Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: African Americans with head and neck squamous cell carcinoma (HNSCC) have a lower survival rate than whites. This study investigated the functional importance of ancestry-informative single-nucleotide polymorphisms (SNPs) in HNSCC and also examined the effect of functionally important genetic elements on racial disparities in HNSCC survival. METHODS: Ancestry-informative SNPs, RNA sequencing, methylation, and copy number variation data for 316 oral cavity and laryngeal cancer patients were analyzed across 178 DNA repair genes. The results of expression quantitative trait locus (eQTL) analyses were also replicated with a Gene Expression Omnibus (GEO) data set. The effects of eQTLs on overall survival (OS) and disease-free survival (DFS) were evaluated. RESULTS: Five ancestry-related SNPs were identified as cis-eQTLs in the DNA polymerase beta (POLB) gene (false discovery rate [FDR]<0.01). The homozygous/heterozygous genotypes containing the African allele showed higher POLB expression than the homozygous white allele genotype (P<.001). A replication study using a GEO data set validated all 5 eQTLs and also showed a statistically significant difference in POLB expression based on genetic ancestry (P=.002). An association was observed between these eQTLs and OS (P<.037; FDR<0.0363) as well as DFS (P=.018 to.0629; FDR<0.079) for oral cavity and laryngeal cancer patients treated with platinum-based chemotherapy and/or radiotherapy. Genotypes containing the African allele were associated with poor OS/DFS in comparison with homozygous genotypes harboring the white allele. CONCLUSIONS: Analyses show that ancestry-related alleles could act as eQTLs in HNSCC and support the association of ancestry-related genetic factors with survival disparities in patients diagnosed with oral cavity and laryngeal cancer. (C) 2016 American Cancer Society.
ISSN: 0008-543X

hal-01519253
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519253
DOI : 10.1002/cncr.30457
PUBMED : 27906459

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Prostate cancer disparities have been reported in men of African descent who show the highest incidence, mortality, compared with other ethnic groups. Few studies have explored the genetic and environmental factors for prostate cancer in men of African ancestry. The glutathione-S-transferases family conjugates carcinogens before their excretion and is expressed in prostate tissue. This study addressed the role of GSTM1 and GSTT1 deletions on prostate cancer risk in populations of African descent. This multi-institutional case-control study gathered data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database, the African-Caribbean Cancer Consortium (AC3) and Men of African Descent and Carcinoma of the Prostate Consortium (MADCaP). The analysis included 10 studies (1715 cases and 2363 controls), five in African-Americans, three in African-Caribbean and two in African men. Both the GSTM1 and the GSTT1 deletions showed significant inverse associations with prostate cancer [odds ratio (OR): 0.90, 95% confidence interval (CI) 0.83-0.97 and OR 0.88, 95% CI: 0.82-0.96, respectively]. The association was restricted to Caribbean and African populations. A significant positive association was observed between GSTM1 deletion and prostate cancer in smokers in African-American studies (OR: 1.28, 95% CI: 1.01-1.56), whereas a reduced risk was observed in never-smokers (OR: 0.66, 95% CI: 0.46-0.95). The risk of prostate cancer increased across quartiles of pack-years among subjects carrying the deletion of GSTM1 but not among subjects carrying a functional GSTM1. Gene-environment interaction between smoking and GSTM1 may be involved in the etiology of prostate cancer in populations of African descent.
ISSN: 0143-3334

hal-00682901
https://hal.archives-ouvertes.fr/hal-00682901
DOI : 10.1093/carcin/bgr119
PUBMED : 21705483

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
About 1-6% of the genetic ancestry of modern humans today originates from admixture with archaic humans. It has recently been shown that autosomal genomic regions with a reduced proportion of Neanderthal and Denisovan ancestries (NA and DA) are significantly enriched in genes that are more expressed in testis than in other tissues. To determine whether a cellular segregation pattern would exist, we combined maps of archaic introgression with a cross-analysis of three transcriptomic datasets deciphering the transcriptional landscape of human gonadal cell types. We reveal that the regions deficient in both NA and DA contain a significant enrichment of genes transcribed in meiotic germ cells. The interbreeding of anatomically modern humans with archaic humans may have introduced archaic-derived alleles that contributed to genetic incompatibilities affecting meiosis that were subsequently purged by natural selection.
ISSN: 0737-4038

hal-01578587
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578587
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578587/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578587/file/J%C3%A9gou%20et%20al%20-%20Meiotic%20Genes%20Are%20Enriched.pdf
DOI : 10.1093/molbev/msx141

