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Anthony W De Tomaso – 1st expert on this subject based on the ideXlab platform

  • Balancing selection on Allorecognition genes in the colonial ascidian Botryllus schlosseri.
    Developmental and Comparative Immunology, 2016
    Co-Authors: Marie L. Nydam, Emily E. Stephenson, Claire E. Waldman, Anthony W De Tomaso


    Abstract Allorecognition is the capability of an organism to recognize its own or related tissues. The colonial ascidian Botryllus schlosseri , which comprises five genetically distinct and divergent species (Clades A-E), contains two adjacent genes that control Allorecognition: fuhc sec and fuhc tm . These genes have been characterized extensively in Clade A and are highly polymorphic. Using alleles from 10 populations across the range of Clade A, we investigated the type and strength of selection maintaining this variation. Both fuhc genes exhibit higher within-population variation and lower population differentiation measures (F ST ) than neutral loci. The fuhc genes contain a substantial number of codons with >95% posterior probability of d N /d S  > 1. fuhc sec and fuhc tm also have polymorphisms shared between Clade A and Clade E that were present prior to speciation (trans-species polymorphisms). These results provide robust evidence that the fuhc genes are evolving under balancing selection.

  • Molecular evolution and in vitro characterization of Botryllus histocompatibility factor
    Immunogenetics, 2015
    Co-Authors: Daryl A Taketa, Marie L. Nydam, Adam D. Langenbacher, Delany Rodriguez, Erin Sanders, Anthony W De Tomaso


    Botryllus schlosseri is a colonial ascidian with a natural ability to anastomose with another colony to form a vascular and hematopoietic chimera. In order to fuse, two individuals must share at least one allele at the highly polymorphic fuhc locus. Otherwise, a blood-based inflammatory response will occur resulting in a melanin scar at the sites of interaction. The single-locus genetic control of Allorecognition makes B. schlosseri an attractive model to study the underlying molecular mechanisms. Over the past decade, several candidate genes involved in Allorecognition have been identified, but how they ultimately contribute to Allorecognition outcome remains poorly understood. Here, we report our initial molecular characterization of a recently identified candidate allodeterminant called Botryllus histocompatibility factor ( bhf ). bhf , both on a DNA and protein level, is the least polymorphic protein in the fuhc locus studied so far and, unlike other known Allorecognition determinants, does not appear to be under any form of balancing or directional selection. Additionally, we identified a second isoform through mRNA-Seq and an EST assembly library which is missing exon 3, resulting in a C-terminally truncated form. We report via whole-mount fluorescent in situ hybridization that a subset of cells co-express bhf and cfuhc ^ sec . Finally, we observed BHF’s localization in HEK293T at the cytoplasmic side of the plasma membrane in addition to the nucleus via a nuclear localization signal. Given the localization data thus far, we hypothesize that BHF may function as a scaffolding protein in a complex with other Botryllus proteins, rather than functioning as an Allorecognition determinant.

  • botryllus schlosseri Allorecognition tackling the enigma
    Developmental and Comparative Immunology, 2015
    Co-Authors: Daryl A Taketa, Anthony W De Tomaso


    Allorecognition has been well-studied in the context of vertebrate adaptive immunity and recognition of the Major Histocompatibility Complex (MHC), which is the central event of vertebrate immune responses. Although Allorecognition systems have been identified throughout the metazoa, recent results have shown that there is no apparent conservation or orthologous relationship between the mechanisms underlying this phenomenon in different organisms. Thus the origin of the vertebrate adaptive immune system as well as these other complex recognition systems is a complete mystery. This review will focus on Allorecognition in Botryllus schlosseri, a basal chordate which undergoes a natural transplantation reaction following contact between two individuals, and, analogous to vertebrates, is controlled by a single locus. We will summarize each of the known candidate genes within this locus and their potential roles in Allorecognition, and speculate on how these findings may in fact be revealing potential functional relationships between disparate Allorecognition systems.

