Xdh, xanthine dehydrogenase, XOR, Xanthine DH
Gene model reviewed during 5.47
Low-frequency RNA-Seq exon junction(s) not annotated.
There is only one protein coding transcript and one polypeptide associated with this gene
1335 (aa); 146.9 (kD predicted)
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\ry using the Feature Mapper tool.
GBrowse - Visual display of RNA-Seq signalsView Dmel\ry in GBrowse 2
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
ry alleles have been detected by several criteria, including electrophoretic mobility of XDH, purine sensitivity and rosy eye color, either in the absence or presence of allopurinol. Chovnick and his colleagues (Chovnick, Gelbart, and McCarron, 1980) identify at least seven different electromorphs in laboratory stocks; using a highly discriminating series of gel conditions, Buchanan and Johnson (1983) identified, among 62 wild-type chromosomes isolated from nature, fourteen electromorphs, two of which corresponded to those contained among the earlier seven. Both induced mutations and natural variable sites are designated by the number of the + progenitor followed by specific derivative numbers, e.g. ry102 is the second mutant derivative of ry+1d. Not all mutants with allelic designations with values less than 100 are known to be derivatives of ry+0; however, those numbered from 3a to 54 (excepting 17, 20 and 21) are known to be so derived. However, those mutations discovered by Girton, Green, Daniels, Lewis, Spradling and Rubin do not use this system of nomenclature. Finally, Chovnick's laboratory maintains several hundred mutants not reported here, including a group generated on a ry+11 background. ry+ allele designation refers to the entire rosy DNA sequence. Electrophoretic markers and control variants characteristic of a given allele represent only a few of the bp polymorphisms distinguishing one ry+ allele from another. ry+ alleles originated as iso-3 stocks from wild populations, with the exception of those marked (derivative) which are conversions to wild type of an unique rosy mutant allele. These may carry bp polymorphisms within the conversion segment not common to the original rosy mutant. 'tentative constitution': Polymorphic sites segregating in wild type alleles; the digits to the left of the slash bar represent the phenotype with respect to the 5' cis-acting control elements, 1005 and 409, with '0' indicating the CRM levels of ry+0, '+' representing higher CRM, and '-' indicating lower CRM. The remaining digits designate the electrophoretic charge relative to that of XDH produced by ry+0 attributable to the amino-acid residues inferred to correspond to the three sites inferred from mapping and sequencing results; the sites are indicated in order and are located at +736, +1551 and +3557 in the gene sequence (Curtis, unpublished): '0' indicates the relative charge at the three sites of ry+0; '-' indicates a more negative charge, i.e. less anodically migrating; and '+' a more positive charge. Nucleotide positions are defined with respect to +1 of the nucleotide sequence defined as the second base pair in an EcoRI site in the second exon; transcription from left to right. The molecular biology was referenced from one or more of the following: Curtis and Bender (unpublished results); Curtis, Clark, Chovnick and Bender, 1989; Gray and Bender (unpublished results); Lee, Curtis, McCarron, Love, Gray, Bender, and Chovnick, 1987.
In a sample of 79 genes with multiple introns, 33 showed significant heterogeneity in G+C content among introns of the same gene and significant positive correspondence between the intron and the third codon position G+C content within genes. These results are consistent with selection adding against preferred codons at the start of genes.
Phylogenetic distribution of introns in the gene coding for ry in 37 species, including 31 dipterans, is analysed. Three narrowly distributed novel introns are identified across the species. The phylogenetic distribution of these introns favours the 'introns-late' theory of the origin of genes. Analysis of the nucleotide sequences indicates that all three introns have arisen by duplication of a preexisting intron, which is pervasive in Drosophila and other dipterans.
The effects on the properties of the enzyme of specific mutations in different regions of the ry protein sequence are studied.
Chromosome homologies of Muller's element D (J chromosome in the Paleartic species and XR chromosome arm in Nearctic species) and of element E (O chromosome in the Paleartic species and 2 chromosome in Nearctic species) have been confirmed by single copy probes in the species of the obscura group and in D.melanogaster.
mRNA levels increase at adult day 5 in strain showing extended longevity phenotype (ELP).
The parameters of meiotic gene conversion tract length distribution have been determined using extensive co-conversion data for selected and unselected sites of known molecular location in the ry locus. The mean conversion tract length of 352 base pairs indicates that gene conversion tract lengths are sufficiently small to allow for extensive shuffling of DNA sequence polymorphisms within a gene. For selected site conversions there is a bias towards recovery of longer tracts, the mean conversion tract length being 706 base pairs. Meiotic gene conversion and P element induced gap repair are distinct processes defined by different parameters and, possibly, mechanisms.
