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Genomic resources for amphibians are still hugely under-represented in vertebrate genomic research, despite being a group of major interest for ecology, evolution and conservation. Amphibians constitute a highly threatened group of vertebrates, present a vast diversity in reproductive modes, are extremely diverse in morphology, occupy most ecoregions of the world, and present the widest range in genome sizes of any major group of vertebrates. We combined Illumina, Nanopore and Hi-C sequencing technologies to assemble a chromosome-level genome sequence for an anuran with a moderate genome size (assembly span 3.09 Gb); Pelobates cultripes, the western spadefoot toad. The genome has an N50 length of 330 Mb with 98.6% of the total sequence length assembled into 14 super scaffolds, and 87.7% complete BUSCO genes. We use published transcriptomic data to provide annotations, identifying 32,684 protein-coding genes. We also reconstruct the P. cultripes phylome and identify 2,527 gene expansions. We contribute the first draft of the genome of the western spadefoot toad, P. cultripes. This species represents a relatively basal lineage in the anuran tree with an interesting ecology and a high degree of developmental plasticity, and thus is an important resource for amphibian genomic research. This research was funded by Plan Nacional I + D grant #CGL2017-83407-P awarded to I.G.-M. and a Ministerio de Ciencia e Innovación fellowship #IJC2018-035780-I awarded to H.C.L. TG’s group acknowledges support from the Spanish Ministry of Science and Innovation for grant PGC2018-099921-B-I00, cofounded by European Regional Development Fund (ERDF); and from the European Union’s Horizon 2020 research and innovation programme (ERC-2016-724173).

Candida parapsilosis species complex comprises three important pathogenic species: Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis. The majority of C. orthopsilosis and all C. metapsilosis isolates sequenced thus far are hybrids, and most of the parental lineages remain unidentified. This led to the hypothesis that hybrids with pathogenic potential were formed by the hybridization of non-pathogenic lineages that thrive in the environment. In a search for the missing hybrid parentals, and aiming to get a better understanding of the evolution of the species complex, we sequenced, assembled and analysed the genome of five close relatives isolated from the environment: Candida jiufengensis, Candida pseudojiufengensis, Candida oxycetoniae, Candida margitis and Candida theae. We found that the linear conformation of mitochondrial genomes in Candida species emerged multiple times independently. Furthermore, our analyses discarded the possible involvement of these species in the mentioned hybridizations, but identified C. theae as an additional hybrid in the species complex. Importantly, C. theae was recently associated with a case of infection, and we also uncovered the hybrid nature of this clinical isolate. Altogether, our results reinforce the hypothesis that hybridization is widespread among Candida species, and potentially contributes to the emergence of lineages with opportunistic pathogenic behaviour. This work received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie Grant Agreement No. H2020-MSCA-ITN-2014-642095. T.G. group also acknowledges support from the Spanish Ministry of Science and Innovation for grant PGC2018-099921-B-I00, cofounded by European Regional Development Fund (ERDF); from the Catalan Research Agency (AGAUR) SGR423; from the European Union’s Horizon 2020 research and innovation programme (ERC-2016-724173); from the Gordon and Betty Moore Foundation (Grant GBMF9742) and from the Instituto de Salud Carlos III (INB Grant PT17/0009/0023—ISCIII-SGEFI/ERDF). J.N. group was supported by the Slovak Research and Development Agency (APVV-18-0239, APVV-20-0166) and the Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic (VEGA 1/0027/19).

Background: Recent technological developments have made genome sequencing and assembly highly accessible and widely used. However, the presence in sequenced organisms of certain genomic features such as high heterozygosity, polyploidy, aneuploidy, heterokaryosis, or extreme compositional biases can challenge current standard assembly procedures and result in highly fragmented assemblies. Hence, we hypothesized that genome databases must contain a nonnegligible fraction of low-quality assemblies that result from such type of intrinsic genomic factors. Findings: Here we present Karyon, a Python-based toolkit that uses raw sequencing data and de novo genome assembly to assess several parameters and generate informative plots to assist in the identification of nonchanonical genomic traits. Karyon includes automated de novo genome assembly and variant calling pipelines. We tested Karyon by diagnosing 35 highly fragmented publicly available assemblies from 19 different Mucorales (Fungi) species. Conclusions: Our results show that 10 (28.57%) of the assemblies presented signs of unusual genomic configurations, suggesting that these are common, at least for some lineages within the Fungi. Supported by the Spanish Ministry of Science and Innovation (grant PGC2018-099921-B-I00), cofounded by the European Regional Development Fund (ERDF); the Catalan Research Agency (AGAUR), SGR423; the European Union's Horizon 2020 research and innovation program (ERC-2016–724173); the Gordon and Betty Moore Foundation (grant GBMF9742); and the Instituto de Salud Carlos III (IMPACT grant IMP/00019 and CIBERINFEC CB21/13/00061-ISCIII-SGEFI/ERDF).