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Ameloblastin (AMBN) is a phosphorylated, proline/glutamine-rich protein secreted during enamel formation. Previous studies have revealed that this enamel matrix protein was present early in vertebrate evolution and certainly plays important roles during enamel formation although its precise functions remain unclear. We performed evolutionary analyses of AMBN in order to (i) identify residues and motifs important for the protein function, (ii) predict mutations responsible for genetic diseases, and (iii) understand its molecular evolution in mammals. Results: In silico searches retrieved 56 complete sequences in public databases that were aligned and analyzed computationally. We showed that AMBN is globally evolving under moderate purifying selection in mammals and contains a strong phylogenetic signal. In addition, our analyses revealed codons evolving under significant positive selection. Evidence for positive selection acting on AMBN was observed in catarrhine primates and the aye-aye. We also found that (i) an additional translation initiation site was recruited in the ancestral placental AMBN, (ii) a short exon was duplicated several times in various species including catarrhine primates, and (iii) several polyadenylation sites are present. Conclusions: AMBN possesses many positions, which have been subjected to strong selective pressure for 200 million years. These positions correspond to several cleavage sites and hydroxylated, O-glycosylated, and phosphorylated residues. We predict that these conserved positions would be potentially responsible for enamel disorder if substituted. Some motifs that were previously identified as potentially important functionally were confirmed, and we found two, highly conserved, new motifs, the function of which should be tested in the near future. This study illustrates the power of evolutionary analyses for characterizing the functional constraints acting on proteins with yet uncharacterized structure.
ISSN: 1471-2148

Droits : http://creativecommons.org/licenses/by/
hal-01212816
http://hal.upmc.fr/hal-01212816
http://hal.upmc.fr/hal-01212816/document
http://hal.upmc.fr/hal-01212816/file/s12862-015-0431-0.pdf
DOI : 10.1186/s12862-015-0431-0

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Amelotin (AMTN) is an ameloblast-secreted protein that belongs to the secretory calcium-binding phosphoprotein family, which also includes the enamel matrix proteins amelogenin, ameloblastin and enamelin. Although AMTN is supposed to play an important role in enamel formation, data were long limited to the rodents, in which it is expressed during the maturation stage. Recent comparative studies in sauropsids and amphibians revealed that (i) AMTN was expressed earlier, i.e. as soon as ameloblasts are depositing the enamel matrix, and (ii) AMTN structure was different, a change which mostly resulted from an intraexonic splicing in the large exon 8 of an ancestral mammal. The present study was performed to know whether the differences in AMTN structure and expression in rodents compared to non-mammalian tetrapods dated back to an early ancestral mammal or were acquired later in mammalian evolution. We sequenced, assembled and screened the jaw transcriptome of a neonate opossum Monodelphis domestica, a marsupial. We found two AMTN transcripts. Variant 1, representing 70.8% of AMTN transcripts, displayed the structure known in rodents, whereas variant 2 (29.2%) exhibited the nonmammalian tetrapod structure. Then, we studied AMTN expression during amelogenesis in a neonate specimen. We obtained similar data as those reported in rodents. These findings indicate that more than 180 million years ago, before the divergence of marsupials and placentals, changes occurred in AMTN function and structure. The spatiotemporal expression was delayed to the maturation stage of amelogenesis and the intraexonic splicing gave rise to isoform 1, encoded by variant 1 and lacking the RGD motif. The ancestral isoform 2, housing the RGD, was initially conserved, as demonstrated here in a marsupial, then secondarily lost in the placental lineages. These findings bring new elements towards our understanding of the non-prismatic to prismatic enamel transition that occurred at the onset of mammals.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01233552
https://hal.archives-ouvertes.fr/hal-01233552
https://hal.archives-ouvertes.fr/hal-01233552/document
https://hal.archives-ouvertes.fr/hal-01233552/file/journal.pone.0133314.pdf
DOI : 10.1371/journal.pone.0133314

