Age-dependent changes in the specificity of tRNA methyltransferases in the cerebellum of the icteric and nonicteric Gunn rat

The activity of tRNA methyltransferases present in the cerebellum of 6- and 21-day-old nonicteric and icteric Gunn rats was compared using purified E. coli tRNAs as substrates. At 6 days the tRNA methyltransferases of the icteric animals were significantly more effective in methylating tRNA Glu 2 and tRNA Phe than were those of their nonicteric counterparts. This relationship reversed itself at 21 days. The action of the tRNA methyltransferases from the 6-day-old icteric animals led to higher proportions of 1-methyladenine in tRNA Glu 2 and tRNA Phe than were obtained using the corresponding enzymes of the nonicteric animals. The proportion of N 2 -methylguanine was also higher, yet only in tRNA fMet and not in tRNA Phe . The study reveals much more extensive fluctuations in the activity and in the substrate recognition specificity among the cerebellar tRNA methyltransferases of the icteric than among those of the nonicteric controls during the crucial 6–21 day period of cerebellar development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45425/1/11064_2004_Article_BF00964433.pd

Assembly and analysis of the genome sequence of the yeast Brettanomyces naardenensis CBS 7540

Brettanomyces naardenensis is a spoilage yeast with potential for biotechnological applications for production of innovative beverages with low alcohol content and high attenuation degree. Here, we present the first annotated genome of B. naardenensis CBS 7540. The genome of B. naardenensis CBS 7540 was assembled into 76 contigs, totaling 11,283,072 nucleotides. In total, 5168 protein-coding sequences were annotated. The study provides functional genome annotation, phylogenetic analysis, and discusses genetic determinants behind notable stress tolerance and biotechnological potential of B. naardenensis

Genomic analyses of the Linum distyly supergene reveal convergent evolution at the molecular level

Supergenes govern multi-trait-balanced polymorphisms in a wide range of systems; however, our understanding of their origins and evolution remains incomplete. The reciprocal placement of stigmas and anthers in pin and thrum floral morphs of distylous species constitutes an iconic example of a balanced polymorphism governed by a supergene, the distyly S-locus. Recent studies have shown that the Primula and Turnera distyly supergenes are both hemizygous in thrums, but it remains unknown whether hemizygosity is pervasive among distyly S-loci. As hemizygosity has major consequences for supergene evolution and loss, clarifying whether this genetic architecture is shared among distylous species is critical. Here, we have characterized the genetic architecture and evolution of the distyly supergene in Linum by generating a chromosome-level genome assembly of Linum tenue, followed by the identification of the S-locus using population genomic data. We show that hemizygosity and thrum-specific expression of S-linked genes, including a pistil-expressed candidate gene for style length, are major features of the Linum S-locus. Structural variation is likely instrumental for recombination suppression, and although the non-recombining dominant haplotype has accumulated transposable elements, S-linked genes are not under relaxed purifying selection. Our findings reveal remarkable convergence in the genetic architecture and evolution of independently derived distyly supergenes, provide a counterexample to classic inversion-based supergenes, and shed new light on the origin and maintenance of an iconic floral polymorphism.European Research Council (ERC) 757451Swedish Research Council 2019-04452, 2018-0597

Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates

SLC22A10 is classified as an orphan transporter with unknown substrates and function. Here we describe the discovery of the substrate specificity and functional characteristics of SLC22A10. The human SLC22A10 tagged with green fluorescent protein was found to be absent from the plasma membrane, in contrast to the SLC22A10 orthologs found in great apes. Estradiol-17β-glucuronide accumulated in cells expressing great ape SLC22A10 orthologs (over 4-fold, p<0.001). In contrast, human SLC22A10 displayed no uptake function. Sequence alignments revealed two amino acid differences including a proline at position 220 of the human SLC22A10 and a leucine at the same position of great ape orthologs. Site-directed mutagenesis yielding the human SLC22A10-P220L produced a protein with excellent plasma membrane localization and associated uptake function. Neanderthal and Denisovan genomes show human-like sequences at proline 220 position, corroborating that SLC22A10 were rendered nonfunctional during hominin evolution after the divergence from the pan lineage (chimpanzees and bonobos). These findings demonstrate that human SLC22A10 is a unitary pseudogene and was inactivated by a missense mutation that is fixed in humans, whereas orthologs in great apes transport sex steroid conjugates

GLADX: An Automated Approach to Analyze the Lineage-Specific Loss and Pseudogenization of Genes

A well-established ancestral gene can usually be found, in one or multiple copies, in different descendant species. Sometimes during the course of evolution, all the representatives of a well-established ancestral gene disappear in specific lineages; such gene losses may occur in the genome by deletion of a DNA fragment or by pseudogenization. The loss of an entire gene family in a given lineage may reflect an important phenomenon, and could be due either to adaptation, or to a relaxation of selection that leads to neutral evolution. Therefore, the lineage-specific gene loss analyses are important to improve the understanding of the evolutionary history of genes and genomes. In order to perform this kind of study from the increasing number of complete genome sequences available, we developed a unique new software module called GLADX in the DAGOBAH framework, based on a comparative genomic approach. The software is able to automatically detect, for all the species of a phylum, the presence/absence of a representative of a well-established ancestral gene, and by systematic steps of re-annotation, confirm losses, detect and analyze pseudogenes and find novel genes. The approach is based on the use of highly reliable gene phylogenies, of protein predictions and on the analysis of genomic mutations. All the evidence associated to evolutionary approach provides accurate information for building an overall view of the evolution of a given gene in a selected phylum. The reliability of GLADX has been successfully tested on a benchmark analysis of 14 reported cases. It is the first tool that is able to fully automatically study the lineage-specific losses and pseudogenizations. GLADX is available at http://ioda.univ-provence.fr/IodaSite/gladx/