SUMMARY: An increasing number of phased (i.e. with resolved haplotypes) reference genomes are available. However, the most genetic variant calling tools do not explicitly account for haplotype structure. Here, we present HaploTypo, a pipeline tailored to resolve haplotypes in genetic variation analyses. HaploTypo infers the haplotype correspondence for each heterozygous variant called on a phased reference genome. AVAILABILITY AND IMPLEMENTATION: HaploTypo is implemented in Python 2.7 and Python 3.5, and is freely available at https://github.com/gabaldonlab/haplotypo, and as a Docker image. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. This work was supported by the European Union’s Horizon 2020 research and innovation programme under the grant agreement ERC-2016-724173 and Marie Sklodowska-Curie grant agreements N° 642095, and 747607; the Spanish Ministry of Economy, Industry, and Competitiveness (MEIC) for the EMBL partnership, and grants ‘Centro de Excelencia Severo Ochoa’ SEV-2012-0208, and BFU2015-67107 co-founded by European Regional Development Fund (ERDF); the CERCA Programme/Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR857; and INB Grant (PT17/0009/0023—ISCIII-SGEFI/ERDF).

Aphids (Aphidoidea) are a diverse group of hemipteran insects that feed on plant phloem sap. A common finding in studies of aphid genomes is the presence of a large number of duplicated genes. However, when these duplications occurred remains unclear, partly due to the high relatedness of sequenced species. To better understand the origin of aphid duplications we sequenced and assembled the genome of Cinara cedri, an early branching lineage (Lachninae) of the Aphididae family. We performed a phylogenomic comparison of this genome with 20 other sequenced genomes, including the available genomes of five other aphids, along with the transcriptomes of two species belonging to Adelgidae (a closely related clade to the aphids) and Coccoidea. We found that gene duplication has been pervasive throughout the evolution of aphids, including many parallel waves of recent, species-specific duplications. Most notably, we identified a consistent set of very ancestral duplications, originating from a large-scale gene duplication predating the diversification of Aphidomorpha (comprising aphids, phylloxerids, and adelgids). Genes duplicated in this ancestral wave are enriched in functions related to traits shared by Aphidomorpha, such as association with endosymbionts, and adaptation to plant defenses and phloem-sap-based diet. The ancestral nature of this duplication wave (106–227 Ma) and the lack of sufficiently conserved synteny make it difficult to conclude whether it originated from a whole-genome duplication event or, alternatively, from a burst of large-scale segmental duplications. Genome sequencing of other aphid species belonging to different Aphidomorpha and related lineages may clarify these findings., This research was funded by European Regional Development Fund (ERDF) and Ministerio de Economía y Competitividad (Spain) (Grant Nos. PGC2018-099344-B-100 and BFU2015-67107). T.G. group also acknowledges support from the Catalan Research Agency (AGAUR) SGR857, and grants from the European Union’s Horizon 2020 research and innovation program under the grant agreements ERC-2016-724173 and MSC-747607. T.G. also receives support from an INB (Grant No. PT17/0009/0023—ISCIII-SGEFI/ERDF).