Éditeur(s) : Nature Publishing Group
Résumé : Vibrio nigripulchritudo is an emerging pathogen of farmed shrimp in New Caledonia and other regions in the Indo-Pacific. The molecular determinants of V. nigripulchritudo pathogenicity are unknown; however, molecular epidemiological studies have suggested that pathogenicity is linked to particular lineages. Here, we performed high-throughput sequencing-based comparative genome analysis of 16 V. nigripulchritudo strains to explore the genomic diversity and evolutionary history of pathogen-containing lineages and to identify pathogen-specific genetic elements. Our phylogenetic analysis revealed three pathogen-containing V. nigripulchritudo clades, including two clades previously identified from New Caledonia and one novel clade comprising putatively pathogenic isolates from septicemic shrimp in Madagascar. The similar genetic distance between the three clades indicates that they have diverged from an ancestral population roughly at the same time and recombination analysis indicates that these genomes have, in the past, shared a common gene pool and exchanged genes. As each contemporary lineage is comprised of nearly identical strains, comparative genomics allowed differentiation of genetic elements specific to shrimp pathogenesis of varying severity. Notably, only a large plasmid present in all highly pathogenic (HP) strains encodes a toxin. Although less/non-pathogenic strains contain related plasmids, these are differentiated by a putative toxin locus. Expression of this gene by a non-pathogenic V. nigripulchritudo strain resulted in production of toxic culture supernatant, normally an exclusive feature of HP strains. Thus, this protein, here termed 'nigritoxin', is implicated to an extent that remains to be precisely determined in the toxicity of V. nigripulchritudo.
Isme Journal (1751-7362) (Nature Publishing Group), 2013-10 , Vol. 7 , N. 10 , P. 1985-1996

Droits : 2013 International Society for Microbial Ecology All rights reserved 1751-7362/13
http://archimer.ifremer.fr/doc/00160/27117/28369.pdf
DOI:10.1038/ismej.2013.90
http://archimer.ifremer.fr/doc/00160/27117/

Éditeur(s) : Public Library Science
Résumé : Background: Reconstructing the history of divergence and gene flow between closely-related organisms has long been a difficult task of evolutionary genetics. Recently, new approaches based on the coalescence theory have been developed to test the existence of gene flow during the process of divergence. The deep sea is a motivating place to apply these new approaches. Differentiation by adaptation can be driven by the heterogeneity of the hydrothermal environment while populations should not have been strongly perturbed by climatic oscillations, the main cause of geographic isolation at the surface. Methodology/Principal Finding: Samples of DNA sequences were obtained for seven nuclear loci and a mitochondrial locus in order to conduct a multi-locus analysis of divergence and gene flow between two closely related and hybridizing species of hydrothermal vent mussels, Bathymodiolus azoricus and B. puteoserpentis. The analysis revealed that (i) the two species have started to diverge approximately 0.760 million years ago, (ii) the B. azoricus population size was 2 to 5 time greater than the B. puteoserpentis and the ancestral population and (iii) gene flow between the two species occurred over the complete species range and was mainly asymmetric, at least for the chromosomal regions studied. Conclusions/Significance: A long history of gene flow has been detected between the two Bathymodiolus species. However, it proved very difficult to conclusively distinguish secondary introgression from ongoing parapatric differentiation. As powerful as coalescence approaches could be, we are left by the fact that natural populations often deviates from standard assumptions of the underlying model. A more direct observation of the history of recombination at one of the seven loci studied suggests an initial period of allopatric differentiation during which recombination was blocked between lineages. Even in the deep sea, geographic isolation may well be a crucial promoter of speciation.
Plos One (1932-6203) (Public Library Science), 2009-08 , Vol. 4 , N. 8 , P. 1-15

Droits : 2009 Faure et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
http://archimer.ifremer.fr/doc/00129/24012/21972.pdf
DOI:10.1371/journal.pone.0006485
http://archimer.ifremer.fr/doc/00129/24012/

Éditeur(s) : Elsevier
Résumé : Correlation between DNA microsatellite heterozygosity and growth rate was investigated in two hatchery-propagated stocks of the shrimp Penaeus stylirostris, which had been genetically isolated from wild founders for 17 generations, and from each other for five more generations. presumed demographic history of these populations suggested that they were maintained at small effective population sizes. and this was confirmed by significant changes in allelic frequencies between the two stocks. Despite a small sample size (n = 60) and a small number of loci screened, a significant positive correlation was detected between microsatellite tri-locus heterozygosity and growth rate in one of the two stocks (r = 0.3, P = 0.02). In the other stock (n = 48), the positive correlation was not significant, but the combined test of single locus heterozygote advantage over the three loci was significant (P = 0.005).Use of DNA microsatellite markers, whose selectively neutral status is generally accepted, allowed us to reject the hypothesis of direct overdominance at marker loci as an explanation for an association of growth rate with heterozygosity. The average depression associated with one locus in our case is above or equivalent to the amount observed for a 10% increase of inbreeding in other species. These results suggest that heterozygosity at neutral marker loci is sufficiently well correlated with individual inbreeding coefficients to reveal a significant residual inbreeding load for growth rate in Tahitian P. stylirostris stocks. Inbreeding during hatchery propagation was, thus, insufficient to purge the ancestral load.
Aquaculture (0044-8486) (Elsevier), 2000-04 , Vol. 184 , N. 3-4 , P. 203-219

