Biomedical subjects

Ingrid Lafontaine

Publications and source records attributed to Ingrid Lafontaine.

6 recordsLinked to original sources

PubMed2006

The RNA polymerase III-dependent family of genes in hemiascomycetes: comparative RNomics, decoding strategies, transcription and evolutionary implications.

We present the first comprehensive analysis of RNA polymerase III (Pol III) transcribed genes in ten yeast genomes. This set includes all tRNA genes (tDNA) and genes coding for SNR6 (U6), SNR52, SCR1 and RPR1 RNA in the nine hemiascomycetes Saccharomyces cerevisiae, Saccharomyces castellii, Candida glabrata, Kluyveromyces waltii, Kluyveromyces lactis, Eremothecium gossypii, Debaryomyces hansenii, Candida albicans, Yarrowia lipolytica and the archiascomycete Schizosaccharomyces pombe. We systematically analysed sequence specificities of tRNA genes, polymorphism, variability of introns, gene redundancy and gene clustering. Analysis of decoding strategies showed that yeasts close to S.cerevisiae use bacterial decoding rules to read the Leu CUN and Arg CGN codons, in contrast to all other known Eukaryotes. In D.hansenii and C.albicans, we identified a novel tDNA-Leu (AAG), reading the Leu CUU/CUC/CUA codons with an unusual G at position 32. A systematic 'p-distance tree' using the 60 variable positions of the tRNA molecule revealed that most tDNAs cluster into amino acid-specific sub-trees, suggesting that, within hemiascomycetes, orthologous tDNAs are more closely related than paralogs. We finally determined the bipartite A- and B-box sequences recognized by TFIIIC. These minimal sequences are nearly conserved throughout hemiascomycetes and were satisfactorily retrieved at appropriate locations in other Pol III genes.

Ascomycota↗

PubMed2005

Comparative genomics of hemiascomycete yeasts: genes involved in DNA replication, repair, and recombination.

Among genes conserved from bacteria to mammals are those involved in replicating and repairing DNA. Following the complete sequencing of four hemiascomycetous yeast species during the course of the Genolevures 2 project, we have studied the conservation of 106 genes involved in replication, repair, and recombination in Candida glabrata, Kluyveromyces lactis, Debaryomyces hansenii, and Yarrowia lipolytica and compared them with their Saccharomyces cerevisiae orthologues. We found that proteins belonging to the replication fork and to the nucleotide excision repair pathway were-on the average-more conserved than proteins involved in the checkpoint response to DNA damage or in meiotic recombination. The meiotic recombination proteins Spo11p and Mre11p-Rad50p, involved in making meiotic double-strand breaks (DSBs), are conserved as is Mus81p, involved in resolving meiotic recombination intermediates. Interestingly, genes found in organisms in which DSB-repair is required for proper synapsis during meiosis are also found in C. glabrata, K. lactis, and D. hansenii but not in Y. lipolytica, suggesting that two modes of meiotic recombination have been selected during evolution of the hemiascomycetous yeasts. In addition, we found that SGS1 and TOP1, respectively, a DEAD/DEAH helicase and a type I topoisomerase, are duplicated in C. glabrata and that SRS2, a helicase involved in homologous recombination, is tandemly duplicated in K. lactis. Phylogenetic analyses show that the duplicated SGS1 gene evolved faster than the original gene, probably leading to a specialization of function of the duplicated copy.

Amino Acid Sequence↗

PubMed2004

Comparative genomics in hemiascomycete yeasts: evolution of sex, silencing, and subtelomeres.

The recent release of sequences of several unexplored yeast species that cover an evolutionary range comparable to the entire phylum of chordates offers us a unique opportunity to investigate how genes involved in adaptation have been shaped by evolution. We have examined how three different sets of genes, all related to adaptative processes at the genomic level, have evolved in hemiascomycetes: (1) the mating-type genes that govern sexuality, (2) the silencing genes that are connected to regulation of mating-type cassettes and to telomere position effect, and (3) the gene families found repeated in subtelomeric regions. We report new combinations of mating-type genes and cassettes in hemiascomycetous species; we show that silencing proteins diverge rapidly. We have also found that in all species studied, subtelomeric gene families exist and are specific to each species.

Amino Acid Sequence↗

PubMed2004

Large-scale exploration of growth inhibition caused by overexpression of genomic fragments in Saccharomyces cerevisiae.

We have screened the genome of Saccharomyces cerevisiae for fragments that confer a growth-retardation phenotype when overexpressed in a multicopy plasmid with a tetracycline-regulatable (Tet-off) promoter. We selected 714 such fragments with a mean size of 700 base-pairs out of around 84,000 clones tested. These include 493 in-frame open reading frame fragments corresponding to 454 distinct genes (of which 91 are of unknown function), and 162 out-of-frame, antisense and intergenic genomic fragments, representing the largest collection of toxic inserts published so far in yeast.

Cloning, Molecular↗

PubMed2004

Genome evolution in yeasts.

Identifying the mechanisms of eukaryotic genome evolution by comparative genomics is often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. The hemiascomycete yeasts, with their compact genomes, similar lifestyle and distinct sexual and physiological properties, provide a unique opportunity to explore such mechanisms. We present here the complete, assembled genome sequences of four yeast species, selected to represent a broad evolutionary range within a single eukaryotic phylum, that after analysis proved to be molecularly as diverse as the entire phylum of chordates. A total of approximately 24,200 novel genes were identified, the translation products of which were classified together with Saccharomyces cerevisiae proteins into about 4,700 families, forming the basis for interspecific comparisons. Analysis of chromosome maps and genome redundancies reveal that the different yeast lineages have evolved through a marked interplay between several distinct molecular mechanisms, including tandem gene repeat formation, segmental duplication, a massive genome duplication and extensive gene loss.

Chromosomes, Fungal↗

PubMed2004

Gene relics in the genome of the yeast Saccharomyces cerevisiae.

There is increasing evidence that DNA duplication is a common and ongoing process that plays a major role in molecular evolution of genomes and that a large fraction of the duplicated gene copies becomes non-functional by accumulation of deleterious mutations. In order to describe this phenomenon, we systematically searched the 6404 intergenic regions (IRs) of the genome of Saccharomyces cerevisiae for traces of coding sequences presenting degenerated but still recognizable sequence similarity with active open reading frames (5823 annotated ORFs). We detected a total of 124 anciently coding regions, or "gene relics", showing similarity to a total of 149 distinct active ORFs. This set of relics shows a continuum of sequence degeneration from those whose sequence is slightly altered compared to the functional ORF (classically defined as pseudogenes), to those that contains so many deleterious mutations, as to reach the limit of recognition. Gene relics are more concentrated in the subtelomeric regions of the chromosomes, reflecting the high plasticity of these regions. The presence of relics also revealed ancestral duplication events of chromosomal segments that were previously undetected. Some of these segments are intermingled with the more easily recognizable ancestral blocks of duplication, indicating successive duplication events. We present a compilation of all the data available, leading to a total of 278 pseudogenes in the genome of S. cerevisiae.

Chromosomes, Fungal↗