Étude du processus de perte de gènes et de pseudogénisation. Intégration et informatisation des concepts de l’évolution biologique. Application à la lignée humaine depuis l'origine des Eucaryotes

La biologie a connu une extraordinaire révolution avec l'arrivée de nombreux génomes entièrement séquencés. L'analyse de la quantité d'informations disponibles nécessite la création et l'utilisation d'outils informatiques automatisés. L'interprétation des données biologiques prend tout son sens à la lumière de l'évolution. En ce sens, les études évolutives sont incontestablement nécessaires pour donner un sens aux données biologiques. Dans ce contexte, le laboratoire développe des outils pour étudier l'évolution des génomes (et protéomes) à travers les mutations subies. Cette thèse porte sur l'étude spécifique des événements de pertes de gènes unitaires. Ces événements peuvent révéler des pertes de fonctions très instructives pour comprendre l'évolution des espèces. En premier lieu, j'ai développé l'outil GLADX qui mime l'expertise humaine afin d'étudier automatiquement et avec précision les événements de pertes de gènes unitaires. Ces études se basent sur la création et l'interprétation de données phylogénétiques, de BLAST, de prédictions protéiques, etc., dans un contexte automatisé. Ensuite, j'ai développé une stratégie utilisant l'outil GLADX pour étudier à grande échelle les pertes de gènes unitaires au cours de l'évolution du protéome humain. La stratégie utilise d'abord comme filtre l'analyse de groupes d'orthologues fabriqués par un outil de clustérisation à partir du protéome complet de nombreuses espèces. Cette analyse a permis de détecter 6237 pertes de gènes unitaires putatives dans la lignée humaine. L'étude approfondie de ces pertes avec GLADX a mis en évidence de nombreux problèmes liés à la qualité des données disponibles dans les bases de données.Biology has undergone an extraordinary revolution with the appearance of numerous whole genomes sequenced. Analysis of the amount of information available requires creation and use of automated tools. The interpretation of biological data becomes meaningful in light of evolution. In view of all this, evolutionary studies are undoubtedly necessary to highlight the biological data. In this context, the laboratory develops tools to study the genomes (and proteomes) evolution through all the undergone mutations. The project of this thesis focuses specifically on the events of unitary gene losses. These events may reveal loss of functions very instructive for understanding the evolution of species. First, I developed the GLADX tool that mimics human expertise to automatically and accurately investigate the events of unitary gene losses. These studies are based on the creation and interpretation of phylogenetic data, BLAST, predictions of protein, etc., in an automated environment. Secondly, I developed a strategy using GLADX tool to study, at large-scale, the loss of unitary genes during the evolution of the human proteome. The strategy uses, in the first step, the analysis of orthologous groups produced by a clustering tool from complete proteomes of numerous species. This analysis used as a filter, allowed detecting 6237 putative losses in the human lineage. The study of these unitary gene loss cases has been deepened with GLADX and allowed to highlight many problems with the quality of available data in databases

Methods to identify and study the evolution of pseudogenes using a phylogenetic approach

International audienceThe discovery that pseudogenes are involved in important biological processes has excited enthusiasm and increased the research interest on them. An accurate detection and analysis of pseudogenes can be achieved using comparative methods, but only the use of phylogenetic tools can provide accurate information about their birth, their evolution and their death, hence about the impact that they have on genes and genomes. Here, phylogenetic methods that allow for studying pseudogene history are described

NBISweden/EMBLmyGFF3: EMBLmyGFF3-1.2

change log: Modify installation of the tool. Could be installed/uninstalled using pip fix issue #1 => sorting the features to be sure they are sorted in increasing order of their locations, no matter their strand. Add python scripts to test the examples Some logs are now compressed by default for a better reading + Add the parameter --uncompressed_log to be able to have the log in its whole

EMBLmyGFF3: a converter facilitating genome annotation submission to European Nucleotide Archive

Abstract Objective The state-of-the-art genome annotation tools output GFF3 format files, while this format is not accepted as submission format by the International Nucleotide Sequence Database Collaboration (INSDC) databases. Converting the GFF3 format to a format accepted by one of the three INSDC databases is a key step in the achievement of genome annotation projects. However, the flexibility existing in the GFF3 format makes this conversion task difficult to perform. Until now, no converter is able to handle any GFF3 flavour regardless of source. Results Here we present EMBLmyGFF3, a robust universal converter from GFF3 format to EMBL format compatible with genome annotation submission to the European Nucleotide Archive. The tool uses json parameter files, which can be easily tuned by the user, allowing the mapping of corresponding vocabulary between the GFF3 format and the EMBL format. We demonstrate the conversion of GFF3 annotation files from four different commonly used annotation tools: Maker, Prokka, Augustus and Eugene. EMBLmyGFF3 is freely available at https://github.com/NBISweden/EMBLmyGFF3