on phylogenies and of the ability of tree-building methods to cope with such events. I introduce a Markov model of genome evolution with HGT, accounting for the constraints on time -- an HGT event can only occur between concomitantly living species. This model is used to simulate multigene sequence data sets with or without HGT. The consequences of HGT on phylogenomic inference are analyzed and compared to other well-known phylogenetic artefacts. It is found that supertree methods are quite robust to HGT, keeping high levels of performance even when gene trees are largely incongruent with each other. Gene tree incongruence per se is not indicative of HGT. HGT, however, removes the (otherwise observed) positive relationship between sequence length and gene tree congruence to the estimated species tree. Surprisingly, when applied to a bacterial and a eukaryotic multigene data set, this criterion rejects the HGT hypothesis for the former, but not the latter data set.     

Species trees from gene trees: reconstructing Bayesian posterior distributions of a species phylogeny using estimated gene tree distributions

The desire to infer the evolutionary history of a group of species should be more viable now that a considerable amount of multilocus molecular data is available. However, the current molecular phylogenetic paradigm still reconstructs gene trees to represent the species tree. Further, commonly used methods of combining data, such as the concatenation method, are known to be inconsistent in some circumstances. In this paper, we propose a Bayesian hierarchical model to estimate the phylogeny of a group of species using multiple estimated gene tree distributions, such as those that arise in a Bayesian analysis of DNA sequence data. Our model employs substitution models used in traditional phylogenetics but also uses coalescent theory to explain genealogical signals from species trees to gene trees and from gene trees to sequence data, thereby forming a complete stochastic model to estimate gene trees, species trees, ancestral population sizes, and species divergence times simultaneously. Our model is founded on the assumption that gene trees, even of unlinked loci, are correlated due to being derived from a single species tree and therefore should be estimated jointly. We apply the method to two multilocus data sets of DNA sequences. The estimates of the species tree topology and divergence times appear to be robust to the prior of the population size, whereas the estimates of effective population sizes are sensitive to the prior used in the analysis. These analyses also suggest that the model is superior to the concatenation method in fitting these data sets and thus provides a more realistic assessment of the variability in the distribution of the species tree that may have produced the molecular information at hand. Future improvements of our model and algorithm should include consideration of other factors that can cause discordance of gene trees and species trees, such as horizontal transfer or gene duplication.     

Evolution of mercuric reductase (merA) gene: a case of horizontal gene transfer

In the present study the role of horizontal gene transfer events in providing the mercury resistance is depicted. merA is key gene in mer operon and has been used for this study. Phylogenetic analysis of aligned merA sequences shows broad similarities to the established 16S rRNA phylogeny. But there is no separation of bacterial merA from archael merA which suggests that merA gene in both these groups share considerable sequence homology. However, inconsistencies between merA and 16S rRNA gene phylogenetic trees are apparent for some taxa. These discrepancies in the phylogenetic trees for merA gene and 16S rRNA gene have lead to the suggestion that horizontal gene transfer (HGT) is a major contributor for its evolution. The close association among members of different groups in merA gene tree, as supported by high bootstrap values, deviations in GC content and codon usage pattern indicate the possibility that horizontal gene transfer events might have taken place during the evolution of this gene.     

Dealing with incongruence in phylogenomic analyses

Incongruence between gene trees is the main challenge faced by phylogeneticists in the genomic era. Incongruence can occur for artefactual reasons, when we fail to recover the correct gene trees, or for biological reasons, when true gene trees are actually distinct from each other, and from the species tree. Horizontal gene transfers (HGTs) between genomes are an important process of bacterial evolution resulting in a substantial amount of phylogenetic conflicts between gene trees. We argue that the (bacterial) species tree is still a meaningful scientific concept even in the case of HGTs, and that reconstructing it is still a valid goal. We tentatively assess the amount of phylogenetic incongruence caused by HGTs in bacteria by comparing bacterial datasets to a metazoan dataset in which transfers are presumably very scarce or absent.We review existing phylogenomic methods and their ability to return to the user, both the vertical (speciation/extinction history) and horizontal (gene transfers) phylogenetic signals.     