Droits : 2000 Elsevier Science B.V. All rights reserved
http://archimer.ifremer.fr/doc/2000/publication-753.pdf
DOI:10.1016/S0044-8486(99)00331-2
http://archimer.ifremer.fr/doc/00000/753/

Éditeur(s) : HAL CCSD National Academy of Sciences
Résumé : International audience
The complexity and depth of the relationships between the three domains of life challenge the reliability of phylogenetic methods, encouraging the use of alternative analytical tools. We reconstructed a gene similarity network comprising the proteomes of 14 eukaryotes, 104 prokaryotes, 2,389 viruses and 1,044 plasmids. This network contains multiple signatures of the chimerical origin of Eukaryotes as a fusion of an archaebacterium and a eubacterium that could not have been observed using phylogenetic trees. A number of connected components (gene sets with stronger similarities than expected by chance) contain pairs of eukaryotic sequences exhibiting no direct detectable similarity. Instead, many eukaryotic sequences were indirectly connected through a ``eukaryote-archaebacterium-eubacterium-eukaryote'' similarity path. Furthermore, eukaryotic genes highly connected to prokaryotic genes from one domain tend not to be connected to genes from the other prokaryotic domain. Genes of archaebacterial and eubacterial ancestry tend to perform different functions and to act at different subcellular compartments, but in such an intertwined way that suggests an early rather than late integration of both gene repertoires. The archaebacterial repertoire has a similar size in all eukaryotic genomes whereas the number of eubacterium-derived genes is much more variable, suggesting a higher plasticity of this gene repertoire. Consequently, highly reduced eukaryotic genomes contain more genes of archaebacterial than eubacterial affinity. Connected componentswith prokaryotic and eukaryotic genes tend to include viral and plasmid genes, compatible with a role of gene mobility in the origin of Eukaryotes. Our analyses highlight the power of network approaches to study deep evolutionary events.
ISSN: 0027-8424

hal-01544798
https://hal.archives-ouvertes.fr/hal-01544798
DOI : 10.1073/pnas.1211371110

Éditeur(s) : HAL CCSD Medknow Publications
Résumé : International audience
Multiple regions of the genome have been associated with the risk of prostate cancer in Caucasians, particularly including several polymorphisms located at 8q24. Region 2 of 8q24 has been repeatedly found to be associated with the risk of prostate cancer among men of African descent, although one study performed in the Caribbean island of Jamaica did not report this finding. In this study, the single nucleotide polymorphism rs16901979, located in region 2 of 8q24, was genotyped in 498 cases of histologically confirmed prostate cancer and 541 controls from the French Caribbean islands of Guadeloupe, where the population is largely of African descent. The AA genotype and the A allele at rs16901979 were associated with elevated risks of prostate cancer (odds ratios [ORs] = 1.84, 95% confidence interval [95% CI] = 1.26-2.69, P = 0.002 and OR = 1.36, 95% CI = 1.13-1.64, P = 0.001, respectively). Following stratification of the patients by disease aggressiveness, as defined by the Gleason score, the pooled genotypes AC + AA were associated with a higher risk of a Gleason score ≥7 at diagnosis (OR = 1.79, 95% CI = 1.17-2.73, P = 0.007). In summary, the A allele at rs16901979 was associated with the risk of prostate cancer in the Caribbean population of Guadeloupe, confirming its involvement in populations of African descent. Moreover, our study provides the first evidence of an association between this variant and the risk of aggressive prostate cancer.
ISSN: 1008-682X

Droits : http://creativecommons.org/licenses/by-nc-sa/
hal-01118552
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118552
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118552/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118552/file/AsianJAndrol171117-1705456_044414.pdf
DOI : 10.4103/1008-682X.135127

