Biomedical subjects

Didier Casane

Publications and source records attributed to Didier Casane.

12 recordsLinked to original sources

PubMed2026

Evidence of genome-wide relaxed selection on mildly deleterious mutations in an ancient subterranean catfish.

About one hundred subterranean catfish species have been described, resulting from repeated colonization of cave environments by multiple surface lineages. Most cave-dwelling species are found in the Americas, in particular in South America, but a few species also live in Central and North America. Despite the availability of high-quality genome assemblies for two cave species, the Mexican blind catfish Prietella phreatophila and the Colombian blind catfish Trichomycterus rosablanca, genomic approaches to investigate genetic changes associated with subterranean life or to estimate cave colonization times remain largely unexplored. To fill this gap, we additionally sequenced the genomes of four blind and depigmented subterranean catfishes from Peru (three Trichomycterus and one Astroblepus), as well as the genomes of four close surface relatives. We first extracted a large set of light-related genes, such as phototransduction and crystallin genes, and found contrasting decays of these sequences in different cave species, from 1% of pseudogenes in T. rosablanca to 48% in P. phreatophila. Two independent molecular dating methods gave congruent ages, indicating that these catfishes colonized subterranean habitats at different times, ranging from Early Pliocene to Late Pleistocene, supporting the hypothesis that surface catfishes repeatedly and rapidly adapted to subterranean habitats. The oldest cave species, P. phreatophila, appears to have been thriving in the dark for over 3.5 million years. Moreover, a genome-wide analysis of protein-coding genes suggests weaker purifying selection on mildly deleterious mutations in this cavefish than in other catfish lineages, likely reflecting a long-term small effective population size.

cavefishes↗

PubMed2006

Evidence of recombination in quasispecies populations of a Hepatitis C Virus patient undergoing anti-viral therapy.

BACKGROUND/AIM: Hepatitis C virus (HCV) has been the subject of intense research and clinical investigation as its major role in human disease has emerged. HCV circulates in vivo as a complex population of different but closely related viral variants, commonly referred to as a quasispecies. The extent to which recombination plays a role in the evolution of HCV quasispecies when patients are undergoing anti-viral therapy is currently unknown. In order to gain insight into these matters, we have performed a phylogenetic analysis of HCV quasispecies populations from six patients undergoing anti-viral therapy. METHODS: Putative recombinant sequences were identified with the use of SimPlot program. Recombination events were confirmed by bootscaning, using putative recombinant sequence as a query. Statistical support for the presence of a recombination event was done by the use of LARD program. RESULTS: A crossing-over event in the NS5A gene in a HCV strain recovered after four weeks of treatment was identified in quasispecies from a patient with sustained response. Putative parental-like strains were identified as strains circulating in previous weeks on the same patient. CONCLUSION: Only one recombinant strain was detected in all patient quasispecies populations studied. The recombination break-point is situated on the PKR-binding region of NS5A. Although recombination may not appeared to be extensive in NS5A genes of HCV quasispecies populations of patients undergoing antiviral therapy, this possibility should be taken into account as a mechanism of genetic variation for HCV.

Amino Acid Sequence↗

PubMed2006

An unusual choanoflagellate protein released by Hedgehog autocatalytic processing.

Hedgehog proteins are important cell-cell signalling proteins utilized during the development of multicellular animals. Members of the hedgehog gene family have not been detected outside the Metazoa, raising unanswered questions about their evolutionary origin. Here we report a highly unusual hedgehog-related gene from a choanoflagellate, a close unicellular relative of the animals. The deduced C-terminal domain, Hoglet-C, is homologous to the autocatalytic domain of Hedgehog proteins and is predicted to function in autocatalytic cleavage of the precursor peptide. In contrast, the N-terminal Hoglet-N peptide has no similarity to the signalling peptide of Hedgehog (Hh-N). Instead, Hoglet-N is deduced to be a secreted protein with an enormous threonine-rich domain of unprecedented size and purity (over 200 threonine residues) and two polysaccharide-binding domains. Structural modelling reveals that these domains have a novel combination of features found in cellulose-binding domains (CBD) of types IIa and IIb, and are expected to bind cellulose. We propose that the two CBD domains enable Hoglet-N to bind to plant matter, tethering an amorphous nucleophilic anchor, facilitating transient adhesion of the choanoflagellate cell. Since Hh-C and Hoglet-C are homologous, but Hh-N and Hoglet-N are not, we argue that metazoan hedgehog genes evolved by fusion of two distinct genes.