From gene trees to species trees II: species tree inference by minimizing deep coalescence events

When gene copies are sampled from various species, the resulting gene tree might disagree with the containing species tree. The primary causes of gene tree and species tree discord include incomplete lineage sorting, horizontal gene transfer, and gene duplication and loss. Each of these events yields a different parsimony criterion for inferring the (containing) species tree from gene trees. With incomplete lineage sorting, species tree inference is to find the tree minimizing extra gene lineages that had to coexist along species lineages; with gene duplication, it becomes to find the tree minimizing gene duplications and/or losses. In this paper, we present the following results: 1) The deep coalescence cost is equal to the number of gene losses minus two times the gene duplication cost in the reconciliation of a uniquely leaf labeled gene tree and a species tree. The deep coalescence cost can be computed in linear time for any arbitrary gene tree and species tree. 2) The deep coalescence cost is always not less than the gene duplication cost in the reconciliation of an arbitrary gene tree and a species tree. 3) Species tree inference by minimizing deep coalescence events is NP-hard.     

The Consistent Phylogenetic Signal in Genome Trees Revealed by Reducing the Impact of Noise

Phylogenetic trees based on gene repertoires are remarkably similar to the current consensus of life history. Yet it has been argued that shared gene content is unreliable for phylogenetic reconstruction because of convergence in gene content due to horizontal gene transfer and parallel gene loss. Here we test this argument, by filtering out as noise those orthologous groups that have an inconsistent phylogenetic distribution, using two independent methods. The resulting phylogenies do indeed contain small but significant improvements. More importantly, we find that the majority of orthologous groups contain some phylogenetic signal and that the resulting phylogeny is the only detectable signal present in the gene distribution across genomes. Horizontal gene transfer or parallel gene loss does not cause systematic biases in the gene content tree.     

SHOT: a web server for the construction of genome phylogenies

With the increasing availability of genome sequences, new methods are being proposed that exploit information from complete genomes to classify species in a phylogeny. Here we present SHOT, a web server for the classification of genomes on the basis of shared gene content or the conservation of gene order that reflects the dominant, phylogenetic signal in these genomic properties. In general, the genome trees are consistent with classical gene-based phylogenies, although some interesting exceptions indicate massive horizontal gene transfer. SHOT is a useful tool for analysing the tree of life from a genomic point of view. It is available at http://www.Bork.EMBL-Heidelberg.de/SHOT.     

Reconstructing the evolution of genes along the species tree

A model and algorithm are proposed to infer the evolution of a gene family described by the corresponding gene tree, with respect to the species evolution described by the corresponding species tree. The model describes the evolution using the new concept of a nested tree. The algorithm performance is illustrated by the example of several orthologous protein groups. The considered evolutionary events are speciation, gene duplication and loss, and horizontal gene transfer retaining the original gene copy. The transfer event with the loss of the original gene copy is considered as a combination of gene transfer and loss. The model maps each evolutionary event onto the species phylogeny.     

Evolution of mercuric reductase (<Emphasis Type="Italic">merA</Emphasis>) gene: A case of horizontal gene transfer

In the present study the role of horizontal gene transfer events in providing the mercury resistance is depicted. merA gene is key gene in mer operon and has been used for this swtudy. Phylogenetic analysis of aligned merA gene sequences shows broad similarities to the established 16S rRNA gene phylogeny. But there is no separation of bacterial merA gene from archael merA gene which suggests that merA gene in both these groups share considerable sequence homology. However, inconsistencies between merA gene and 16S rRNA gene phylogenetic trees are apparent for some taxa. These discrepancies in the phylogenetic trees for merA gene and 16S rRNA gene have lead to the suggestion that horizontal gene transfer (HGT) is a major contributor for its evolution. The close association among members of different groups in merA gene tree, as supported by high bootstrap values, deviations in GC content and codon usage pattern indicate the possibility that horizontal gene transfer events might have taken place during the evolution of this gene.     