Candida subhashii belongs to the CUG-Ser clade, a group of phylogenetically closely related yeast species that includes some human opportunistic pathogens, such as Candida albicans. Despite being present in the environment, C. subhashii was initially described as the causative agent of a case of peritonitis. Considering the relevance of whole-genome sequencing and analysis for our understanding of genome evolution and pathogenicity, we sequenced, assembled and annotated the genome of C. subhashii type strain. Our results show that C. subhashii presents a highly heterozygous genome and other signatures that point to a hybrid ancestry. The presence of functional pathways for assimilation of hydroxyaromatic compounds goes in line with the affiliation of this yeast with soil microbial communities involved in lignin decomposition. Furthermore, we observed that different clones of this strain may present circular or linear mitochondrial DNA. Re-sequencing and comparison of strains with differential mitochondrial genome topology revealed five candidate genes potentially associated with this conformational change: MSK1, SSZ1, ALG5, MRPL9 and OYE32. This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement No. H2020-MSCA-ITN-2014-642095. T.G. group also acknowledges support from the Spanish Ministry of Economy, Industry, and Competitiveness (MEIC) for the EMBL partnership, and grants ‘Centro de Excelencia Severo Ochoa 2013-2017’ SEV-2012-0208 and BFU2015-67107 co-founded by European Regional Development Fund (ERDF); from the CERCA Programme/Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR857, and grants from the European Union’s Horizon 2020 Research and Innovation Programme under the grant agreement ERC-2016-724173. T.G. also receives support from an INB Grant (PT17/0009/0023 - ISCIII-SGEFI/ERDF). J.N. group was supported by the Slovak Research and Development Agency (APVV-18-0239) and the Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic (VEGA 1/0027/19).

The modification of adenosine to inosine at the wobble position (I34) of tRNA anticodons is an abundant and essential feature of eukaryotic tRNAs. The expansion of inosine-containing tRNAs in eukaryotes followed the transformation of the homodimeric bacterial enzyme TadA, which generates I34 in tRNAArg and tRNALeu, into the heterodimeric eukaryotic enzyme ADAT, which modifies up to eight different tRNAs. The emergence of ADAT and its larger set of substrates, strongly influenced the tRNA composition and codon usage of eukaryotic genomes. However, the selective advantages that drove the expansion of I34-tRNAs remain unknown. Here we investigate the functional relevance of I34-tRNAs in human cells and show that a full complement of these tRNAs is necessary for the translation of low-complexity protein domains enriched in amino acids cognate for I34-tRNAs. The coding sequences for these domains require codons translated by I34-tRNAs, in detriment of synonymous codons that use other tRNAs. I34-tRNA-dependent low-complexity proteins are enriched in functional categories related to cell adhesion, and depletion in I34-tRNAs leads to cellular phenotypes consistent with these roles. We show that the distribution of these low-complexity proteins mirrors the distribution of I34-tRNAs in the phylogenetic tree. Spanish Ministry of Economy and Competitiveness [PID2019-108037RB-100 to L.R.d.P., PGC2018-099921 to T.G., PGC2018-098152-A-100 to E.M.N]; Australian Research Council [DP180103571 to E.M.N]; European Union's Horizon 2020 research and innovation programme [ERC-2016–724173 to T.G.]. Funding for open access charge: Spanish Ministry of Economy and Competitiveness. Peer Reviewed "Article signat per 14 autors/es: Adrian Gabriel Torres, Marta Rodríguez-Escribà, Marina Marcet-Houben, Helaine Graziele Santos Vieira, Noelia Camacho, Helena Catena, Marina Murillo Recio, Àlbert Rafels-Ybern, Oscar Reina, Francisco Miguel Torres, Ana Pardo-Saganta, Toni Gabaldón, Eva Maria Novoa, Lluís Ribas de Pouplana"

PhylomeDB is a unique knowledge base providing public access to minable and browsable catalogues of pre-computed genome-wide collections of annotated sequences, alignments and phylogenies (i.e. phylomes) of homologous genes, as well as to their corresponding phylogeny-based orthology and paralogy relationships. In addition, PhylomeDB trees and alignments can be downloaded for further processing to detect and date gene duplication events, infer past events of inter-species hybridization and horizontal gene transfer, as well as to uncover footprints of selection, introgression, gene conversion, or other relevant evolutionary processes in the genes and organisms of interest. Here, we describe the latest evolution of PhylomeDB (version 5). This new version includes a newly implemented web interface and several new functionalities such as optimized searching procedures, the possibility to create user-defined phylome collections, and a fully redesigned data structure. This release also represents a significant core data expansion, with the database providing access to 534 phylomes, comprising over 8 million trees, and homology relationships for genes in over 6000 species. This makes PhylomeDB the largest and most comprehensive public repository of gene phylogenies. PhylomeDB is available at http://www.phylomedb.org. Spanish Ministry of Science and Innovation (MICINN) [PGC2018-099921-B-I00], cofounded by European Regional Development Fund (ERDF); Catalan Research Agency (AGAUR) [SGR423]; European Union's Horizon 2020 research and innovation programme [ERC-2016–724173]; Gordon and Betty Moore Foundation [GBMF9742]; Instituto de Salud Carlos III [INB Grant PT17/0009/0023 – ISCIII-SGEFI/ERDF]; U.C. was funded in part through H2020 Marie Skłodowska-Curie Actions [H2020-MSCA-IF-2017-793699]; MICINN [IJC2019- 039402-I]. Funding for open access charge: ERC.

