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Emmanuelle Lerat

Publications and source records attributed to Emmanuelle Lerat.

12 recordsLinked to original sources

Recognizing the pseudogenes in bacterial genomes.

Pseudogenes are now known to be a regular feature of bacterial genomes and are found in particularly high numbers within the genomes of recently emerged bacterial pathogens. As most pseudogenes are recognized by sequence alignments, we use newly available genomic sequences to identify the pseudogenes in 11 genomes from 4 bacterial genera, each of which contains at least 1 human pathogen. The numbers of pseudogenes range from 27 in Staphylococcus aureus MW2 to 337 in Yersinia pestis CO92 (e.g. 1-8% of the annotated genes in the genome). Most pseudogenes are formed by small frameshifting indels, but because stop codons are A + T-rich, the two low-G + C Gram-positive taxa (Streptococcus and Staphylococcus) have relatively high fractions of pseudogenes generated by nonsense mutations when compared with more G + C-rich genomes. Over half of the pseudogenes are produced from genes whose original functions were annotated as 'hypothetical' or 'unknown'; however, several broadly distributed genes involved in nucleotide processing, repair or replication have become pseudogenes in one of the sequenced Vibrio vulnificus genomes. Although many of our comparisons involved closely related strains with broadly overlapping gene inventories, each genome contains a largely unique set of pseudogenes, suggesting that pseudogenes are formed and eliminated relatively rapidly from most bacterial genomes.

Genome, Bacterial↗

Examining bacterial species under the specter of gene transfer and exchange.

Even in lieu of a dependable species concept for asexual organisms, the classification of bacteria into discrete taxonomic units is considered to be obstructed by the potential for lateral gene transfer (LGT) among lineages at virtually all phylogenetic levels. In most bacterial genomes, large proportions of genes are introduced by LGT, as indicated by their compositional features and/or phylogenetic distributions, and there is also clear evidence of LGT between very distantly related organisms. By adopting a whole-genome approach, which examined the history of every gene in numerous bacterial genomes, we show that LGT does not hamper phylogenetic reconstruction at many of the shallower taxonomic levels. Despite the high levels of gene acquisition, the only taxonomic group for which appreciable amounts of homologous recombination were detected was within bacterial species. Taken as a whole, the results derived from the analysis of complete gene inventories support several of the current means to recognize and define bacterial species.

Bacteria↗

Evolutionary origins of genomic repertoires in bacteria.

Explaining the diversity of gene repertoires has been a major problem in modern evolutionary biology. In eukaryotes, this diversity is believed to result mainly from gene duplication and loss, but in prokaryotes, lateral gene transfer (LGT) can also contribute substantially to genome contents. To determine the histories of gene inventories, we conducted an exhaustive analysis of gene phylogenies for all gene families in a widely sampled group, the gamma-Proteobacteria. We show that, although these bacterial genomes display striking differences in gene repertoires, most gene families having representatives in several species have congruent histories. Other than the few vast multigene families, gene duplication has contributed relatively little to the contents of these genomes; instead, LGT, over time, provides most of the diversity in genomic repertoires. Most such acquired genes are lost, but the majority of those that persist in genomes are transmitted strictly vertically. Although our analyses are limited to the gamma-Proteobacteria, these results resolve a long-standing paradox-i.e., the ability to make robust phylogenetic inferences in light of substantial LGT.

Bacteria↗

A bunch of fun-guys: the whole-genome view of yeast evolution.

The resolution of the complete sequences of several hemiascomycete genomes provides new insights into the ways that yeast genomes change in size and in gene contents. These genomes provide evidence of whole-genome duplication occurring before the divergence of Saccharomyces cerevisiae and Candida glabrata, followed by massive gene loss that restored diploidy. The pattern of genome evolution in yeast differs from that in bacteria apparently as a result of stronger selective constraints on bacterial chromosomes.

Candida glabrata↗

Psi-Phi: exploring the outer limits of bacterial pseudogenes.

