Duplicated zinc finger protein genes on the proximal short arm of the human X chromosome: isolation, characterization and X-inactivation studies.

Two highly similar zinc finger genes, ZXDA (Zinc finger, X-linked, Duplicated) and ZXDB, have been isolated and characterized. Both map to the proximal short arm region of the human X chromosome, near locus DXS422 in Xp11.21. Both genes are expressed in several human tissues, revealing a approximately 6.5 kb mRNA by Northern blot hybridization, and both are subject to X-inactivation. A comparison of 1.2 kb of cDNA sequence from a single exon in the open reading frames of the two genes reveals 98.7% identity in nucleotide sequence. The predicted proteins include at least ten tandem C2-H2 zinc finger motifs. When cDNA probes from different parts of the genes are hybridized to a blot of different animal DNAs, two bands are seen in all placental mammals, suggesting that the duplication predates the radiation of placental mammals and is highly conserved. Furthermore, under conditions of lowered stringency, additional bands are seen in several species, suggesting that the two genes reported here may be members of a larger zinc finger gene family.

Pericentromeric structure of human X "isochromosomes": evidence for molecular heterogeneity.

Three different long-arm X isochromosomes and an isodicentric X chromosome were examined by in situ hybridization with X-chromosome-specific alpha-satellite probes and by quantitation of Southern blots hybridized with proximal short-arm probes. Each chromosome had a unique pericentromeric structure. The isodicentric X chromosome was clearly dicentric, showing two distinct alpha-satellite hybridization signals and duplication of short-arm material. Two isochromosomes showed a larger than normal, bifid alpha-satellite signal and also had duplications of different extents of short-arm material. The third X isochromosome could not be distinguished from a classical long-arm isochromosome; it did not have a short-arm duplication and it had a single alpha-satellite signal. These data indicate that rearrangements responsible for X isochromosome formation can occur at numerous locations in the pericentromeric region and that some X isochromosomes may involve duplications of substantial portions of the short arm.

Segregation ratios within Segregation Distorter lines of Drosophila melanogaster conform to a beta-binomial distribution.

Segregation Distorter (SD) chromosomes are preferentially recovered from SD/SD+ males due to the dysfunction of sperm bearing the SD+ chromosome. The proportion of offspring bearing the SD chromosome is given the symbol k. The nature of the frequency distribution of k was examined by comparing observed k distributions produced by six different SD chromosomes, each with a different mean, with k distributions predicted by two different statistical models. The first model was one where the k of all males with a given SD chromosome were considered to be equal prior to the determination of those gametes which produce viable zygotes. In this model the only source of variation of k would be binomial sampling. The results rigorously demonstrated for the first time that the observed k distributions did not fit the prediction that the only source of variation was binomial sampling. The next model tested was that the prior distribution of segregation ratios conformed to a beta distribution, such that the distribution of k would be a beta-binomial distribution. The predicted distributions of this model did not differ significantly from the observed distributions of k in five of the six cases examined. The sixth case probably failed to fit a beta-binomial distribution due to a major segregating modifier. The demonstration that the prior distribution of segregation ratios of SD lines can generally be approximated with a beta distribution is crucial for the biometrical analysis of segregation distortion.

Linkage and segregation distortion in Drosophila melanogaster.

Segregation distortion is caused by a group of genetic elements in and near the centric heterochromatin of chromosome 2 of Drosophila melanogaster. These elements promote their preferential recovery in heterozygous males by rendering sperm bearing the homologous chromosome dysfunctional. Previous work has shown that numerous Y-autosome translocations are associated with the suppression of the segregation distorter phenotype. The present study examined the effects of translocations between the major autosomes upon the expression of segregation distortion. Autosomal translocations involving either the segregation distorter chromosome or its sensitive homologue had no significant effect upon the expression of segregation distortion. These results argue that linkage arrangement per se may not have a major effect on segregation distortion. The suppression of SD by specific Y-autosomal translocations may be due to the disruption of elements on the Y chromosome that are important for the expression of SD.

