The History of Chromosomal Instability in Genome-Doubled Tumors.

Tumors frequently display high chromosomal instability and contain multiple copies of genomic regions. Here, we describe Gain Route Identification and Timing In Cancer (GRITIC), a generic method for timing genomic gains leading to complex copy number states, using single-sample bulk whole-genome sequencing data. By applying GRITIC to 6,091 tumors, we found that non-parsimonious evolution is frequent in the formation of complex copy number states in genome-doubled tumors.

NestedBD: Bayesian inference of phylogenetic trees from single-cell copy number profiles under a birth-death model.

Copy number aberrations (CNAs) are ubiquitous in many types of cancer. Inferring CNAs from cancer genomic data could help shed light on the initiation, progression, and potential treatment of cancer. While such data have traditionally been available via "bulk sequencing," the more recently introduced techniques for single-cell DNA sequencing (scDNAseq) provide the type of data that makes CNA inference possible at the single-cell resolution.

Accurate integration of single-cell DNA and RNA for analyzing intratumor heterogeneity using MaCroDNA.

Cancers develop and progress as mutations accumulate, and with the advent of single-cell DNA and RNA sequencing, researchers can observe these mutations and their transcriptomic effects and predict proteomic changes with remarkable temporal and spatial precision. However, to connect genomic mutations with their transcriptomic and proteomic consequences, cells with either only DNA data or only RNA data must be mapped to a common domain. For this purpose, we present MaCroDNA, a method that uses maximum weighted bipartite matching of per-gene read counts from single-cell DNA and RNA-seq data.

"Correcting" Gene Trees to be More Like Species Trees Frequently Increases Topological Error.

The evolutionary histories of individual loci in a genome can be estimated independently, but this approach is error-prone due to the limited amount of sequence data available for each gene, which has led to the development of a diverse array of gene tree error correction methods which reduce the distance to the species tree. We investigate the performance of two representatives of these methods: TRACTION and TreeFix. We found that gene tree error correction frequently increases the level of error in gene tree topologies by "correcting" them to be closer to the species tree, even when the true gene and species trees are discordant.

Comparing inference under the multispecies coalescent with and without recombination.

Accurate inference of population parameters plays a pivotal role in unravelling evolutionary histories. While recombination has been universally accepted as a fundamental process in the evolution of sexually reproducing organisms, it remains challenging to model it exactly. Thus, existing coalescent-based approaches make different assumptions or approximations to facilitate phylogenetic inference, which can potentially bring about biases in estimates of evolutionary parameters when recombination is present.

Annotation-free delineation of prokaryotic homology groups.

Phylogenomic studies of prokaryotic taxa often assume conserved marker genes are homologous across their length. However, processes such as horizontal gene transfer or gene duplication and loss may disrupt this homology by recombining only parts of genes, causing gene fission or fusion. We show using simulation that it is necessary to delineate homology groups in a set of bacterial genomes without relying on gene annotations to define the boundaries of homologous regions.

Maximum Parsimony Inference of Phylogenetic Networks in the Presence of Polyploid Complexes.

Phylogenetic networks provide a powerful framework for modeling and analyzing reticulate evolutionary histories. While polyploidy has been shown to be prevalent not only in plants but also in other groups of eukaryotic species, most work done thus far on phylogenetic network inference assumes diploid hybridization. These inference methods have been applied, with varying degrees of success, to data sets with polyploid species, even though polyploidy violates the mathematical assumptions underlying these methods.

Variational inference using approximate likelihood under the coalescent with recombination.

Coalescent methods are proven and powerful tools for population genetics, phylogenetics, epidemiology, and other fields. A promising avenue for the analysis of large genomic alignments, which are increasingly common, is coalescent hidden Markov model (coalHMM) methods, but these methods have lacked general usability and flexibility. We introduce a novel method for automatically learning a coalHMM and inferring the posterior distributions of evolutionary parameters using black-box variational inference, with the transition rates between local genealogies derived empirically by simulation.

Phylogenomic assessment of the role of hybridization and introgression in trait evolution.

Trait evolution among a set of species-a central theme in evolutionary biology-has long been understood and analyzed with respect to a species tree. However, the field of phylogenomics, which has been propelled by advances in sequencing technologies, has ushered in the era of species/gene tree incongruence and, consequently, a more nuanced understanding of trait evolution. For a trait whose states are incongruent with the branching patterns in the species tree, the same state could have arisen independently in different species (homoplasy) or followed the branching patterns of gene trees, incongruent with the species tree (hemiplasy).

Novel Integrative Modeling of Molecules and Morphology across Evolutionary Timescales.

Evolutionary models account for either population- or species-level processes but usually not both. We introduce a new model, the FBD-MSC, which makes it possible for the first time to integrate both the genealogical and fossilization phenomena, by means of the multispecies coalescent (MSC) and the fossilized birth-death (FBD) processes. Using this model, we reconstruct the phylogeny representing all extant and many fossil Caninae, recovering both the relative and absolute time of speciation events.

Practical Speedup of Bayesian Inference of Species Phylogenies by Restricting the Space of Gene Trees.

Species tree inference from multilocus data has emerged as a powerful paradigm in the postgenomic era, both in terms of the accuracy of the species tree it produces as well as in terms of elucidating the processes that shaped the evolutionary history. Bayesian methods for species tree inference are desirable in this area as they have been shown not only to yield accurate estimates, but also to naturally provide measures of confidence in those estimates. However, the heavy computational requirements of Bayesian inference have limited the applicability of such methods to very small data sets.