Louise N Glass – 2nd expert on this subject based on the ideXlab platform

  • programmed cell death in neurospora crassa is controlled by the Allorecognition determinant rcd 1
    Genetics, 2019
    Co-Authors: Asen Daskalov, Louise N Glass, Pierre Gladieux, Jens Heller


    Nonself recognition following cell fusion between genetically distinct individuals of the same species in filamentous fungi often results in a programmed cell death (PCD) reaction, where the heterokaryotic fusion cell is compartmentalized and rapidly killed. The Allorecognition process plays a key role as a defense mechanism that restricts genome exploitation, resource plundering, and the spread of deleterious senescence plasmids and mycoviruses. Although a number of incompatibility systems have been described that function in mature hyphae, less is known about the PCD pathways in asexual spores, which represent the main infectious unit in various human and plant fungal pathogens. Here, we report the identification of regulator of cell death-1 (rcd-1), a novel Allorecognition gene, controlling PCD in germinating asexual spores of Neurospora crassa; rcd-1 is one of the most polymorphic genes in the genomes of wild N. crassa isolates. The coexpression of two antagonistic rcd-1-1 and rcd-1-2 alleles was necessary and sufficient to trigger cell death in fused germlings and in hyphae. Based on analysis of wild populations of N. crassa and N. discreta, rcd-1 alleles appeared to be under balancing selection and associated with trans-species polymorphisms. We shed light on genomic rearrangements that could have led to the emergence of the incompatibility system in Neurospora and show that rcd-1 belongs to a much larger gene family in fungi. Overall, our work contributes toward a better understanding of Allorecognition and PCD in an underexplored developmental stage of filamentous fungi.

  • nlr surveillance of essential sec 9 snare proteins induces programmed cell death upon Allorecognition in filamentous fungi
    Proceedings of the National Academy of Sciences of the United States of America, 2018
    Co-Authors: Louise N Glass, Pierre Gladieux, Jens Heller, Corinne Clave, Sven J Saupe


    In plants and metazoans, intracellular receptors that belong to the NOD-like receptor (NLR) family are major contributors to innate immunity. Filamentous fungal genomes contain large repertoires of genes encoding for proteins with similar architecture to plant and animal NLRs with mostly unknown function. Here, we identify and molecularly characterize patatin-like phospholipase-1 (PLP-1), an NLR-like protein containing an N-terminal patatin-like phospholipase domain, a nucleotide-binding domain (NBD), and a C-terminal tetratricopeptide repeat (TPR) domain. PLP-1 guards the essential SNARE protein SEC-9; genetic differences at plp-1 and sec-9 function to trigger Allorecognition and cell death in two distantly related fungal species, Neurospora crassa and Podospora anserina Analyses of Neurospora population samples revealed that plp-1 and sec-9 alleles are highly polymorphic, segregate into discrete haplotypes, and show transspecies polymorphism. Upon fusion between cells bearing incompatible sec-9 and plp-1 alleles, Allorecognition and cell death are induced, which are dependent upon physical interaction between SEC-9 and PLP-1. The central NBD and patatin-like phospholipase activity of PLP-1 are essential for Allorecognition and cell death, while the TPR domain and the polymorphic SNARE domain of SEC-9 function in conferring allelic specificity. Our data indicate that fungal NLR-like proteins function similar to NLR immune receptors in plants and animals, showing that NLRs are major contributors to innate immunity in plants and animals and for Allorecognition in fungi.

  • identification of Allorecognition loci in neurospora crassa by genomics and evolutionary approaches
    Molecular Biology and Evolution, 2015
    Co-Authors: Jiuhai Zhao, Pierre Gladieux, Elizabeth Hutchison, Joanna Bueche, Charles Hall, Fanny Perraudeau, Louise N Glass


    Understanding the genetic and molecular bases of the ability to distinguish self from nonself (Allorecognition) and mechanisms underlying evolution of Allorecognition systems is an important endeavor for understanding cases where it becomes dysfunctional, such as in autoimmune disorders. In filamentous fungi, Allorecognition can result in vegetative or heterokaryon incompatibility, which is a type of programmed cell death that occurs following fusion of genetically different cells. Allorecognition is genetically controlled by het loci, with coexpression of any combination of incompatible alleles triggering vegetative incompatibility. Herein, we identified, characterized, and inferred the evolutionary history of candidate het loci in the filamentous fungus Neurospora crassa. As characterized het loci encode proteins carrying an HET domain, we annotated HET domain genes in 25 isolates from a natural population along with the N. crassa reference genome using resequencing data. Because Allorecognition systems can be affected by frequency-dependent selection favoring rare alleles (i.e., balancing selection), we mined resequencing data for HET domain loci whose alleles displayed elevated levels of variability, excess of intermediate frequency alleles, and deep gene genealogies. From these analyses, 34 HET domain loci were identified as likely to be under balancing selection. Using transformation, incompatibility assays and genetic analyses, we determined that one of these candidates functioned as a het locus (het-e). The het-e locus has three divergent allelic groups that showed signatures of positive selection, intra- and intergroup recombination, and trans-species polymorphism. Our findings represent a compelling case of balancing selection functioning on multiple alleles across multiple loci potentially involved in Allorecognition.