Amino Acid Sequence↗

PubMed2006

Morphological and gene expression similarities suggest that the ascidian neural gland may be osmoregulatory and homologous to vertebrate peri-ventricular organs.

Summary The central nervous system (cerebral ganglion) of adult ascidians is linked to the neural gland complex (NGC), which consists of a dorsal tubercle, a ciliated duct and a neural gland. The function of the NGC has been the subject of much debate. The recent publication of the complete genomic sequence of Ciona intestinalis provides new opportunities to examine the presence and distribution of protein families in this basal chordate. We focus here on the ascidian neuropeptide G-protein-coupled receptors (GPCRs), the vertebrate homologues of which are involved in homeostasis. In situ hybridization revealed that five Ciona GPCRs [vasopressin receptor, somatostatin receptor, CRH (corticotropin-releasing hormone) receptor, angiotensin receptor and tachykinin receptor] are expressed in the NGC of adult ascidians. These findings, together with histological and ultrastructural data, provide evidence to support a role for the ascidian NGC in maintaining ionic homeostasis. We further speculate about the potential similarities between the ascidian NGC and the vertebrate choroid plexus, a neural peri-ventricular organ.

Animals↗

PubMed2004

Phylogenomics of eukaryotes: impact of missing data on large alignments.

Resolving the relationships between Metazoa and other eukaryotic groups as well as between metazoan phyla is central to the understanding of the origin and evolution of animals. The current view is based on limited data sets, either a single gene with many species (e.g., ribosomal RNA) or many genes but with only a few species. Because a reliable phylogenetic inference simultaneously requires numerous genes and numerous species, we assembled a very large data set containing 129 orthologous proteins ( approximately 30,000 aligned amino acid positions) for 36 eukaryotic species. Included in the alignments are data from the choanoflagellate Monosiga ovata, obtained through the sequencing of about 1,000 cDNAs. We provide conclusive support for choanoflagellates as the closest relative of animals and for fungi as the second closest. The monophyly of Plantae and chromalveolates was recovered but without strong statistical support. Within animals, in contrast to the monophyly of Coelomata observed in several recent large-scale analyses, we recovered a paraphyletic Coelamata, with nematodes and platyhelminths nested within. To include a diverse sample of organisms, data from EST projects were used for several species, resulting in a large amount of missing data in our alignment (about 25%). By using different approaches, we verify that the inferred phylogeny is not sensitive to these missing data. Therefore, this large data set provides a reliable phylogenetic framework for studying eukaryotic and animal evolution and will be easily extendable when large amounts of sequence information become available from a broader taxonomic range.

Animals↗

PubMed2004

Evidence of intratypic recombination in natural populations of hepatitis C virus.

Hepatitis C virus (HCV) has high genomic variability and, since its discovery, at least six different types and an increasing number of subtypes have been reported. Genotype 1 is the most prevalent genotype found in South America. In the present study, three different genomic regions (5'UTR, core and NS5B) of four HCV strains isolated from Peruvian patients were sequenced in order to investigate the congruence of HCV genotyping for these three genomic regions. Phylogenetic analysis using 5'UTR-core sequences found strain PE22 to be related to subtype 1b. However, the same analysis using the NS5B region found it to be related to subtype 1a. To test the possibility of genetic recombination, phylogenetic studies were carried out, revealing that a crossover event had taken place in the NS5B protein. We discuss the consequences of this observation on HCV genotype classification, laboratory diagnosis and treatment of HCV infection.

5' Untranslated Regions↗

PubMed2003

Functional divergence prediction from evolutionary analysis: a case study of vertebrate hemoglobin.

