Chemokines are small, inducible, structurally related proteins that guide cells expressing the right chemokine receptors to sites of immune response. They have been identified and studied extensively ...in mammals, but little is known about their presence in other vertebrate groups. Here we describe seven new chemokines in bony fish and one in a cartilaginous fish, as well as one chemokine receptor in a jawless vertebrate. All eight chemokines belong to the SCYA (CC) subfamily characterized by four conserved cysteine residues of which the first two are adjacent. The chemokine receptor is of the CXCR4 type. Phylogenetic analysis does not reveal any clear evidence of orthology of fish and human chemokines. Although the divergence of the subfamilies began before the fish-tetrapod split, much of the divergence within the subfamilies took place separately in the two vertebrate groups. The existence of a chemokine receptor in the lamprey indicates that chemokines are apparently also present in the Agnatha.
An expressed sequence tag obtained from a sea lamprey ( Petromyzon marinus) cDNA library was used to obtain a full-length coding sequence showing significant similarity to ABCB transporter proteins. ...The sequence is closely related to the mammalian ABCB9 protein and the TAP1 and TAP2 proteins that transport peptides for loading onto nascent Mhc class I molecules. The Pema-ABCB9 gene has an exon-intron organization similar to that of the mammalian TAP genes, with the exception of exon 2, which in the lamprey is split into two by a 949-bp long intron. The gene probably occurs in a single copy in the haploid lamprey genome. The ABCB9 genes appear to be evolving four-to-ten times slower than the TAP1 and TAP2 genes. Six putative transmembrane helices and the nucleotide-binding domain of the lamprey ABCB9 protein show high sequence similarity with the TAP1 and TAP2 molecules. The lamprey protein also contains sequence stretches that resemble the putative peptide interacting parts of the TAP1 and TAP2 molecules, but are peppered with ABCB9-specific residues.
The macrophage migration inhibitory factor (MIF) is a cytokine produced by T lymphocytes and macrophages in response to inflammatory stimuli. We sequenced MIF cDNA clones of two jawless fishes, the ...sea lamprey (
Petromyzon marinus) and the North Atlantic hagfish (
Myxine glutinosa), as well as of the jawed (cichlid) fish
Paralabidochromis chilotes. The fish MIF-encoding genes have the same exon–intron organization as the mammalian MIF genes and are present in one copy per haploid genome. Secondary and tertiary structure predictions suggest that the fish MIF proteins have a topology characteristic of the entire MIF-family of proteins. Phylogenetic analysis separates the known nematode members of the family into two groups, one having a sister group relationship with the mammalian
d-dopachrome tautomerase (DDT) proteins and the other being related to vertebrate MIFs. It also reveals a high degree of convergent evolution among the members of the family. Finally, it suggests that the divergence of MIF and DDT occurred before the emergence of nematodes in metazoan evolution.
Gene frequencies of eight Siberian populations (Mansi, Tuva, Todja, Tofalar, Buryat, Okhotsk Evenki, Ulchi, and Negidal) were determined for the three most polymorphic HLA class II loci ( DRB1, DQA1, ...and DQB1) by a combination of single-stranded conformational polymorphism typing and DNA sequencing. The number of alleles per population ranged from 16 to 25, from seven to eight, and from nine to 14 for the DRB1, DQA1, and DQB1 loci, respectively. The alleles at the three loci occurred in 66 different combinations (haplotypes), most of which appeared to be of ancient origin, but some may have arisen within the Siberian populations. Phylogenetic analysis of the frequency data suggests that the HLA genes of Asian and indigenous American populations stem from a single pool distinct from the gene pools of European and African populations. The Asian populations separate into two clusters, one of which encompasses nearly all the Siberian populations and all the indigenous American populations tested, while the other consists of Central, Eastern, and Southeastern Asian populations. The position of the Tuva people appears to be near the node from which the two clusters diverge. The divergence time of the two clusters is estimated to be 21,000-24,000 years BP. Three different branches of the native Siberian peoples seem to have contributed founders for the indigenous American ethnic groups.
