Mammalian adenylyl cyclase family members are randomly located on different chromosomes

Molecular cloning studies have elucidated the presence of multiple isoforms of mammalian adenylyl cyclase. So far, six different isoforms (I to VI) have been fully characterized. Comparison of their structural and biochemical characteristics suggests that the mammalian adenylyl cyclase family can be classified into four sub-families: type I, type III, type II/IV, and type V/VI. We have determined the chromosomal localization of these genes. Type I gene was assigned to chromosome 7, type III to chromosome 2, types II and IV to chromosomes 5 and 14, and types V and VI to chromosomes 3 and 12. Our results indicate that the different adenylyl cyclase isoforms, even within the same subfamily, are distributed randomly in the genome, in contrast to the chromosomal organization of other components within the same signaling pathway, such as catecholamine receptors and G proteins.     

The genes for human gastrin and cholecystokinin are located on different chromosomes

Summary The polypeptide hormones gastrin and cholecystokinin are structurally related, having the identical pentapeptide GWMDF located at their C-terminus. The precursors to these two hormones also show amino acid homology, suggesting that they may have a common ancestral origin. Recombinant DNA clones corresponding to gene fragments encoding human gastrin and cholecystokinin were used to determine their respective chromosomal localization by analyzing human-rodent cell lines. We have assigned the cholecystokinin gene to human chromosome 3q12-3pter and the gastrin gene to chromosome 17q.     

The human desmin and vimentin genes are located on different chromosomes

We have used somatic cell hybrids of Chinese hamster X man and mouse X man to localize the genes (des and vim) encoding the intermediate filaments desmin and vimentin in the human genome. Southern blots of DNA prepared from each cell line were screened with hamster cDNA probes specific for des and vim genes, respectively. The single-copy human des gene is located on chromosome 2, and the single-copy human vim gene is assigned to chromosome 10. Partial restriction maps of the two human genomic loci are presented. A possible correlation of the des locus with several reported hereditary myopathies is discussed.     

The gene and the pseudogene for mouse p53 cellular tumor antigen are located on different chromosomes.

The chromosomal assignments of the two genes encoding the murine p53 cellular tumor antigen were determined by using a panel of mouse-Chinese hamster somatic cell hybrid clones and a mouse p53-specific cDNA clone. One gene, probably the functional member of the family, was found to be on chromosome 11. The other gene, which is probably a processed pseudogene, was assigned to chromosome 14. The potential relevance of these findings to documented cases of chromosome 11 trisomy are also discussed.     

CD200 is a ligand for all members of the CD200R family of immunoregulatory molecules

CD200Fc, a chimeric molecule including the extracellular domain of CD200 and a murine IgG2a Fc region, regulates immune responses following engagement of a cell surface receptor, CD200R, expressed on cells of the myeloid and T cell lineage. A recent report focused attention on a family of CD200Rs, but concluded that only one member used CD200 as its ligand. We have also cloned and sequenced a family of CD200Rs, but identify an amino terminus to two of the three isoforms not recognized by previous researchers. We show by FACS, using FITC-labeled CD200Fc, that COS7 cells transfected with all CD200R isoforms bind CD200 as ligand, although the functional consequences of this binding likely differs between the different isoforms. mAbs directed against the CD200 R1/R4 isoforms altered IL-2/IL-4 cytokine production and suppressed CTL responses in a fashion comparable to CD200Fc, with a significantly lesser effect seen following addition of anti-CD200 R2/R3.     

Human thymosin-beta 4/6-26 gene is part of a multigene family composed of seven members located on seven different chromosomes

We have isolated a cDNA encoding the human interferon-inducible gene 6-26, by screening a cDNA library with an oligodeoxynucleotide probe. Its sequence was found to be identical to that of the human thymosin-beta 4 cDNA, which encodes a protein present in most cell types, but whose function is not clear at present. By hybridization of the thymosin-beta 4/6-26 cDNA to the DNA of a panel of human-rodent somatic cell hybrids, we found that at least seven genes homologous to this cDNA are present in the human genome. We localized these genes, some of which might be pseudogenes, to seven distinct chromosomes, namely, chromosomes 1, 2, 4, 9, 11, 20, and X.     

Rodent IgE-binding factor genes are members of an endogenous, retrovirus-like gene family

Synthesis of IgE by B lymphocytes can be regulated by soluble lymphocyte factors which have affinity for the Fc region of IgE (IgE-binding factors). In previous studies, we identified cDNA clones encoding rodent IgE-binding factors by direct expression in transfected mammalian cells. Here we show that IgE-binding factor cDNA clone 8.3 is a member of the endogenous, retrovirus-like intracisternal A-particle gene family of the mouse. This conclusion is supported by blot hybridization, DNA sequence comparisons, heteroduplex analysis, and immunochemical cross-reactivity of the encoded proteins. The results identify a member of this highly reiterated gene family with a role in regulation of the allergic immune response.     