Because bacterial chromosomes are tightly packed with genes and were traditionally viewed as being optimized for size and replication speed, it was not surprising that the early annotations of sequenced bacterial genomes reported few, if any, pseudogenes. But because pseudogenes are generally recognized by comparisons with their functional counterparts, as more genome sequences accumulated, many bacterial pathogens were found to harbor large numbers of truncated, inactivated, and degraded genes. Because the mutational events that inactivate genes occur continuously in all genomes, we investigated whether the rarity of pseudogenes in some bacteria was attributable to properties inherent to the organism or to the failure to recognize pseudogenes. By developing a program suite (called Psi-Phi, for Psi-gene Finder) that applies a comparative method to identify pseudogenes (attributable both to misannotation and to nonrecognition), we analyzed the pseudogene inventories in the sequenced members of the Escherichia coli/Shigella clade. This approach recovered hundreds of previously unrecognized pseudogenes and showed that pseudogenes are a regular feature of bacterial genomes, even in those whose original annotations registered no truncated or otherwise inactivated genes. In Shigella flexneri 2a, large proportions of pseudogenes are generated by nonsense mutations and IS element insertions, events that seldom produce the pseudogenes present in the other genomes examined. Almost all (>95%) pseudogenes are restricted to only one of the genomes and are of relatively recent origin, suggesting that these bacteria possess active mechanisms to eliminate nonfunctional genes.

Codon, Nonsense↗

The evolutionary history of quorum-sensing systems in bacteria.

Communication among bacterial cells through quorum-sensing (QS) systems is used to regulate ecologically and medically important traits, including virulence to hosts. QS is widespread in bacteria; it has been demonstrated experimentally in diverse phylogenetic groups, and homologs to the implicated genes have been discovered in a large proportion of sequenced bacterial genomes. The widespread distribution of the underlying gene families (LuxI/R and LuxS) raises the questions of how often QS genes have been transferred among bacterial lineages and the extent to which genes in the same QS system exchange partners or coevolve. Phylogenetic analyses of the relevant gene families show that the genes annotated as LuxI/R inducer and receptor elements comprise two families with virtually no homology between them and with one family restricted to the gamma-Proteobacteria and the other more widely distributed. Within bacterial phyla, trees for the LuxS and the two LuxI/R families show broad agreement with the ribosomal RNA tree, suggesting that these systems have been continually present during the evolution of groups such as the Proteobacteria and the Firmicutes. However, lateral transfer can be inferred for some genes (e.g., from Firmicutes to some distantly related lineages for LuxS). In general, the inducer/receptor elements in the LuxI/R systems have evolved together with little exchange of partners, although loss or replacement of partners has occurred in several lineages of gamma-Proteobacteria, the group for which sampling is most intensive in current databases. For instance, in Pseudomonas aeruginosa, a transferred QS system has been incorporated into the pathway of a native one. Gene phylogenies for the main LuxI/R family in Pseudomonas species imply a complex history of lateral transfer, ancestral duplication, and gene loss within the genus.

Bacteria↗

Hypervariable and highly divergent intron-exon organizations in the chordate Oikopleura dioica.

Oikopleura dioica is a pelagic tunicate with a very small genome and a very short life cycle. In order to investigate the intron-exon organizations in Oikopleura, we have isolated and characterized ribosomal protein EF-1alpha, Hox, and alpha-tubulin genes. Their intron positions have been compared with those of the same genes from various invertebrates and vertebrates, including four species with entirely sequenced genomes. Oikopleura genes, like Caenorhabditis genes, have introns at a large number of nonconserved positions, which must originate from late insertions or intron sliding of ancient insertions. Both species exhibit hypervariable intron-exon organization within their alpha-tubulin gene family. This is due to localization of most nonconserved intron positions in single members of this gene family. The hypervariability and divergence of intron positions in Oikopleura and Caenorhabditis may be related to the predominance of short introns, the processing of which is not very dependent upon the exonic environment compared to large introns. Also, both species have an undermethylated genome, and the control of methylation-induced point mutations imposes a control on exon size, at least in vertebrate genes. That introns placed at such variable positions in Oikopleura or C. elegans may serve a specific purpose is not easy to infer from our current knowledge and hypotheses on intron functions. We propose that new introns are retained in species with very short life cycles, because illegitimate exchanges including gene conversion are repressed. We also speculate that introns placed at gene-specific positions may contribute to suppressing these exchanges and thereby favor their own persistence.

Amino Acid Sequence↗

From gene trees to organismal phylogeny in prokaryotes: the case of the gamma-Proteobacteria.