Functional divergence and horizontal transfer of type IV secretion systems

The type IV secretion system (TFSSs) is a multifunctional family of translocation pathways that mediate the transfer of DNA among bacteria and deliver DNA and proteins to eukaryotic cells during bacterial infections. Horizontal transmission has dominated the evolution of the TFSS, as demonstrated here by a lack of congruence between the tree topology inferred from components of the TFSS and the presumed bacterial species divergence pattern. A parsimony analysis suggests that conjugation represents the ancestral state and that the divergence from conjugation to secretion of effector molecules has occurred independently at multiple sites in the tree. The result shows that the nodes at which functional shifts have occurred coincide with those of horizontal gene transfers among distantly related bacteria. We suggest that it is the transfer between species that paved the way for the divergence of the TFSSs and discuss the general role of horizontal gene transfers for the evolution of novel gene functions.     

Application of phylogenetic networks in evolutionary studies

The evolutionary history of a set of taxa is usually represented by a phylogenetic tree, and this model has greatly facilitated the discussion and testing of hypotheses. However, it is well known that more complex evolutionary scenarios are poorly described by such models. Further, even when evolution proceeds in a tree-like manner, analysis of the data may not be best served by using methods that enforce a tree structure but rather by a richer visualization of the data to evaluate its properties, at least as an essential first step. Thus, phylogenetic networks should be employed when reticulate events such as hybridization, horizontal gene transfer, recombination, or gene duplication and loss are believed to be involved, and, even in the absence of such events, phylogenetic networks have a useful role to play. This article reviews the terminology used for phylogenetic networks and covers both split networks and reticulate networks, how they are defined, and how they can be interpreted. Additionally, the article outlines the beginnings of a comprehensive statistical framework for applying split network methods. We show how split networks can represent confidence sets of trees and introduce a conservative statistical test for whether the conflicting signal in a network is treelike. Finally, this article describes a new program, SplitsTree4, an interactive and comprehensive tool for inferring different types of phylogenetic networks from sequences, distances, and trees.     

Methods of horizontal gene transfer determination using phylogenetic data

A new approach for comparative analysis of multiple trees reconstructed for representative protein families is proposed. This approach is based on the hypothesis of gene duplication, gene loss and horizontal gene transfer and makes use of stochastic methods and optimization. We present a species tree of 40 prokaryotic organisms obtained by our algorithm on the basis of 132 clusters of orthologous groups of proteins (COGs) from the GenBank of the National Center for Biotechnology Information (USA). We also present a computer technology intended to determine horizontally transferred genes. Some application results of the technology, based on comparative analysis of protein and species trees, are given.     

The probability of a gene tree topology within a phylogenetic network with applications to hybridization detection

Gene tree topologies have proven a powerful data source for various tasks, including species tree inference and species delimitation. Consequently, methods for computing probabilities of gene trees within species trees have been developed and widely used in probabilistic inference frameworks. All these methods assume an underlying multispecies coalescent model. However, when reticulate evolutionary events such as hybridization occur, these methods are inadequate, as they do not account for such events. Methods that account for both hybridization and deep coalescence in computing the probability of a gene tree topology currently exist for very limited cases. However, no such methods exist for general cases, owing primarily to the fact that it is currently unknown how to compute the probability of a gene tree topology within the branches of a phylogenetic network. Here we present a novel method for computing the probability of gene tree topologies on phylogenetic networks and demonstrate its application to the inference of hybridization in the presence of incomplete lineage sorting. We reanalyze a Saccharomyces species data set for which multiple analyses had converged on a species tree candidate. Using our method, though, we show that an evolutionary hypothesis involving hybridization in this group has better support than one of strict divergence. A similar reanalysis on a group of three Drosophila species shows that the data is consistent with hybridization. Further, using extensive simulation studies, we demonstrate the power of gene tree topologies at obtaining accurate estimates of branch lengths and hybridization probabilities of a given phylogenetic network. Finally, we discuss identifiability issues with detecting hybridization, particularly in cases that involve extinction or incomplete sampling of taxa.     