Subfamilies of histone H3 and H4 genes are located on most,possibly all of the chromosomes in maize

Summary It has been previously shown that in the genome of maize the multiple copies of the histone H3 and H4 multigenic families are organized into eight to ten subfamilies each containing a variable number of copies. Each subfamily is characterized by a specific proximal environment and thus can be revealed by blot-hybridization with its specific 5 probe. Restriction fragment length polymorphism (RFLP) combined with monosomic analysis was used to localize several H3 and H4 subfamilies on maize chromosomes. H3 and H4 genes were found to be located on most, possibly all of the chromosomes, revealing a remarkably dispersed organization of these multigenic families.     

The genes coding for the muscle contractile proteins, myosin heavy chain, myosin light chain 2, and skeletal muscle actin are located on three different chromosomes

[This corrects the article on p. 1299 in vol. 1.].     

Lipid transfer protein genes of loblolly pine are members of a complex gene family

A loblolly pine (Pinus taeda L.) cDNA with properties of a nonspecific lipid transfer protein (nsltp) is reported. In contrast to simple family structures reported for a variety of angiosperm nsltp genes, the putative pine nsltp gene is a member of a complex family.     

The human genes for calbindin 27 and 29 kDa proteins are located on chromosomes 8 and 16, respectively

Genomic clones coding for the brain calcium-binding protein, calbindin 29 kDa, were isolated from a human library. A fragment containing exon 2 was used as a probe to investigate the presence of the gene in human x rodent somatic cell hybrids. The gene was unambiguously assigned to chromosome 16. The closely-related calbindin 27 kDa gene was previously assigned to chromosome 8. These two genes, deriving from a common ancestor, thus appear to have been separated during vertebrate evolution.     

The Arabidopsis Athb-8, -9 and genes are members of a small gene family coding for highly related HD-ZIP proteins

We report the isolation and characterization of two Arabidopsis homeobox genes highly related to the Athb-8 gene. The full-length cDNAs encode proteins of 841 and 852 amino acids which we have designated Athb-9 and -14, respectively. Athb-8, -9 and -14 are members of a small family of HD-Zip proteins (HD-ZIP III) characterized by a HD-Zip motif confined to the N-terminus of the polypeptide. The spatial organization of the HD-Zip domain of Athb-8, -9 and -14 is different from that of the Athb-1 (a member of the HD-ZIP I family) and Athb-2 (a member of the HD-ZIP II family) HD-Zip domains. DNA binding analysis performed with random-sequence DNA templates showed that the Athb-9 HD-Zip (HD-Zip-9) domain, but not the Athb-9 HD alone, binds to DNA. The HD-Zip-9 domain recognizes a 11 bp pseudopalindromic sequence (GTAAT(G/C)ATTAC), as determined by selecting high-affinity binding sites from random-sequence DNA. Moreover, gel retardation assays demonstrated that the HD-Zip-9 domain binds to DNA as a dimer. These data support the notion that the HD-ZIP III domain interacts with DNA recognition elements in a fashion similar to the HD-ZIP I and II domains.     

The genes coding for the muscle contractile proteins, myosin heavy chain, myosin light chain 2, and skeletal muscle actin are located on three different mouse chromosomes.

The chromosomal distribution of murine genes expressed during differentiation of skeletal muscle cells was determined by Southern blot analysis of DNA from mouse-Chinese hamster hybrid cell lines containing incomplete subsets of mouse chromosomes. All detectable myosin heavy chain genes are located on chromosome 11. The gene for the myosin light chain 2 is located on chromosome 7. The skeletal muscle alpha-actin gene and several other actin genes, or pseudogenes, are located on chromosome 3. Additional actin DNA sequences are distributed on other mouse chromosomes.     