The rapid increase in published genomic sequences for bacteria presents the first opportunity to reconstruct evolutionary events on the scale of entire genomes. However, extensive lateral gene transfer (LGT) may thwart this goal by preventing the establishment of organismal relationships based on individual gene phylogenies. The group for which cases of LGT are most frequently documented and for which the greatest density of complete genome sequences is available is the gamma-Proteobacteria, an ecologically diverse and ancient group including free-living species as well as pathogens and intracellular symbionts of plants and animals. We propose an approach to multigene phylogeny using complete genomes and apply it to the case of the gamma-Proteobacteria. We first applied stringent criteria to identify a set of likely gene orthologs and then tested the compatibilities of the resulting protein alignments with several phylogenetic hypotheses. Our results demonstrate phylogenetic concordance among virtually all (203 of 205) of the selected gene families, with each of the exceptions consistent with a single LGT event. The concatenated sequences of the concordant families yield a fully resolved phylogeny. This topology also received strong support in analyses aimed at excluding effects of heterogeneity in nucleotide base composition across lineages. Our analysis indicates that single-copy orthologous genes are resistant to horizontal transfer, even in ancient bacterial groups subject to high rates of LGT. This gene set can be identified and used to yield robust hypotheses for organismal phylogenies, thus establishing a foundation for reconstructing the evolutionary transitions, such as gene transfer, that underlie diversity in genome content and organization.

Bacteria↗

The source of laterally transferred genes in bacterial genomes.

BACKGROUND: Laterally transferred genes have often been identified on the basis of compositional features that distinguish them from ancestral genes in the genome. These genes are usually A+T-rich, arguing either that there is a bias towards acquiring genes from donor organisms having low G+C contents or that genes acquired from organisms of similar genomic base compositions go undetected in these analyses. RESULTS: By examining the genome contents of closely related, fully sequenced bacteria, we uncovered genes confined to a single genome and examined the sequence features of these acquired genes. The analysis shows that few transfer events are overlooked by compositional analyses. Most observed lateral gene transfers do not correspond to free exchange of regular genes among bacterial genomes, but more probably represent the constituents of phages or other selfish elements. CONCLUSIONS: Although bacteria tend to acquire large amounts of DNA, the origin of these genes remains obscure. We have shown that contrary to what is often supposed, their composition cannot be explained by a previous genomic context. In contrast, these genes fit the description of recently described genes in lambdoid phages, named 'morons'. Therefore, results from genome content and compositional approaches to detect lateral transfers should not be cited as evidence for genetic exchange between distantly related bacteria.

Arginine↗

Sequence divergence within transposable element families in the Drosophila melanogaster genome.

The availability of the sequenced Drosophila melanogaster genome provides an opportunity to study sequence variation between copies within transposable element families. In this study,we analyzed the 624 copies of 22 transposable element (TE) families (14 LTR retrotransposons, five non-LTR retrotransposons, and three transposons). LTR and non-LTR retrotransposons possessed far fewer divergent elements than the transposons,suggesting that the difference depends on the transposition mechanism. However,there was not a continuous range of divergence of the copies in each class,which were either very similar to the canonical elements,or very divergent from them. This sequence homogeneity among TE family copies matches the theoretical models of the dynamics of these repeated sequences. The sequenced Drosophila genome thus appears to be composed of a mixture of TEs that are still active and of ancient relics that have degenerated and the distribution of which along the chromosomes results from natural selection. This clearly demonstrates that the TEs are highly active within the genome,suggesting that the genetic variability of the Drosophila genome is still being renewed by the action of TEs.

Animals↗

Codon usage by transposable elements and their host genes in five species.

We compared the codon usage of sequences of transposable elements (TEs) with that of host genes from the species Drosophila melanogaster, Arabidopsis thaliana, Caenorhabditis elegans, Saccharomyces cerevisiae, and Homo sapiens. Factorial correspondence analysis showed that, regardless of the base composition of the genome, the TEs differed from the genes of their host species by their AT-richness. In all species, the percentage of A + T on the third codon position of the TEs was higher than that on the first codon position and lower than that in the noncoding DNA of the genomes. This indicates that the codon choice is not simply the outcome of mutational bias but is also subject to selection constraints. A tendency toward higher A + T on the third position than on the first position was also found in the host genes of A. thaliana, C. elegans, and S. cerevisiae but not in those of D. melanogaster and H. sapiens. This strongly suggests that the AT choice is a host-independent characteristic common to all TEs. The codon usage of TEs generally appeared to be different from the mean of the host genes. In the AT-rich genomes of Arabidopsis thaliana, Caenorhabditis elegans, and Saccharomyces cerevisiae, the codon usage bias of TEs was similar to that of weakly expressed genes. In the GC-rich genome of D. melanogaster, however, the bias in codon usage of the TEs clearly differed from that of weakly expressed genes. These findings suggest that selection acts on TEs and that TEs may display specific behavior within the host genomes.

Animals↗