GeneRax: A Tool for Species-Tree-Aware Maximum Likelihood-Based Gene Family Tree Inference under Gene Duplication,Transfer, and Loss

Inferring phylogenetic trees for individual homologous gene families is difficult because alignments are often too short, and thus contain insufficient signal, while substitution models inevitably fail to capture the complexity of the evolutionary processes. To overcome these challenges, species-tree-aware methods also leverage information from a putative species tree. However, only few methods are available that implement a full likelihood framework or account for horizontal gene transfers. Furthermore, these methods often require expensive data preprocessing (e.g., computing bootstrap trees) and rely on approximations and heuristics that limit the degree of tree space exploration. Here, we present GeneRax, the first maximum likelihood species-tree-aware phylogenetic inference software. It simultaneously accounts for substitutions at the sequence level as well as gene level events, such as duplication, transfer, and loss relying on established maximum likelihood optimization algorithms. GeneRax can infer rooted phylogenetic trees for multiple gene families, directly from the per-gene sequence alignments and a rooted, yet undated, species tree. We show that compared with competing tools, on simulated data GeneRax infers trees that are the closest to the true tree in 90% of the simulations in terms of relative Robinson–Foulds distance. On empirical data sets, GeneRax is the fastest among all tested methods when starting from aligned sequences, and it infers trees with the highest likelihood score, based on our model. GeneRax completed tree inferences and reconciliations for 1,099 Cyanobacteria families in 8 min on 512 CPU cores. Thus, its parallelization scheme enables large-scale analyses. GeneRax is available under GNU GPL at https://github.com/BenoitMorel/GeneRax (last accessed June 17, 2020).       

iGTP: A software package for large-scale gene tree parsimony analysis

Background  

The ever-increasing wealth of genomic sequence information provides an unprecedented opportunity for large-scale phylogenetic analysis. However, species phylogeny inference is obfuscated by incongruence among gene trees due to evolutionary events such as gene duplication and loss, incomplete lineage sorting (deep coalescence), and horizontal gene transfer. Gene tree parsimony (GTP) addresses this issue by seeking a species tree that requires the minimum number of evolutionary events to reconcile a given set of incongruent gene trees. Despite its promise, the use of gene tree parsimony has been limited by the fact that existing software is either not fast enough to tackle large data sets or is restricted in the range of evolutionary events it can handle.     

How well do multispecies coalescent methods perform with mitochondrial genomic data? A case study of butterflies and moths (Insecta: Lepidoptera)

Despite the broad adoption of multispecies coalescent (MSC) methods for nuclear phylogenomics, they have yet to be applied to mitochondrial (mt) genomic data. As the potential sources of phylogenomic bias that MSC methods can address, such as incomplete lineage sorting, horizontal gene transfer and gene tree heterogeneity, have been found in mt genomic data, these approaches may improve the accuracy of phylogenetic inference with these data. In the present study, we examined the behaviour of MSC methods in reconstructing the phylogeny of Lepidoptera (butterflies and moths), a group for which mt genomic data are known to have strong resolving power. Traditional concatenation methods of analysing mt genomes for Lepidoptera infer topologies highly congruent with those generated from independent nuclear datasets. Individual mt gene trees performed poorly in recovering consensus relationships at deep levels (i.e. superfamily monophyly and inter-relationships) and only moderately well for shallow relationships (i.e. within Papilionoidea). In contrast, MSC analyses with ASTRAL performed strongly with almost complete concordance to both concatenated mt genome analyses and independent nuclear analyses at both deep and shallow phylogenetic scales. Outgroup choice had a limited impact on tree accuracy, with even phylogenetically distant outgroups still resulting in topologies highly congruent with results from nuclear datasets, although MSC analyses appeared to be marginally more affected by outgroup choice than concatenation analyses. In general, discordance between concatenation and MSC analyses was found at nodes whose resolution varied between previous nuclear phylogenomic studies. The sensitivity of individual relationships to analysis with MSC vs concatenation can thus be used to test the robustness of phylogenetic hypotheses. For insect phylogenetics, MSC is a reliable inference method for mt genomic data and is thus a useful complement to the already widely used concatenation approaches.     