Six genes of the human connexin gene family coding for gap junctional proteins are assigned to four different human chromosomes

Connexin genes code for proteins that form cell-to-cell channels known as gap junctions. The genes for the known connexins 26, 32, 43, and 46 have been assigned to human chromosomes, 13, X, 6, and 13, respectively, by analysis of a panel of human-mouse somatic cell hybrids using rat cDNA probes. A pseudogene of connexin 43 that lacks an intron of the cx43 gene has been located on human chromosome 5. Furthermore, the genes of the two new connexins 37 and 40 have both been assigned to human chromosome 1. Thus the human chromosomes 1 and 13 each carry at least two different connexin genes. Their exact location on these chromosomes is not yet known. From our results subchromosomal assignments can be deduced for the human cx32 gene to Xq13-p11, the human cx37 gene as well as the human cx40 gene to 1pter-q12, and the human cx43 gene to 6q14-qter. The generation of the connexin multigene family from a hypothetical ancestral connexin gene is discussed.     

Concerted evolution of members of the multisequence family chAB4 located on various nonhomologous chromosomes

During the last years it became obvious that a lot of families of long-range repetitive DNA elements are located within the genomes of mammals. The principles underlying the evolution of such families, therefore, may have a greater impact than anticipated on the evolution of the mammalian genome as a whole. One of these families, called chAB4, is represented with about 50 copies within the human and the chimpanzee genomes and with only a few copies in the genomes of gorilla, orang-utan, and gibbon. Members of chAB4 are located on 10 different human chromosomes. FISH of chAB4-specific probes to chromosome preparations of the great apes showed that chAB4 is located, with only one exception, at orthologous places in the human and the chimpanzee genome. About half the copies in the human genome belong to two species-specific subfamilies that evolved after the divergence of the human and the chimpanzee lineages. The analysis of chAB4-specific PCR-products derived from DNA of rodent/human cell hybrids showed that members of the two human-specific subfamilies can be found on 9 of the 10 chAB4-carrying chromosomes. Taken together, these results demonstrate that the members of DNA sequence families can evolve as a unit despite their location at multiple sites on different chromosomes. The concerted evolution of the family members is a result of frequent exchanges of DNA sequences between copies located on different chromosomes. Interchromosomal exchanges apparently take place without greater alterations in chromosome structure. Received: 20 March 1997 / Accepted: 13 September 1997     

The genes coding for the cardiac muscle actin, the skeletal muscle actin and the cytoplasmic beta-actin are located on three different mouse chromosomes.

The actins are a group of highly conserved proteins encoded by a multigene family. We have previously reported that the skeletal muscle actin gene is located on mouse chromosome 3, together with several other unidentified actin DNA sequences. We show here that the gene coding for the cardiac muscle actin, which is closely related to the skeletal muscle actin (1.1% amino acid replacements), is located on mouse chromosome 17. The gene coding for the cytoplasmic beta-actin is located on mouse chromosome 5. Thus, these three actin genes are located on three different chromosomes.     

Mapping genes located on human chromosomes 2 and 12 to porcine chromosomes 15 and 5

Informative microsatellites associated with two genes on HSA12 (lysozyme, LYZ; tumour necrosis factor receptor, TNFR) and one gene on HSA2 (glutamic acid decarboxylase 1, GAD1) were mapped in the US Meat Animal Research Center (MARC) swine reference population and the physical assignment of a-lactalbumin (LALBA) was determined. A comparative map for HSA2 and HSA12 with SSC15 and SSC5, respectively, was developed by combining the results from this study with published type I loci mapped in both species. One rearrangement between HSA2 and SSC15 was detected while the number of rearrangements between HSA12 and SSC5 were numerous. These results indicated that conservation of synteny does not imply a conservation of gene order and that additional type I markers need to be mapped in the pig to fully understand the chromosomal rearrangements that occurred during the evolution of mammals.     

Isolation, characterization, and mapping of the mouse and human WDR8 genes, members of a novel WD-repeat gene family

The Trp-Asp (WD) motif has been shown to exist in a number of proteins. Genes containing repeats of the WD motif compose a large gene family associated with a variety of cellular functions and can be divided into a number of functional subfamilies. By means of the differential display method using ttw, a mouse model for the early stage of ectopic ossification, we have identified a novel mouse gene, Wdr8 (WD repeat domain 8), which contains two WD repeats, together with its human orthologue. The human and mouse WDR8 genes encode 460 and 462 amino acids, respectively, with 89% identity, and are expressed in almost all tissues, including bone and cartilage, and in bone-forming cells, including osteoblasts and chondrocytes. Wdr8 expression in cartilage was differentially displayed by stimuli for ectopic ossification in ttw and was observed strongly only at a transition period from hypertrophic to mineralizing stages in ATDC5, a chondrogenic cell line that exhibits endochondral ossification, suggesting a potential role for Wdr8 in the process of ossification. The WDR8 protein is highly conserved among a variety of species, but is distinctly different from other WD-repeat proteins, indicating that it represents a novel subfamily of the WD-repeat gene family.