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The common endosymbiotic Wolbachia bacteria influence arthropod hosts in multiple ways. They are mostly recognized for their manipulations of host reproduction, yet, more recent studies demonstrate that Wolbachia also impact host behavior, metabolic pathways and immunity. Besides their biological and evolutionary roles Wolbachia are new potential biological control agents for pest and vector management. Importantly, Wolbachia-based control strategies require controlled symbiont transfer between host species and predictable outcomes of novel Wolbachia-host associations. Theoretically, this artificial horizontal transfer could inflict genetic changes within transferred Wolbachia populations. This could be facilitated through de novo mutations in the novel recipient host or changes of haplotype frequencies of polymorphic Wolbachia populations when transferred from donor to recipient hosts. Here we show that Wolbachia resident in the European cherry fruit fly, Rhagoletis cerasi, exhibit ancestral and cryptic sequence polymorphism in three symbiont genes, which are exposed upon microinjection into the new hosts Drosophila simulans and Ceratitis capitata. Our analyses of Wolbachia in microinjected D. simulans over 150 generations after microinjection uncovered infections with multiple Wolbachia strains in trans-infected lines that had previously been typed as single infections. This confirms the persistence of low-titer Wolbachia strains in microinjection experiments that had previously escaped standard detection techniques. Our study demonstrates that infections by multiple Wolbachia strains can shift in prevalence after artificial host transfer driven by either stochastic or selective processes. Trans-infection of Wolbachia can claim fitness costs in new hosts and we speculate that these costs may have driven the shifts of Wolbachia strains that we saw in our model system.
ISSN: 1932-6203

hal-01544765
https://hal.archives-ouvertes.fr/hal-01544765
DOI : 10.1371/journal.pone.0082402

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Standard microbial evolutionary ontology is organized according to a nested hierarchy of entities at various levels of biological organization. It typically detects and defines these entities in relation to the most stable aspects of evolutionary processes, by identifying lineages evolving by a process of vertical inheritance from an ancestral entity. However, recent advances in microbiology indicate that such an ontology has important limitations. The various dynamics detected within microbiological systems reveal that a focus on the most stable entities (or features of entities) over time inevitably underestimates the extent and nature of microbial diversity. These dynamics are not the outcome of the process of vertical descent alone. Other processes, often involving causal interactions between entities from distinct levels of biological organisation, or operating at different time scales, are responsible not only for the destabilisation of pre-existing entities, but also for the emergence and stabilisation of novel entities in the microbial world. In this article we consider microbial entities as more or less stabilised functional wholes, and sketch a network-based ontology that can represent a diverse set of processes including, for example, as well as phylogenetic relations, interactions that stabilise or destabilise the interacting entities, spatial relations, ecological connections, and genetic exchanges. We use this pluralistic framework for evaluating (i) the existing ontological assumptions in evolution (e.g. whether currently recognized entities are adequate for understanding the causes of change and stabilisation in the microbial world), and (ii) for identifying hidden ontological kinds, essentially invisible from within a more limited perspective. We propose to recognize additional classes of entities that provide new insights into the structure of the microbial world, namely ``processually equivalent'' entities, ``processually versatile'' entities, and ``stabilized'' entities.
ISSN: 0169-3867

hal-01544796
https://hal.archives-ouvertes.fr/hal-01544796
DOI : 10.1007/s10539-012-9350-2

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Deciphering the evolutionary processes driving nucleotide variation in multiallelic genes is limited by the number of genetic systems in which such genes occur. The complementary sex determiner (csd) gene in the honey bee Apis mellifera is an informative example for studying allelic diversity and the underlying evolutionary forces in a well-described model of balancing selection. Acting as the primary signal of sex determination, diploid individuals heterozygous for csd develop into females, whereas csd homozygotes are diploid males that have zero fitness. Examining 77 of the functional heterozygous csd allele pairs, we established a combinatorical criteria that provide insights into the minimum number of amino acid differences among those pairs. Given a data set of 244 csd sequences, we show that the total number of csd alleles found in A. mellifera ranges from 53 (locally) to 87 (worldwide), which is much higher than was previously reported (20). Using a coupon-collector model, we extrapolate the presence of in total 116-145 csd alleles worldwide. The hypervariable region (HVR) is of particular importance in determining csd allele specificity, and we provide for this region evidence of high evolutionary rate for length differences exceeding those of microsatellites. The proportion of amino acids driven by positive selection and the rate of nonsynonymous substitutions in the HVR-flanking regions reach values close to 1 but differ with respect to the HVR length. Using a model of csd coalescence, we identified the high originating rate of csd specificities as a major evolutionary force, leading to an origin of a novel csd allele every 400,000 years. The csd polymorphism frequencies in natural populations indicate an excess of new mutations, whereas signs of ancestral transspecies polymorphism can still be detected. This study provides a comprehensive view of the enormous diversity and the evolutionary forces shaping a multiallelic gene.
ISSN: 0737-4038

hal-01544758
https://hal.archives-ouvertes.fr/hal-01544758
DOI : 10.1093/molbev/mst207