Primitive synteny of vertebrate major histocompatibility complex class I and class II genes

Ohta, Yuko; Okamura, Koji; McKinney, E. Churchill; Bartl, Simona; Hashimoto, Keiichiro; Flajnik, Martin F.

doi:10.1073/pnas.97.9.4712

Cited by 150 publications

(123 citation statements)

References 42 publications

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“…7, which is published as supplemental data on the PNAS web site, www.pnas.org). These data are consistent with previous observations that, in at least some regions of the genome, pufferfish speciation has been accompanied by particularly high rates of chromosomal rearrangements (61)(62)(63)(64). It is possible that genome compression in the pufferfish has been achieved, at least in part, by clustering together genes with shared domains of expression.…”

Section: Expression Of the Pufferfish Scl Gene In Transgenic Zebrafishsupporting

confidence: 81%

Regulation of the stem cell leukemia ( SCL ) gene: A tale of two fishes

Barton

Göttgens

Gering

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The stem cell leukemia (SCL) gene encodes a tissue-specific basic helix-loop-helix (bHLH) protein with a pivotal role in hemopoiesis and vasculogenesis. Several enhancers have been identified within the murine SCL locus that direct reporter gene expression to subdomains of the normal SCL expression pattern, and long-range sequence comparisons of the human and murine SCL loci have identified additional candidate enhancers. To facilitate the characterization of regulatory elements, we have sequenced and analyzed 33 kb of the SCL genomic locus from the pufferfish Fugu rubripes, a species with a highly compact genome. Although the pattern of SCL expression is highly conserved from mammals to teleost fish, the genes flanking pufferfish SCL were unrelated to those known to flank both avian and mammalian SCL genes. These data suggest that SCL regulatory elements are confined to the region between the upstream and downstream flanking genes, a region of 65 kb in human and 8.5 kb in pufferfish. Consistent with this hypothesis, the entire 33-kb pufferfish SCL locus directed appropriate expression to hemopoietic and neural tissue in transgenic zebrafish embryos, as did a 10.4-kb fragment containing the SCL gene and extending to the 5 and 3 flanking genes. These results demonstrate the power of combining the compact genome of the pufferfish with the advantages that zebrafish provide for studies of gene regulation during development. Furthermore, the pufferfish SCL locus provides a powerful tool for the manipulation of hemopoiesis and vasculogenesis in vivo.T he stem cell leukemia (SCL) gene (also known as Tal-1) encodes a basic helix-loop-helix (bHLH) transcription factor that is a critical regulator of both hemopoiesis and vasculogenesis (1). SCL is normally expressed in hemopoietic stem cells, in committed cells of the erythroid, myeloid, and megakaryocytic lineages, in endothelium, and within specific regions of the central nervous system, a pattern of expression that is highly conserved across vertebrate species from mammals to teleost fish (2-6).SCL is essential for the development of all hemopoietic lineages (7,8). A role in early progenitors is also suggested by the observation that expression of anti-sense SCL suppressed the proliferation, cell cycle progression, and self renewal of a multipotent hemopoietic cell line (9). Distinct functions following lineage commitment are implied by the modulation of SCL mRNA and protein levels during erythroid and myeloid differentiation (10-14). Moreover, enforced SCL expression enhanced erythroid differentiation of hemopoietic cell lines (14, 15) and increased erythroid and megakaryocytic differentiation of normal CD34-positive progenitors (16,17).SCL also plays a crucial role in the formation of hemangioblasts, bipotent progenitors of both blood and endothelium. Ectopic expression of SCL mRNA in zebrafish embryos specifies hemangioblast formation from early mesoderm and results in excessive production of blood and endothelial progenitors (3). In keeping with this, SCL can parti...