Rosette core fungal resistance in Arabidopsis thaliana.

Unlike rosette leaves, the mature Arabidopsis rosette core can display full resistance to Botrytis cinerea revealing the importance for spatial and developmental aspects of plant fungal resistance. Arabidopsis thaliana is a model host to investigate plant defense against fungi. However, many of the reports investigating Arabidopsis fungal defense against the necrotrophic fungus, Botrytis cinerea, utilize rosette leaves as host tissue.

A divide-and-conquer method for scalable phylogenetic network inference from multilocus data.

Motivation: Reticulate evolutionary histories, such as those arising in the presence of hybridization, are best modeled as phylogenetic networks. Recently developed methods allow for statistical inference of phylogenetic networks while also accounting for other processes, such as incomplete lineage sorting. However, these methods can only handle a small number of loci from a handful of genomes.

CEP-CEPR1 signalling inhibits the sucrose-dependent enhancement of lateral root growth.

Lateral root (LR) proliferation is a major determinant of soil nutrient uptake. How resource allocation controls the extent of LR growth remains unresolved. We used genetic, physiological, transcriptomic, and grafting approaches to define a role for C-TERMINALLY ENCODED PEPTIDE RECEPTOR 1 (CEPR1) in controlling sucrose-dependent LR growth.

BEAST 2.5: An advanced software platform for Bayesian evolutionary analysis.

Elaboration of Bayesian phylogenetic inference methods has continued at pace in recent years with major new advances in nearly all aspects of the joint modelling of evolutionary data. It is increasingly appreciated that some evolutionary questions can only be adequately answered by combining evidence from multiple independent sources of data, including genome sequences, sampling dates, phenotypic data, radiocarbon dates, fossil occurrences, and biogeographic range information among others. Including all relevant data into a single joint model is very challenging both conceptually and computationally.

Bayesian Inference of Species Networks from Multilocus Sequence Data.

Reticulate species evolution, such as hybridization or introgression, is relatively common in nature. In the presence of reticulation, species relationships can be captured by a rooted phylogenetic network, and orthologous gene evolution can be modeled as bifurcating gene trees embedded in the species network. We present a Bayesian approach to jointly infer species networks and gene trees from multilocus sequence data.

Validation and description of two new north-western Australian Rainbow skinks with multispecies coalescent methods and morphology.

While methods for genetic species delimitation have noticeably improved in the last decade, this remains a work in progress. Ideally, model based approaches should be applied and considered jointly with other lines of evidence, primarily morphology and geography, in an integrative taxonomy framework. Deep phylogeographic divergences have been reported for several species of skinks, but only for some eastern taxa have species boundaries been formally tested.

StarBEAST2 Brings Faster Species Tree Inference and Accurate Estimates of Substitution Rates.

Fully Bayesian multispecies coalescent (MSC) methods like *BEAST estimate species trees from multiple sequence alignments. Today thousands of genes can be sequenced for a given study, but using that many genes with *BEAST is intractably slow. An alternative is to use heuristic methods which compromise accuracy or completeness in return for speed.

Fungal phytopathogens encode functional homologues of plant rapid alkalinization factor (RALF) peptides.

In this article, we describe the presence of genes encoding close homologues of an endogenous plant peptide, rapid alkalinization factor (RALF), within the genomes of 26 species of phytopathogenic fungi. Members of the RALF family are key growth factors in plants, and the sequence of the RALF active region is well conserved between plant and fungal proteins. RALF1-like sequences were observed in most cases; however, RALF27-like sequences were present in the Sphaerulina musiva and Septoria populicola genomes.

Computational Performance and Statistical Accuracy of *BEAST and Comparisons with Other Methods.

Under the multispecies coalescent model of molecular evolution, gene trees have independent evolutionary histories within a shared species tree. In comparison, supermatrix concatenation methods assume that gene trees share a single common genealogical history, thereby equating gene coalescence with species divergence. The multispecies coalescent is supported by previous studies which found that its predicted distributions fit empirical data, and that concatenation is not a consistent estimator of the species tree.

Diversification of the C-TERMINALLY ENCODED PEPTIDE (CEP) gene family in angiosperms, and evolution of plant-family specific CEP genes.

Background: Small, secreted signaling peptides work in parallel with phytohormones to control important aspects of plant growth and development. Genes from the C-TERMINALLY ENCODED PEPTIDE (CEP) family produce such peptides which negatively regulate plant growth, especially under stress, and affect other important developmental processes. To illuminate how the CEP gene family has evolved within the plant kingdom, including its emergence, diversification and variation between lineages, a comprehensive survey was undertaken to identify and characterize CEP genes in 106 plant genomes.

The peptide-encoding CEP1 gene modulates lateral root and nodule numbers in Medicago truncatula.

The role of MtCEP1, a member of the CEP (C-terminally encoded peptide) signaling peptide family, was examined in Medicago truncatula root development. MtCEP1 was expressed in root tips, vascular tissue, and young lateral organs, and was up-regulated by low nitrogen levels and, independently, by elevated CO2. Overexpressing MtCEP1 or applying MtCEP1 peptide to roots elicited developmental phenotypes: inhibition of lateral root formation, enhancement of nodulation, and the induction of periodic circumferential root swellings, which arose from cortical, epidermal, and pericycle cell divisions and featured an additional cortical cell layer.