Genetic relationships among 527 Gram-negative bacterial plasmids

Plasmids are mosaic in composition with a maintenance "backbone" as well as "accessory" genes obtained via horizontal gene transfer. This horizontal gene transfer complicates the study of their genetic relationships. We describe a method for relating a large number of Gram-negative (GN) bacterial plasmids based on their genetic sequences. Complete coding gene sequences of 527 GN bacterial plasmids were obtained from NCBI. Initial classification of their genetic relationships was accomplished using a computational approach analogous to hybridization of "mixed-genome microarrays." Because of this similarity, the phrase "virtual hybridization" is used to describe this approach. Protein sequences generated from the gene sequences were randomly chosen to serve as "probes" for the virtual arrays, and virtual hybridization for each GN plasmid was achieved using BLASTp. Each resulting intensity matrix was used to generate a distance matrix from which an initial tree was constructed. Relationships were refined for several clusters by identifying conserved proteins within a cluster. Multiple-sequence alignment was applied to the concatenated conserved proteins, and maximum likelihood was used to generate relationships from the results of the alignment. While it is not possible to prove that the genetic relationships among the 527 GN bacterial plasmids obtained in this study are correct, replication of identical results produced in a separate study for a small group of IncA/C plasmids provides evidence that the approach used can correctly predict genetic relationships. In addition, results obtained for clusters of Borrelia plasmids are consistent with the expected exclusivity for plasmids from this genus. Finally, the 527-plasmid tree was used to study the distribution of four common antibiotic resistance genes.     

A hybrid micro-macroevolutionary approach to gene tree reconstruction.

Gene family evolution is determined by microevolutionary processes (e.g., point mutations) and macroevolutionary processes (e.g., gene duplication and loss), yet macroevolutionary considerations are rarely incorporated into gene phylogeny reconstruction methods. We present a dynamic program to find the most parsimonious gene family tree with respect to a macroevolutionary optimization criterion, the weighted sum of the number of gene duplications and losses. The existence of a polynomial delay algorithm for duplication/loss phylogeny reconstruction stands in contrast to most formulations of phylogeny reconstruction, which are NP-complete. We next extend this result to obtain a two-phase method for gene tree reconstruction that takes both micro- and macroevolution into account. In the first phase, a gene tree is constructed from sequence data, using any of the previously known algorithms for gene phylogeny construction. In the second phase, the tree is refined by rearranging regions of the tree that do not have strong support in the sequence data to minimize the duplication/lost cost. Components of the tree with strong support are left intact. This hybrid approach incorporates both micro- and macroevolutionary considerations, yet its computational requirements are modest in practice because the two-phase approach constrains the search space. Our hybrid algorithm can also be used to resolve nonbinary nodes in a multifurcating gene tree. We have implemented these algorithms in a software tool, NOTUNG 2.0, that can be used as a unified framework for gene tree reconstruction or as an exploratory analysis tool that can be applied post hoc to any rooted tree with bootstrap values. The NOTUNG 2.0 graphical user interface can be used to visualize alternate duplication/loss histories, root trees according to duplication and loss parsimony, manipulate and annotate gene trees, and estimate gene duplication times. It also offers a command line option that enables high-throughput analysis of a large number of trees.