DNA elements 5' to the coding region that are important in proper regulation of expression have little evolutionary conservation in the vicinity of gene homologs.
ry mutants have been characterised from amino acid sequence comparisons and from enzyme activity measurements.
No difference in allele fixed in lines selected over 700 generations for high (negative) and low (positive) geotaxis.
The distribution of ry protein in the tissues of the adult fly is altered in mutants of a number of genes, including bw, ltd, st, w, mal and ca. ry protein is absent from the eye in these mutants, but is present at normal levels in the fat body surrounding the eye as well as in other tissues where it is synthesised. The distribution of ry protein in the tissues of the adult fly is also altered in v and cn mutants; ry protein is absent from the eye in these mutants, but is present at normal levels in the fat body surrounding the eye. The localisation of ry protein within the eye is abnormal in cho and pn mutants.
P element mediated transformation of the ry::Cvic\Xdh chimeric ry gene demonstrates it to be physiologically active. Activity levels are lower than wild type suggesting that the Cvic\Xdh sequences are inefficient for mRNA production or the mRNA is unstable.
ry protein is not synthesised in the eye, but is transported and sequestered there.
The locus has been extensively mapped by reciprocal recombination and conversion studies (see appended maps). Seven different classes of complementing or partially complementing alleles described; complementation map circular (Gelbart et al., 1976). ry+ commonly used as a marker in P-element transformation experiments (Spradling and Rubin, 1982; Rubin and Spradling, 1982).
The structural gene for xanthine dehydrogenase (XDH); it is a homodimer with subunit molecular weight estimated from its DNA sequence as 146,898 daltons (Keith, Riley, Kreitman, Lewontin, Curtis and Chambers, 1987). Enzyme level responds to dose of ry+ alleles (Grell, 1962). XDH is a molybdenum hydroxylase and requires the activity of cin+, lxd+, mal+ for normal activity, though not for normal levels of CRM (Glassman, Shinoda, Duke and Collins, 1968). CRM (cross-reacting material) contains bound molybdenum in the presence of mal; however, enzyme activity inhibited (Andres, 1976). Homozygotes for null alleles lack XDH activity (Forrest, Glassman and Mitchell, 1956; Glassman and Mitchell, 1959; Hubby and Forrest, 1960) and have reddish brown eyes; accumulate enzyme's substrates, xanthine and 2-amino-4-hydroxypteridine as larvae plus hypoxanthine in the adult; precursors collect as solid granules in Malpighian tubules (Bonse, 1967); lack enzyme products uric acid and isoxanthopterin (Mitchell, Glassman and Hadorn, 1959). Mutant homozygotes are also sensitive to administration of purine to the medium (Glassman, 1965); survival on purine supplemented medium can be used to select for rare ry+ recombinants (Chovnick, Ballantyne, Baillie and Holm, 1970) and unequal crossovers producing tandem duplications (Gelbart and Chovnick, 1979). Hypomorphic alleles that have normal eye color are also sensitive to appropriate levels of purine supplementation; furthermore, both wild types and hypomorphs can be made to display mutant eye color by administration of appropriate levels of the XDH inhibitor, HPP (allopurinol) <up>4-hydroxypyrazolo-(3,4-d) pyrimidine</up> (Glassman, 1965; Boni, DeLerma and Parisi, 1967; McCarron and Chovnick, 1981); in vitro and in vivo complementation between mal and ry products was demonstrated by Glassman (1952) (Glassman and McLean, 1962). Pigmentation is nonautonomous in ry eye discs trans- planted into wild-type hosts (Hadorn and Schwink, 1956). Enzyme levels climb from low levels in the zygote to a peak at puparium formation; the level then falls but increases again to a maximum a few days after eclosion (Chovnick, McCarron, Hilliker, O'Donnell, Gelbart and Clark, 1978). Enzyme derived from the paternal genome appears during gastrulation; activity at time zero is low in ry+ zygotes produced by ry/+ females but undetectable in those produced by ry females (Sayles, Browder and Williamson, 1973). Enzyme activity present in larval and adult fat bodies, larval and adult Malpighian tubules, and, in smaller amounts, in various regions of the larval and adult gut (Ursprung and Hadorn, 1961; Munz, 1964; Reaume, Clark, and Chovnick, 1989; Reaume (unpublished observations)</up>. XDH is not synthesized in the adult eye, but is transported there (Reaume, Clark and Chovnick, 1989).