[Motivation]: Sequence analyses oriented to investigate specific features, patterns and functions of protein and DNA/RNA sequences usually require tools based on graphic interfaces whose main characteristic is their intuitiveness and interactivity with the user’s expertise, especially when curation or primer design tasks are required. However, interface-based tools usually pose certain computational limitations when managing large sequences or complex datasets, such as genome and transcriptome assemblies. Having these requirments in mind we have developed SeqEditor an interactive software tool for nucleotide and protein sequences’ analysis., [Result]: SeqEditor is a cross-platform desktop application for the analysis of nucleotide and protein sequences. It is managed through a Graphical User Interface and can work either as a graphical sequence browser or as a fasta task manager for multi-fasta files. SeqEditor has been optimized for the management of large sequences, such as contigs, scaffolds or even chromosomes, and includes a GTF/GFF viewer to visualize and manage annotation files. In turn, this allows for content mining from reference genomes and transcriptomes with similar efficiency to that of command line tools. SeqEditor also incorporates a set of tools for singleplex and multiplex PCR primer design and pooling that uses a newly optimized and validated search strategy for target and species-specific primers. All these features make SeqEditor a flexible application that can be used to analyses complex sequences, design primers in PCR assays oriented for diagnosis, and/or manage, edit and personalize reference sequence datasets., This work was supported by the European Union’s Horizon 2020 Research and Innovation programme under the Marie Sklodowska-Curie grant agreement [642095] of the OPATHY consortium; by the pre-doctoral research fellowship from Industrial Doctorates of MINECO [DI-17-09134]; and by the State Plan for Scientific and Technical Research and Innovation 2017-2020 of the Secretary of State for Digital Advancement of Ministry of Economic Affairs and Digital Transformation, Spain [TSI-100903-2019-11].

Ecology of insects is as wide as their diversity, which reflects their high capacity of adaptation in most of the environments of our planet. Aphids, with over 4,000 species, have developed a series of adaptations including a high phenotypic plasticity and the ability to feed on the phloem sap of plants, which is enriched in sugars derived from photosynthesis. Recent analyses of aphid genomes have indicated a high level of shared ancestral gene duplications that might represent a basis for genetic innovation and broad adaptations. In addition, there are a large number of recent, species-specific gene duplications whose role in adaptation remains poorly understood. Here, we tested whether duplicates specific to the pea aphid Acyrthosiphon pisum are related to genomic innovation by combining comparative genomics, transcriptomics, and chromatin accessibility analyses. Consistent with large levels of neofunctionalization, we found that most of the recent pairs of gene duplicates evolved asymmetrically, showing divergent patterns of positive selection and gene expression. Genes under selection involved a plethora of biological functions, suggesting that neofunctionalization and tissue specificity, among other evolutionary mechanisms, have orchestrated the evolution of recent paralogs in the pea aphid and may have facilitated host-symbiont cooperation. Our comprehensive phylogenomics analysis allowed us to tackle the history of duplicated genes to pave the road toward understanding the role of gene duplication in ecological adaptation., R.F. was funded by a Juan de la Cierva-Incorporacion Fellowship (Government of Spain, IJCI-2015-26627) and a Marie Skłodowska-Curie Fellowship (747607). T.G. acknowledges support from the Spanish Ministry of Economy, Industry, and Competitiveness (MEIC) for the EMBL partnership, and grants “Centro de Excelencia Severo Ochoa 2013– 2017” SEV-2012-0208, and BFU2015-67107 cofunded by European Regional Development Fund (ERDF); from the CERCA Programme/Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR857, and grant from the European Union’s Horizon 2020 research and innovation program under the grant agreement ERC-2016-724173 and the Marie Sklodowska-Curie (Grant Agreement No. H2020-MSCA-ITN-2014-642095). D.T. was funded by “Severo Ochoa visiting scientific program” for a 6 months stay at the Center for Genomic Regulation—Barcelona—to start the project, supported as well by INRA SPE. Dr Roderic Guigo (CRG, Barcelona) is warmly acknowledged for his welcome in his lab. Dr Akiko Sugio, Dr Julie Jaquiery, Dr Ga€el Le Trionnaire, and Dr Jean-Christophe Simon (INRAE, UMR 1349 Igepp, Rennes, France) are acknowledged for access to unpublished data of RNA-Seq. Daktulosphaira vitifoliae data were provided by the Phylloxera Genome Project (https://bipaa. genouest.org/is/aphidbase/): funding for D. vitifoliae clone Pcf genomic sequencing was provided by INRA (AIP Bioresources) and BGI Biotech in the frame of i5k initiative. Parts of the transcriptomic resources were obtained within the 1KITE projects (Bernhard Misof, Bonn, Germany). The Acyrthosiphon pisum phylome can be accessed at PhylomeDB 4.0 under phylome number 441. RNA-Seq data are accessible at NCBI, see supplementary table S2, Supplementary Material online.

