Genomic plasticity of the immune-related Mhc class I B region in macaque species

<p>Abstract</p> <p>Background</p> <p>In sharp contrast to humans and great apes, the expanded <it>Mhc</it>-<it>B </it>region of rhesus and cynomolgus macaques is characterized by the presence of differential numbers and unique combinations of polymorphic class I <it>B </it>genes per haplotype. The MIB microsatellite is closely linked to the single class I <it>B </it>gene in human and in some great apes studied. The physical map of the <it>Mhc </it>of a heterozygous rhesus monkey provides unique material to analyze MIB and <it>Mamu</it>-<it>B </it>copy number variation and then allows one to decipher the compound evolutionary history of this region in primate species.</p> <p>Results</p> <p><it>In silico </it>research pinpointed 12 MIB copies (duplicons), most of which are associated with expressed <it>B</it>-genes that cluster in a separate clade in the phylogenetic tree. Generic primers tested on homozygous rhesus and pedigreed cynomolgus macaques allowed the identification of eight to eleven MIB copies per individual. The number of MIB copies present per haplotype varies from a minimum of three to six in cynomolgus macaques and from five to eight copies in rhesus macaques. Phylogenetic analyses highlight a strong transpecific sharing of MIB duplicons. Using the physical map, we observed that, similar to MIB duplicons, highly divergent <it>Mamu</it>-<it>B </it>genes can be present on the same haplotype. Haplotype variation as reflected by the copy number variation of class I <it>B </it>loci is best explained by recombination events, which are found to occur between MIBs and <it>Mamu</it>-<it>B</it>.</p> <p>Conclusion</p> <p>The data suggest the existence of highly divergent MIB and <it>Mamu-B </it>lineages on a given haplotype, as well as variable MIB and <it>B </it>copy numbers and configurations, at least in rhesus macaque. Recombination seems to occur between MIB and <it>Mamu</it>-<it>B </it>loci, and the resulting haplotypic plasticity at the individual level may be a strategy to better cope with pathogens. Therefore, evolutionary inferences based on the multiplicated MIB loci but also other markers close to <it>B</it>-genes appear to be promising for the study of <it>B</it>-region organization and evolution in primates.</p

The Medicago truncatula GRAS protein RAD1 supports arbuscular mycorrhiza symbiosis and Phytophthora palmivora susceptibility.

The roots of most land plants are colonized by symbiotic arbuscular mycorrhiza (AM) fungi. To facilitate this symbiosis, plant genomes encode a set of genes required for microbial perception and accommodation. However, the extent to which infection by filamentous root pathogens also relies on some of these genes remains an open question. Here, we used genome-wide association mapping to identify genes contributing to colonization of Medicago truncatula roots by the pathogenic oomycete Phytophthora palmivora. Single-nucleotide polymorphism (SNP) markers most significantly associated with plant colonization response were identified upstream of RAD1, which encodes a GRAS transcription regulator first negatively implicated in root nodule symbiosis and recently identified as a positive regulator of AM symbiosis. RAD1 transcript levels are up-regulated both in response to AM fungus and, to a lower extent, in infected tissues by P. palmivora where its expression is restricted to root cortex cells proximal to pathogen hyphae. Reverse genetics showed that reduction of RAD1 transcript levels as well as a rad1 mutant are impaired in their full colonization by AM fungi as well as by P. palmivora. Thus, the importance of RAD1 extends beyond symbiotic interactions, suggesting a general involvement in M. truncatula microbe-induced root development and interactions with unrelated beneficial and detrimental filamentous microbes

Host-specific competitiveness to form nodules in Rhizobium leguminosarum symbiovar viciae

Fabeae legumes such as pea and faba bean form symbiotic nodules with a large diversity of soil Rhizobium leguminosarum symbiovar viciae (Rlv) bacteria. However, bacteria competitive to form root nodules (CFN) are generally not the most efficient to fix dinitrogen, resulting in a decrease in legume crop yields. Here, we investigate differential selection by host plants on the diversity of Rlv. A large collection of Rlv was collected by nodule trapping with pea and faba bean from soils at five European sites. Representative genomes were sequenced. In parallel, diversity and abundance of Rlv were estimated directly in these soils using metabarcoding. The CFN of isolates was measured with both legume hosts. Pea/faba bean CFN were associated to Rlv genomic regions. Variations of bacterial pea and/or faba bean CFN explained the differential abundance of Rlv genotypes in pea and faba bean nodules. No evidence was found for genetic association between CFN and variations in the core genome, but variations in specific regions of the nod locus, as well as in other plasmid loci, were associated with differences in CFN. These findings shed light on the genetic control of CFN in Rlv and emphasise the importance of host plants in controlling Rhizobium diversity