It is a central assumption of evolution that gene duplications provide the genetic raw material from which to create proteins with new functions. The increasing availability in multigene family sequences that has resulted from genome projects has inspired the creation of novel in silico approaches to predict details of protein function. The underlying principle of all such approaches is to compare the evolutionary properties of homologous sequence positions in paralogous proteins. It has been proposed that the positions that show switches in substitution rate over time-i.e., "heterotachous sites," are good indicators of functional divergence. Here, we analyzed the alpha and beta paralogous subunits of hemoglobin in search for such signatures. We found as many heterotachous sites in comparisons between groups of paralogous subunits (alpha/beta) as between orthologous ones (alpha/alpha, beta/beta). Thus, the importance of substitution rate shifts as predictors of specialization between protein subfamilies might be reconsidered. Instead, such shifts may reflect a more general process of protein evolution, consistent with the fact that they can be compatible with function conservation. As an alternative, we focused on those residues showing highly constrained states in two sequence groups, but different in each group, and we named them CBD (for "constant but different"). As opposed to heterotachous positions, CBD sites were markedly overrepresented in paralogous (alpha/beta) comparisons, as opposed to orthologous ones (alpha/alpha, beta/beta), identifying them as likely signatures of functional specialization between the two subunits. When superimposed onto the three-dimensional structure of hemoglobin, CBD positions consistently appeared to cluster preferentially on inter-subunit surfaces, two contact areas crucial to function in vertebrate tetrameric hemoglobin. The identification and analysis of CBD sites by complementing structural information with evolutionary data may represent a promising direction for future studies dealing with the functional characterization of a growing number of multigene families identified by complete genome analyses.

Animals↗

PubMed2003

Evidence of recombination in natural populations of hepatitis A virus.

Genetic analysis of selected genome regions of hepatitis A virus (HAV) suggested that distinct genotypes of HAV could be found in different geographical regions. At least seven HAV genotypes have been identified all over the world, including four human genotypes (I, II, III, and VII) and three simian strains (IV, V, and VI). Phylogenetic analysis using full-length VP1 sequences revealed that human strain 9F94 has a close genetic relation with strain SLF-88 (sub-genotype VII). Nevertheless, the same analysis using full-length VP2 or VP3 sequences revealed that strain 9F94 has a close genetic relation with strain MBB (sub-genotype IB). To test the possibility of genetic recombination, phylogenetic studies were carried out, revealing that a crossing over had taken place in the VP1 capsid protein. These findings indicate that capsid-recombination can play a significant role in shaping the genetic diversity of HAV and, as such, can have important implications for its evolution, biology, and control.

Capsid Proteins↗

PubMed2002

Evolution of heteroplasmy at a mitochondrial tandem repeat locus in cultured rabbit cells.

Surveys of animal mitochondrial DNA (mtDNA) polymorphism reveal that mtDNA length variation is common. Much of this variation involves non-coding tandem repeat arrays in the main control region of the molecule. Despite a high mutation rate, generating systematic individual mtDNA length heteroplasmy, the number of repeats in a tandem array is maintained within a narrow range in lagomorphs. To investigate the basis for this apparent paradox, we studied the evolution of mtDNA length polymorphism in several rabbit cell clones containing different proportions of mtDNA, with four or five 153-bp repeats. Our data show that equivalent amounts of two mtDNA molecular types are not stable (evolution towards a predominant type being the rule) and that other types remain represented, maintaining the length polymorphism. The data suggest that mtDNA molecules with a longer array of repeats have a replicative advantage that could depend on the nuclear background.

Animals↗

PubMed2002

Molecular evolution of hepatitis A virus: a new classification based on the complete VP1 protein.

Hepatitis A virus (HAV) is a positive-stranded RNA virus in the genus Hepatovirus in the family Picornaviridae So far, analysis of the genetic variability of HAV has been based on two discrete regions, the VP1/2A junction and the VP1 N terminus. In this report, we determined the nucleotide and deduced amino acid sequences of the complete VP1 gene of 81 strains from France, Kosovo, Mexico, Argentina, Chile, and Uruguay and compared them with the sequences of seven strains of HAV isolated elsewhere. Overall strain variation in the complete VP1 gene was found to be as high as 23.7% at the nucleotide level and 10.5% at the amino acid level. Different phylogenetic methods revealed that HAV sequences form five distinct and well-supported genetic lineages. Within these lineages, HAV sequences clustered by geographical origin only for European strains. The analysis of the complete VP1 gene allowed insight into the mode of evolution of HAV and revealed the emergence of a novel variant with a 15-amino-acid deletion located on the VP1 region where neutralization escape mutations were found. This could be the first antigenic variant of HAV so far identified.