Further observations on the nature of radiation-induced chromosomal interchanges recovered from Drosophila sperm.

The induction and analysis of numerous translocations (identified genetically and characterized cytologically) between chromosomes 2 and 3 of Drosophila melanogaster have allowed us to reexamine three issues concerning the nature of radiation-induced interchanges in spermatozoa. First, our results support the idea that, relative to their mitotic metaphase length, all major chromosomal regions are similar in their breakability, whether euchromatic (proximal or distal) or heterochromatic. Second, analysis of all our reciprocal exchanges between the two chromosomes shows a statistically significant dependence of the position of the chromosome 2 breakpoint on that of the chromosome 3 breakpoint. Thirdly, our combined cytological and genetic approach strengthens the results of previous analyses, which suggested a strong tendency for chromosomal interchanges to be of the reciprocal type in multiple-break rearrangements. This indicates that if radiation induces chromosome breaks, then the resulting broken ends tend to rejoin in pairs rather than independently.

Further Characterization of Genetic Elements Associated with the Segregation Distorter Phenomenon in DROSOPHILA MELANOGASTER.

Segregation Distorter, SD, associated with the second chromosome of Drosophila melanogaster, is known to cause sperm bearing the non-SD homologue to dysfunction in heterozygous males. In earlier studies, using different, independently derived, SD chromosomes, three major loci were identified as contributing to the distortion of segregation ratios in males. In this study the genetic components of the SD-5 chromosome have been the subjects of further investigation, and our findings offer the following information. Crossover analysis confirms the mapping of the Sd locus to a position distal to but closely linked with the genetic marker pr. Spontaneous and radiation-induced recombinational analyses and deficiency studies provide firm support to the notion that the Rsp (Responder) locus lies within the proximal heterochromatin of chromosome 2, between the genetic markers lt and rl and most likely in the heterochromatin of the right arm. The major focus of this study, however, has been on providing a better definition of the genetic properties of the Enhancer of SD [E(SD)]. Our findings place this locus within the region of the two most proximal essential genes in the heterochromatin of the left arm of chromosome 2. Moreover, our analysis reveals a probable association of the E(SD) locus with a meiotic drive independent of that caused by Sd.

Chromosome replacement in mixed populations of compound-2L; free-2R and standard strains of Drosophila melanogaster : An example of unstable genetic isolation.

Crosses between compound-2L; free-2R (free-arm) and standard strains of Drosophila melanogaster produce two classes of inviable aneuploid hybrids in equal proportions: monosomic 2L and trisomic 2L. The lethal period for monosomics occurs during embryogenesis while the trisomics survive to late pupae. Since the hybrids are inviable, standard and free-arm strains within a mixed population remain genetically isolated. Genetic isolation in the absence of mating isolation offers an extreme example of unstable equilibrium. Relative fitness data indicate that an unstable equilibrium will be established between free-arm and standard strains at a ratio of 2.5∶1. Indeed, in three cage experiments established at initial ratios of 3∶1, free arms to standards, laboratory (Oregon R) or native (Okanagan S) standard strains were completely replaced in approximately 100 days by free-arm lines derived either from laboratory or from native genetic background. In contrast, one cage established at an initial ratio of 4∶1 failed to show replacement and for 92 days remained at approximately the initial ratio. Subsequent genetic analysis of flies removed from this cage identified the presence of an anomalous strain through which genetic information was transferred reciprocally between the free-arm and standard lines. The second chromosomes carried by this strain consisted of a free-2R and a standard second on the right arm of which was attached a duplication for all of 2L. While the origin of the 2L·2R+2L chromosome was uncertain, genetic and cytological examinations revealed that it represented the reciprocal crossover product expected from an exchange that generated a F(2R). Additional crosses disclosed that the transmission frequency of the asymmetrical pair of second chromosomes, as well as their right-arm crossover products, was disproportionately in favor of the short arm. Since unequal transmission was invariably greater from female parents, this phenomenon was viewed as further evidence in support of the drag hypothesis.