Motivation Numerous sequencing studies, including transcriptomics of host-pathogen systems, sequencing of hybrid genomes, xenografts, mixed species systems, metagenomics and meta-transcriptomics, involve samples containing genetic material from divergent organisms. A crucial step in these studies is identifying from which organism each sequencing read originated, and the experimental design should be directed to minimize biases caused by cross-mapping of reads to incorrect source genomes. Additionally, pooling of sufficiently different genetic material into a single sequencing library could significantly reduce experimental costs but requires careful planning and assessment of the impact of cross-mapping. Having these applications in mind we designed Crossmapper, the first to our knowledge tool able to assess cross-mapping prior to sequencing, therefore allowing optimization of experimental design. Results Using any combination of reference genomes, Crossmapper performs read simulation and back-mapping of those reads to the pool of references, quantifies and reports the cross-mapping rates for each organism. Crossmapper performs these analyses with numerous user-specified parameters, including, among others, read length, read layout, coverage, mapping parameters, genomic or transcriptomic data. Additionally, it outputs the results in highly interactive and publication-ready reports. This allows the user to perform multiple comparisons at once and choose the experimental setup minimizing cross-mapping rates. Moreover, Crossmapper can be used for resource optimization in sequencing facilities by pooling different samples into one sequencing library. Availability and implementation Crossmapper is a command line tool implemented in Python 3.6 and available as a conda package, allowing effortless installation. The source code, detailed information and a step-by-step tutorial is available at our GitHub page https://github.com/Gabaldonlab/crossmapper. Supplementary information Supplementary data are available at Bioinformatics online. This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) for the EMBL partnership and the grant ‘Centro de Excelencia Severo Ochoa’ SEV-2012-0208 cofounded by European Regional Development Fund (ERDF); from the CERCA Programme/Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR857 and grants from the European Union’s Horizon 2020 research and innovation programme under the grant agreement ERC-2016-724173 and the Marie Sklodowska-Curie grant agreement No H2020-MSCA-ITN-2014-642095. The group also receives support from a INB Grant (PT17/0009/0023–ISCIII-SGEFI/ERDF).