To shed light on the origin of adaptive immunity, a cDNA library was prepared from purified lymphocyte-like cells of a jawless vertebrate, the sea lamprey (Petromyzon marinus). Randomly selected cDNA ...clones were sequenced, and their homologies to proteins in the databases were determined. Of the sequences homologous to proteins involved in immune responses, five were selected for further characterization. Their encoding genes corresponded to loci that in jawed vertebrates are essential for activities of lymphocytes. These activities include regulation of T and B cell stimulation and proliferation (CD45); stabilization of molecular complexes involved in lymphocyte activation, adhesion, migration, and differentiation (CD9/CD81); adaptor functions in signaling leading to the activation of B lymphocytes (BCAP) and T lymphocytes (CAST); and amino acid transport associated with cell activation (CD98). The presence of these genes in the lamprey genome and their expression in lymphocyte-like cells support the notion that these cells perform many of the functions of gnathostome lymphocytes. It reopens the question of the stage jawless fishes reached in the evolution of their immune system.
Lymphocyte-like cells in the intestine of the sea lamprey, Petromyzon marinus, were isolated by flow cytometry under light-scatter conditions used for the purification of mouse intestinal ...lymphocytes. The purified lamprey cells were morphologically indistinguishable from mammalian lymphocytes. A cDNA library was prepared from the lamprey lymphocyte-like cells, and more than 8,000 randomly selected clones were sequenced. Homology searches comparing these ESTs with sequences deposited in the databases led to the identification of numerous genes homologous to those predominantly or characteristically expressed in mammalian lymphocytes, which included genes controlling lymphopoiesis, intracellular signaling, proliferation, migration, and involvement of lymphocytes in innate immune responses. Genes closely related to those that in gnathostomes control antigen processing and transport of antigenic peptides could be ascertained, although no sequences with significant similarity to MHC, T cell receptor, or Ig genes were found. The data suggest that the evolution of lymphocytes in the lamprey has reached a stage poised for the emergence of adaptive immunity.
CD45 of jawed vertebrates is a receptor-type protein tyrosine phosphatase regulating lymphocyte development and activation. To shed light on the evolution of the CD45 gene, the organization of its ...orthologue in the lamprey, a jawless vertebrate, was determined. Compared to its mammalian and fugu counterparts, the lamprey gene was found to be lacking several exons in the segment encoding the extracellular part of the protein. In consequence, this part contains only one instead of the two or three fibronectin type III domains typical of the mammalian molecules. The lamprey transcripts of the CD45 gene occur in several variants originating by alternative splicing, including some not observed previously in other vertebrates. Most remarkable of these are splice variants generated by the use of intra-exonic splicing signals and thus lacking one half, one third, or two thirds of an exon and yet apparently translated in the correct reading frame. The lamprey gene contains polymorphic sites not only in the segment encoding the extracellular portion but also in the segment specifying the cytoplasmic part of the molecule. Polymorphism is generated by both mutations and recombination. Some of the alleles may have persisted long enough to represent transspecies polymorphism presumably maintained by positive selection. Phylogenetic analysis suggests that ancestors of the CD45 gene may have existed before the divergence of coelomate from pseudocoelomate metazoans.
Allelic frequencies at the three most polymorphic loci of the HLA class II region (DRB1, DQA1, and DQB1) were determined in 24 Nganasans and 17 Kets, the remnants of the two most ancient groups of ...the Lower Yenisey River/Taimyr Peninsula region in northern Siberia. By single-stranded conformational polymorphism typing, verified by sequencing the corresponding segments of genomic DNA, 19 HLA-DRB1-DQA1-DQB1 haplotypes and 15 HLA-DRB1, 7 DQA1, and 11 DQB1 alleles were found. The most frequent alleles were DRB1*1301(23.5%), DQA1*0103 (29.4%), *0501/03/05 (29.4%), and DQB1*0301/0309 (32.4%) in the Kets, and DRB1*0901 (25%), DQA1*0301 (39.6%), and DQB1 *0301/0309 (37.5%) in the Nganasans. The distribution patterns and comprehensive phylogenic analysis based on the haplotype frequencies of 17 Siberian populations suggest that the founders of both Kets and Nganasans came from Paleolithic populations in the Altai-Sayan Upland. The high frequency of the DRB1*0901 allele in the Uralic-speaking Nganasans may be the result of a relatively recent gene flow from the northwardly-expanding Tungus-speaking Evenki who originated in the Baikal area.
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