Compound Evolutionary History of the Rhesus Macaque Mhc Class I B Region Revealed by Microsatellite Analysis and Localization of Retroviral Sequences

In humans, the single polymorphic B locus of the major histocompatibility complex is linked to the microsatellite MIB. In rhesus macaques, however, haplotypes are characterized by the presence of unique combinations of multiple B genes, which may display different levels of polymorphism. The aim of the study was to shed light on the evolutionary history of this highly complex region. First, the robustness of the microsatellite MIB-linked to almost half of the B genes in rhesus macaques (Mamu-B)–for accurate B haplotyping was studied. Based on the physical map of an established haplotype comprising 7 MIB loci, each located next to a certain Mamu-B gene, two MIB loci, MIB1 and MIB6, were investigated in a panel of MHC homozygous monkeys. MIB1 revealed a complex genotyping pattern, whereas MIB6 analysis resulted in the detection of one or no amplicon. Both patterns are specific for a given B haplotype, show Mendelian segregation, and even allow a more precise haplotype definition than do traditional typing methods. Second, a search was performed for retroelements that may have played a role in duplication processes as observed in the macaque B region. This resulted in the description of two types of duplicons. One basic unit comprises an expressed Mamu-B gene, adjacent to an HERV16 copy closely linked to MIB. The second type of duplicon comprises a Mamu-B (pseudo)gene, linked to a truncated HERV16 structure lacking its MIB segment. Such truncation seems to coincide with the loss of B gene transcription. Subsequent to the duplication processes, recombination between MIB and Mamu-B loci appears to have occurred, resulting in a hyperplastic B region. Thus, analysis of MIB in addition to B loci allows deciphering of the compound evolutionary history of the class I B region in Old World monkeys

Processus démographiques et sélectifs expliquant les profils de diversité et de différenciation génétique des populations du macaque cynomolgus (Macaca fascicularis), espèce à vaste distribution discontinue

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A linkage disequilibrium-based statistical test for Genome-Wide Epistatic Selection Scans in structured populations

International audienceThe quest for signatures of selection using single nucleotide polymorphism (SNP) data has proven efficient to uncover genes involved in conserved and/or adaptive molecular functions, but none of the statistical methods were designed to identify interacting alleles as targets of selective processes. Here, we propose a statistical test aimed at detecting epistatic selection, based on a linkage disequilibrium (LD) measure accounting for population structure and heterogeneous relatedness between individuals. SNP-based (T-rv) and window-based (T-corPC1v) statistics fit a Student distribution, allowing to test the significance of correlation coefficients. As a proof of concept, we use SNP data from the Medicago truncatula symbiotic legume plant and uncover a previously unknown gene coadaptation between the MtSUNN (Super Numeric Nodule) receptor and the MtCLE02 (CLAVATA3-Like) signaling peptide. We also provide experimental evidence supporting a MtSUNN-dependent negative role of MtCLE02 in symbiotic root nodulation. Using human HGDP-CEPH SNP data, our new statistical test uncovers strong LD between SLC24A5 (skin pigmentation) and EDAR (hairs, teeth, sweat glands development) world-wide, which persists after correction for population structure and relatedness in Central South Asian populations. This result suggests that epistatic selection or coselection could have contributed to the phenotypic make-up in some human populations. Applying this approach to genome-wide SNP data will facilitate the identification of coadapted gene networks in model or non-model organisms

Besoins et ressentis des aidants en oncogériatrie, utilité d’un serious game

International audienceFaced with an ageing population, carers are real allies and partners who are essential to the smooth running of the care of elderly patients. The objective of this study was to analyse their needs in oncogeriatrics, in order to verify the relevance of developing a serious game to support them. Although the need for better support for carers in oncogeriatrics was recognized, they especially value the need for human exchanges