Aging is a complex process affecting different species and individuals in different ways. Comparing genetic variation across species with their aging phenotypes will help understanding the molecular basis of aging and longevity. Although most studies on aging have so far focused on short-lived model organisms, recent comparisons of genomic, transcriptomic, and metabolomic data across lineages with different lifespans are unveiling molecular signatures associated with longevity. Here, we examine the relationship between genomic variation and maximum lifespan across primate species. We used two different approaches. First, we searched for parallel amino-acid mutations that co-occur with increases in longevity across the primate linage. Twenty-five such amino-acid variants were identified, several of which have been previously reported by studies with different experimental setups and in different model organisms. The genes harboring these mutations are mainly enriched in functional categories such as wound healing, blood coagulation, and cardiovascular disorders. We demonstrate that these pathways are highly enriched for pleiotropic effects, as predicted by the antagonistic pleiotropy theory of aging. A second approach was focused on changes in rates of protein evolution across the primate phylogeny. Using the phylogenetic generalized least squares, we show that some genes exhibit strong correlations between their evolutionary rates and longevity-associated traits. These include genes in the Sphingosine 1-phosphate pathway, PI3K signaling, and the Thrombin/protease-activated receptor pathway, among other cardiovascular processes. Together, these results shed light into human senescence patterns and underscore the power of comparative genomics to identify pathways related to aging and longevity. This work was supported by Ministerio de Ciencia e Innovación, Spain (BFU2012-38236 and BFU2015-68649-P (MINECO/FEDER, UE) to AN), by Direcció General de Recerca, Generalitat de Catalunya (2014SGR1311 and 2014SGR866 to A.N., and 2014BP-B00157 to G.M.), by the Spanish National Institute of Bioinfomatics of the Instituto de Salud Carlos III (PT13/0001/0026), by “Unidad de Excelencia María de Maeztu”, funded by the MINECO (ref: MDM-2014-0370), and by FEDER (Fondo Europeo de Desarrollo Regional)/FSE (Fondo Social Europeo)

Phylogenetic trees representing the evolutionary relationships of homologous genes are the entry point for many evolutionary analyses. For instance, the use of a phylogenetic tree can aid in the inference of orthology and paralogy relationships, and in the detection of relevant evolutionary events such as gene family expansions and contractions, horizontal gene transfer, recombination or incomplete lineage sorting. Similarly, given the plurality of evolutionary histories among genes encoded in a given genome, there is a need for the combined analysis of genome-wide collections of phylogenetic trees (phylomes). Here, we introduce a new release of PhylomeDB (http://phylomedb.org), a public repository of phylomes. Currently, PhylomeDB hosts 120 public phylomes, comprising >1.5 million maximum likelihood trees and multiple sequence alignments. In the current release, phylogenetic trees are annotated with taxonomic, protein-domain arrangement, functional and evolutionary information. PhylomeDB is also a major source for phylogeny-based predictions of orthology and paralogy, covering >10 million proteins across 1059 sequenced species. Here we describe newly implemented PhylomeDB features, and discuss a benchmark of the orthology predictions provided by the database, the impact of proteome updates and the use of the phylome approach in the analysis of newly sequenced genomes and transcriptomes. Spanish ministry of Economy and Competitiveness [BIO2012-37161]; a Grant from the Qatar National/nResearch Fund [NPRP 5-298-3-086]; a the European Research Council under the European Union’s Seventh/nFramework Programme [FP/2007-2013/ERC and ERC-/n2012-StG-310325]; Juan de La Cierva postdoctoral program (to J.H.C.) and La Caixa-CRG International Fellowship Program (to L.P.P.). Funding for open access charge: Internal budget from the CRG

Saccharomycotina comprises a diverse group of yeasts that includes numerous species of industrial or clinical relevance. Opportunistic pathogens within this clade are often assigned to the genus Candida but belong to phylogenetically distant lineages that also comprise non-pathogenic species. This indicates that the ability to infect humans has evolved independently several times among Saccharomycotina. Although the mechanisms of infection of the main groups of Candida pathogens are starting to be unveiled, we still lack sufficient understanding of the evolutionary paths that led to a virulent phenotype in each of the pathogenic lineages. Deciphering what genomic changes underlie the evolutionary emergence of a virulence trait will not only aid the discovery of novel virulence mechanisms but it will also provide valuable information to understand how new pathogens emerge, and what clades may pose a future danger. Here we review recent comparative genomics efforts that have revealed possible evolutionary paths to pathogenesis in different lineages, focusing on the main three agents of candidiasis worldwide: Candida albicans, C. parapsilosis and C. glabrata. We will discuss what genomic traits may facilitate the emergence of virulence, and focus on two different genome evolution mechanisms able to generate drastic phenotypic changes and which have been associated to the emergence of virulence: gene family expansion and interspecies hybridization., The growing availability of genomic information from the increasingly relevant Candida pathogens is helping us to unravel their recent evolution.