Amino Acid Sequence↗

PubMedDate not supplied

Comparison of even-skipped related gene expression pattern in vertebrates shows an association between expression domain loss and modification of selective constraints on sequences.

The even-skipped related genes (evx) encode homeodomain-containing transcription factors that play key roles in body patterning and neurogenesis in a wide array of Eumetazoa species. It is thought that the genome of the last common ancestor of Chordata contained a unique evx gene linked to a unique ancestral Hox complex. During subsequent evolution, two rounds of whole genome duplication followed by individual gene losses gave rise to three paralogs: evx1, evx2, and eve1. Then, eve1 was maintained in Actinopterygii lineage but not in Tetrapoda. To explain this discrepancy, we examined the expression patterns of the evx1 homologue, Xhox3, in Xenopus laevis and that of evx1 and eve1 in Danio rerio. We show here that Xhox3 is expressed in a manner that closely reflects the inferred expression pattern of the evx1 gene in the last common ancestor of Vertebrata (i.e., in gastrula, the central nervous system, the posterior gut, and the tip of the growing tail). Zebrafish evx1 and Xenopus Xhox3 are expressed in homologous cell lineages of the central nervous system and of the posterior gut, but evx1 was undetectable in the gastrula and the tail bud. Strikingly, eve1 is the only evx gene of zebrafish to be expressed in these two latter regions. Thus, the ancestral expression pattern of evx1 in vertebrates appears to have been distributed between evx1 and eve1 in zebrafish. We propose that evx1 and eve1 underwent a complementary loss of expression domain in zebrafish that allowed the maintenance of the two paralogs in accordance with the duplication-degeneration-complementation model. It is important to note that, in zebrafish, Evx1 and Eve1 have lost most of the protein domain upstream of the homeodomain. In addition, Eve1 has accumulated substitutions in positions that are highly conserved in all other Evx proteins. Thus, the reduction of the expression domain of both evx1 and eve1 in zebrafish appears to be associated with the modification of constraints on the protein sequences, allowing the shortening of both genes and an accelerated substitution rate in eve1.

Amino Acid Sequence↗

PubMedDate not supplied

Heterotachy and functional shift in protein evolution.

Study of structure/function relationships constitutes an important field of research, especially for modification of protein function and drug design. However, the fact that rational design (i.e. the modification of amino acid sequences by means of directed mutagenesis, based on knowledge of the three-dimensional structure) appears to be much less efficient than irrational design (i.e. random mutagenesis followed by in vitro selection) clearly indicates that we understand little about the relationships between primary sequence, three-dimensional structure and function. The use of evolutionary approaches and concepts will bring insights to this difficult question. The increasing availability of multigene family sequences that has resulted from genome projects has inspired the creation of novel in silico evolutionary methods to predict details of protein function in duplicated (paralogous) proteins. The underlying principle of all such approaches is to compare the evolutionary properties of homologous sequence positions in paralogs. It has been proposed that the positions that show switches in substitution rate over time--i.e., 'heterotachous sites'--are good indicators of functional divergence. However, it appears that heterotachy is a much more general process, since most variable sites of homologous proteins with no evidence of functional shift are heterotachous. Similarly, it appears that switches in substitution rate are as frequent when paralogous sequences are compared as when orthologous sequences are compared. Heterotachy, instead of being indicative of functional shift, may more generally reflect a less specific process related to the many intra- and inter-molecular interactions compatible with a range of more or less equally viable protein conformations. These interactions will lead to different constraints on the nature of the primary sequences, consistently with theories suggesting the non-independence of substitutions in proteins. However, a specific type of amino acid variation might constitute a good indicator of functional divergence: substitutions occurring at positions that are generally slowly evolving. Such substitutions at constrained sites are indeed much more frequent soon after gene duplication. The identification and analysis of these sites by complementing structural information with evolutionary data may represent a promising direction to future studies dealing with the functional characterization of an ever increasing number of multi-gene families identified by complete genome analysis.

Amino Acid Substitution↗