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Section: Expression Of the Pufferfish Scl Gene In Transgenic Zebrafishsupporting

confidence: 81%

Regulation of the stem cell leukemia ( SCL ) gene: A tale of two fishes

Barton

Göttgens

Gering

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…Genomic library was made from nurse shark "yellow" in LambdaFix II (Stratagene, La Jolla, CA). Low-stringency hybridization conditions were 30% formamide washing to 2Â SSC/0.1% SDS at 55 C and high-stringency hybridization conditions were 50% formamide washing to 0.2Â SSC/0.1% SDS at 65 C. PCR was used to label all probes as previously described [41] and free nucleotides were removed with Quick-Spin Sephadex G-50 columns (Roche, Basel, Switzerland). Probes routinely labeled to 3Â10 7 cpm.…”

Section: Methodsmentioning

confidence: 99%

Four primordial immunoglobulin light chain isotypes, including λ and κ, identified in the most primitive living jawed vertebrates

Criscitiello

Flajnik

2007

Eur J Immunol

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The discovery of a fourth immunoglobulin (Ig) light (L) chain isotype in sharks has revealed the origins and natural history of all vertebrate L chains. Phylogenetic comparisons have established orthology between this new shark L chain and the unique Xenopus L chain isotype r. More importantly, inclusion of this new L chain family in phylogenetic analyses showed that all vertebrate L chains can be categorized into four ancestral clans originating prior to the emergence of cartilaginous fish: one restricted to elasmobranchs (r-cart/type I), one found in all cold-blooded vertebrates (r/teleost type 2/elasmobranch type IV), one in all groups except bony fish (k/elasmobranch type II), and one in all groups except birds (j/elasmobranch type III/teleost type 1 and 3). All four of these primordial L chain isotypes (r, r-cart, k and j) have maintained separate V region identities since their emergence at least 450 million years ago, suggestive of an ancient physiological distinction of the L chains. We suggest that, based upon unique, discrete sizes of complementarity determining regions 1 and 2 and other features of the V region sequences, the different L chain isotypes arose to provide different functional conformations in the Ig binding site when they pair with heavy chains.

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“…While class I proteins are expressed on all nucleated cell surfaces, class II proteins are expressed only on B lymphocytes, macrophages, and other antigen-presenting cells of the immune system. In mammals, and in many other vertebrates, the two classes are linked in a single gene complex (Kulski et al 2002;Ohta et al 2000). In humans, this complex is found on chromosome 6.…”

Section: Introductionmentioning

confidence: 99%

Diversifying and Purifying Selection in the Peptide Binding Region of DRB in Mammals

Furlong

Yang

2008

J Mol Evol

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The class II genes of the major histocompatibility complex encode proteins which play a crucial role in antigen presentation. They are among the most polymorphic proteins known, and this polymorphism is thought to be the result of natural selection. To understand the selective pressure acting on the protein and to examine possible differences in the evolutionary dynamics among species, we apply maximum likelihood models of codon substitution to analyze the DRB genes of six mammalian species: human, chimpanzee, macaque, tamarin, dog, and cow. The models account for variable selective pressures across codons in the gene and have the power to detect amino acid residues under either positive or negative selection. Our analysis detected positive selection in the DRB genes in each of the six mammals examined. Comparison with structural data reveals that almost all amino acid residues inferred to be under positive selection in humans are in the peptide binding region (PBR) and are in contact with the antigen side chains, although residues outside of but close to the PBR are also detected. Strong purifying selection is also detected in the PBR, at sites which contact the antigen and at sites which may be involved in dimerization or T cell binding. The analysis demonstrates the utility of the random-sites analysis even when structural information is available. The different mammalian species are found to share many positively or negatively selected sites, suggesting that their functional roles have remained very similar in the different species, despite the different habitats and pathogens of the species.

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Primitive synteny of vertebrate major histocompatibility complex class I and class II genes

Cited by 150 publications

References 42 publications

Regulation of the stem cell leukemia ( SCL ) gene: A tale of two fishes

Regulation of the stem cell leukemia ( SCL ) gene: A tale of two fishes

Four primordial immunoglobulin light chain isotypes, including λ and κ, identified in the most primitive living jawed vertebrates

Diversifying and Purifying Selection in the Peptide Binding Region of DRB in Mammals

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