The growing availability of complete genomic sequences from diverse species has brought about the need to scale up phylogenomic analyses, including the reconstruction of large collections of phylogenetic trees. Here, we present the third version of PhylomeDB (http://phylomeDB.org), a public database for genome-wide collections of gene phylogenies (phylomes). Currently, PhylomeDB is the largest phylogenetic repository and hosts 17 phylomes, comprising 416 093 trees and 165 840 alignments. It is also a major source for phylogeny-based orthology and paralogy predictions, covering about 5 million proteins in 717 fully-sequenced genomes. For each protein-coding gene in a seed genome, the database provides original and processed alignments, phylogenetic trees derived from various methods and phylogeny-based predictions of orthology and paralogy relationships. The new version of phylomeDB has been extended with novel data access and visualization features, including the possibility of programmatic access. Available seed species include model organisms such as human, yeast, Escherichia coli or Arabidopsis thaliana, but also alternative model species such as the human pathogen Candida albicans, or the pea aphid Acyrtosiphon pisum. Finally, PhylomeDB is currently being used by several genome sequencing projects that couple the genome annotation process with the reconstruction of the corresponding phylome, a strategy that provides relevant evolutionary insights.

Peroxisomes are essential organelles that play a key role in redox signalling and lipid homeostasis. They contain a highly diverse enzymatic network among different species, mirroring the varied metabolic needs of the organisms. The previous PeroxisomeDB version organized the peroxisomal proteome of humans and Saccharomyces cerevisiae based on genetic and functional information into metabolic categories with a special focus on peroxisomal disease. The new release (http://www.peroxisomeDB.org) adds peroxisomal proteins from 35 newly sequenced eukaryotic genomes including fungi, yeasts, plants and lower eukaryotes. We searched these genomes for a core ensemble of 139 peroxisomal protein families and identified 2706 putative peroxisomal protein homologs. Approximately 37% of the identified homologs contained putative peroxisome targeting signals (PTS). To help develop understanding of the evolutionary relationships among peroxisomal proteins, the new database includes phylogenetic trees for 2386 of the peroxisomal proteins. Additional new features are provided, such as a tool to capture kinetic information from Brenda, CheBI and Sabio-RK databases and more than 1400 selected bibliographic references. PeroxisomeDB 2.0 is a freely available, highly interactive functional genomics platform that offers an extensive view on the peroxisomal metabolome across lineages, thus facilitating comparative genomics and systems analysis of the organelle.

Reconstructing the evolutionary relationships of species is a major goal in biology. Despite the increasing number of completely sequenced genomes, a large number of phylogenetic projects rely on targeted sequencing and analysis of a relatively small sample of marker genes. The selection of these phylogenetic markers should ideally be based on accurate predictions of their combined, rather than individual, potential to accurately resolve the phylogeny of interest. Here we present and validate a new phylogenomics strategy to efficiently select a minimal set of stable markers able to reconstruct the underlying species phylogeny. In contrast to previous approaches, our methodology does not only rely on the ability of individual genes to reconstruct a known phylogeny, but it also explores the combined power of sets of concatenated genes to accurately infer phylogenetic relationships of species not previously analyzed. We applied our approach to two broad sets of cyanobacterial and ascomycetous fungal species, and provide two minimal sets of six and four genes, respectively, necessary to fully resolve the target phylogenies. This approach paves the way for the informed selection of phylogenetic markers in the effort of reconstructing the tree of life.

Invasive candidiasis is the most commonly reported invasive fungal infection worldwide. Although Candida albicans remains the main cause, the incidence of emerging Candida species, such as C. parapsilosis is increasing. It has been postulated that C. parapsilosis clinical isolates result from a recent global expansion of a virulent clone. However, the availability of a single genome for this species has so far prevented testing this hypothesis at genomic scales. We present here the sequence of three additional strains from clinical and environmental samples. Our analyses reveal unexpected patterns of genomic variation, shared among distant strains, that argue against the clonal expansion hypothesis. All strains carry independent expansions involving an arsenite transporter homolog, pointing to the existence of directional selection in the environment, and independent origins of the two clinical isolates. Furthermore, we report the first evidence for the existence of recombination in this species. Altogether, our results shed new light onto the dynamics of genome evolution in C. parapsilosis. This work was supported by the La Caixa-CRG International Fellowship Program to L.P., the TAMOP 4.2.4. A/2-11-1-2012-001 “National Excellence Program” to T.N., and was supported in part by OTKA NF 84006, NN00374 (ERA-Net/nPathoGenomics Program), EMBO Installation Grant and by the Janos Bolyai Fellowship of the Hungarian Academy of Sciences to A.G. T.G. group research is funded in part by a grant from the Spanish Ministry of Economy and Competitiveness (BIO2012-37161), a grant from the Qatar National Research Fund grant (NPRP 5-298-3-086), and a grant from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC (grant agreement no. ERC-/n2012-StG-310325)