Gad Shaulsky – 3rd expert on this subject based on the ideXlab platform

  • cellular Allorecognition and its roles in dictyostelium development and social evolution
    The International Journal of Developmental Biology, 2019
    Co-Authors: Peter Kundert, Gad Shaulsky


    The social amoeba Dictyostelium discoideum is a tractable model organism to study cellular Allorecognition, which is the ability of a cell to distinguish itself and its genetically similar relatives from more distantly related organisms. Cellular Allorecognition is ubiquitous across the tree of life and affects many biological processes. Depending on the biological context, these versatile systems operate both within and between individual organisms, and both promote and constrain functional heterogeneity. Some of the most notable Allorecognition systems mediate neural self-avoidance in flies and adaptive immunity in vertebrates. D. discoideum’s Allorecognition system shares several structures and functions with other Allorecognition systems. Structurally, its key regulators reside at a single genomic locus that encodes two highly polymorphic proteins, a transmembrane ligand called TgrC1 and its receptor TgrB1. These proteins exhibit isoform-specific, heterophilic binding across cells. Functionally, this interaction determines the extent to which co-developing D. discoideum strains co-aggregate or segregate during the aggregation phase of multicellular development. The Allorecognition system thus affects both development and social evolution, as available evidence suggests that the threat of developmental cheating represents a primary selective force acting on it. Other significant characteristics that may inform the study of Allorecognition in general include that D. discoideum’s Allorecognition system is a continuous and inclusive trait, it is pleiotropic, and it is temporally regulated.

  • the polymorphic proteins tgrb1 and tgrc1 function as a ligand receptor pair in dictyostelium Allorecognition
    Journal of Cell Science, 2017
    Co-Authors: Shigenori Hirose, Gong Chen, Adam Kuspa, Gad Shaulsky


    Allorecognition is a key factor in Dictyostelium development and sociality. It is mediated by two polymorphic transmembrane proteins, TgrB1 and TgrC1, that contain extracellular immunoglobulin domains. TgrB1 and TgrC1 are necessary and sufficient for Allorecognition and they carry out separate albeit overlapping functions in development, but their mechanism of action is unknown. Here we show that TgrB1 acts as a receptor and TgrC1 as its ligand in cooperative aggregation and differentiation. The proteins bind each other in a sequence-specific manner, TgrB1 exhibits a cell-autonomous function, and TgrC1 acts non-cell-autonomously. The TgrB1 cytoplasmic tail is essential for its function and it becomes phosphorylated upon association with TgrC1. Dominant mutations in TgrB1 activate the receptor function and confer partial ligand independence. These roles in development and sociality suggests that Allorecognition is critical in the integration of individual cells into a coherent organism.

  • altered n glycosylation modulates tgrb1 and tgrc1 mediated development but not Allorecognition in dictyostelium
    Journal of Cell Science, 2015
    Co-Authors: Chenglin Frank Li, Gong Chen, Amanda Nicole Webb, Gad Shaulsky


    ABSTRACT Cell surface adhesion receptors play diverse functions in multicellular development. In Dictyostelium , two immunoglobulin-like adhesion proteins, TgrB1 and TgrC1, are essential components with dual roles in morphogenesis and Allorecognition during development. TgrB1 and TgrC1 form a heterophilic adhesion complex during cell contact and mediate intercellular communication. The underlying signaling pathways, however, have not been characterized. Here, we report on a mutation that suppresses the tgrB–tgrC1 -defective developmental arrest. The mutated gene alg9 encodes a putative mannosyl transferase that participates in N- linked protein glycosylation. We show that alteration in N- linked glycosylation, caused by an alg9 mutation with a plasmid insertion ( alg9 ins ) or tunicamycin treatment, can partially suppress the developmental phenotypes caused by tgrC1 deletion or replacement with an incompatible allele. The alg9 ins mutation also preferentially primed cells toward a stalk-cell fate. Despite its effect on development, we found that altered N- linked glycosylation had no discernable effect on TgrB1-TgrC1-mediated Allorecognition. Our results show that N- linked protein glycosylation can modulate developmental processes without disturbing cell-cell recognition, suggesting that tgrB1 and tgrC1 have distinct effects in the two processes.