Transferrin is a protein super-family involved in iron transport, a central process in cellular homeostasis. Throughout the evolution of vertebrates, transferrin members have diversified into distinct subfamilies including serotransferrin, ovotransferrin, lactoferrin, melanotransferrin, the inhibitor of carbonic anhydrase, pacifastin, and the major yolk protein in sea urchin. Previous phylogenetic analyses have established the branching order of the diverse transferrin subfamilies but were mostly focused on the transferrin repertoire present in mammals. Here, we conduct a comprehensive phylogenetic analysis of transferrin protein sequences in sequenced vertebrates, placing a special focus on the less-studied nonmammalian vertebrates. Our analyses uncover a novel transferrin clade present across fish, sauropsid, and amphibian genomes but strikingly absent from mammals. Our reconstructed scenario implies that this novel class emerged through a duplication event at the vertebrate ancestor, and that it was subsequently lost in the lineage leading to mammals. We detect footprints of accelerated evolution following the duplication event, which suggest positive selection and early functional divergence of this novel clade. Interestingly, the loss of this novel class of transferrin in mammals coincided with the divergence by duplication of lactoferrin and serotransferrin in this lineage. Altogether, our results provide novel insights on the evolution of iron-binding proteins in the various vertebrate groups. This work was supported by grants from the Malaysian Ministry of Science, Technology and Innovation (07-05-MGI-GMB009), the Spanish Ministry of Science and Innovation (BFU2009-09168), and Universiti Kebangsaan Malaysia (UKM-DLP-2011-027)

The yeast Candida glabrata is an opportunistic human fungal pathogen whose incidence has increased in the last two decades. Despite its name, this yeast is only distantly related to the model fungal pathogen C. albicans, and more closely related to Saccharomyces cerevisiae and other yeasts that underwent an ancient whole-genome duplication. Understanding what specific traits make C. glabrata a successful opportunistic pathogen within a clade of mostly innocuous yeasts, and how these compare to virulence traits in distant pathogens such as C. albicans is a focus of intense research. From an evolutionary perspective, uncovering how the ability to infect humans has emerged multiple, independent times in different lineages may reveal new disease mechanisms and provide us with the capacity to predict which genomic features in a clade may confer a higher potential to develop virulence against humans., Candida glabrata is an opportunistic human pathogen; genomics analyses have revealed its evolutionary path to virulence.

Peroxisomes are essential organelles of eukaryotic origin, ubiquitously distributed in cells and organisms, playing key roles in lipid and antioxidant metabolism. Loss or malfunction of peroxisomes causes more than 20 fatal inherited conditions. We have created a peroxisomal database (http://www.peroxisomeDB.org) that includes the complete peroxisomal proteome of Homo sapiens and Saccharomyces cerevisiae, by gathering, updating and integrating the available genetic and functional information on peroxisomal genes. PeroxisomeDB is structured in interrelated sections 'Genes', 'Functions', 'Metabolic pathways' and 'Diseases', that include hyperlinks to selected features of NCBI, ENSEMBL and UCSC databases. We have designed graphical depictions of the main peroxisomal metabolic routes and have included updated flow charts for diagnosis. Precomputed BLAST, PSI-BLAST, multiple sequence alignment (MUSCLE) and phylogenetic trees are provided to assist in direct multispecies comparison to study evolutionary conserved functions and pathways. Highlights of the PeroxisomeDB include new tools developed for facilitating (i) identification of novel peroxisomal proteins, by means of identifying proteins carrying peroxisome targeting signal (PTS) motifs, (ii) detection of peroxisomes in silico, particularly useful for screening the deluge of newly sequenced genomes. PeroxisomeDB should contribute to the systematic characterization of the peroxisomal proteome and facilitate system biology approaches on the organelle.