Interchromosomal Interactions Research Articles

Interchromosomal repeat array interactions between chromosomes 4 and 10: a model for subtelomeric plasticity.

Chromosomal rearrangements occur more frequently in subtelomeric domains than in other regions of the genome and are often associated with human pathology. To further elucidate the plasticity of subtelomeric domains, we examined the 3.3 kb D4Z4 repeat array on chromosome 4 and its homologue on chromosome 10 in 208 Dutch blood donors by pulsed field gel electrophoresis. These subtelomeric repeats are known to rearrange and partial deletions of this polymorphic array on chromosome 4 are associated with facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant myopathy. Our results show that mitotic rearrangements occur frequently as 3% of individuals display somatic mosaicism for a repeat expansion or contraction explaining the high variability of subtelomeric repeat array sizes. Translocated 4-type repeat arrays on chromosome 10 and the reverse configuration of 10-type repeat arrays on chromosome 4 are observed in 21% of individuals. The translocated repeat arrays on chromosome 4 tend to be more heterogeneous than 4-type repeats on chromosome 10. The repeat length on chromosome 4 is on average larger than on chromosome 10. But on both chromosomes we observe a multi-modal repeat length distribution with equidistant peaks at intervals of 65 kb, possibly reflecting a higher-order chromatin structure. Interestingly, in as many as six random blood donors (3%) we identified FSHD-sized 4-type repeat arrays. Assuming that these individuals are clinically unaffected, these results imply an incomplete penetrance in the upper range of FSHD alleles. Overall, the observed dynamic characteristics of these homologous domains may serve as a model for subtelomeric plasticity.

Synergistic Gene Interactions Control the Induction of the Mitochondrial Uncoupling Protein (Ucp1) Gene in White Fat Tissue

Among a selected group of mouse strains susceptible to dietary obesity, those with an enhanced capacity for Ucp1 and brown adipocyte induction in white fat preferentially lost body weight following adrenergic stimulation. Based on the generality of this mechanism for reducing obesity, a genetic analysis was initiated to identify genes that control brown adipocyte induction in white fat depots in mice. Quantitative trait locus (QTL) analysis was performed using the variations of retroperitoneal fat Ucp1 mRNA expression in progeny of genetic crosses between the A/J and C57BL/6J parental strains and selected AXB recombinant inbred strains. Three A/J-derived loci on chromosomes 2, 3, and 8 and one C57BL/6J locus on chromosome 19 were linked to Ucp1 induction in retroperitoneal fat. Although A/J-derived alleles seemed to contribute to elevated Ucp1 expression, the C57BL/6J allele on chromosome 19 increased Ucp1 mRNA to levels higher than parental values. Thus, novel patterns of C57BL/6J and A/J recombinant genotypes among the four mapped loci resulted in a transgressive variation of Ucp1 phenotypes. Although the extent of the interchromosomal interactions have not been fully explored, strong synergistic interactions occur between a C57BL/6J allele on chromosome 19 and an A/J allele on chromosome 8. In addition to selective synergistic interactions between loci, variations in recessive and dominant effects also contribute to the final levels of Ucp1 expression.

Functional dissection of in vivo interchromosome association in Saccharomyces cerevisiae.

Homologue pairing mediates both recombination and segregation of chromosomes at meiosis I. The recognition of nucleic-acid-sequence homology within the somatic nucleus has an impact on DNA repair and epigenetic control of gene expression. Here we investigate interchromosomal interactions using a non-invasive technique that allows tagging and visualization of DNA sequences in vegetative and meiotic live yeast cells. In non-meiotic cells, chromosomes are ordered in the nucleus, but preferential pairing between homologues is not observed. Association of tagged chromosomal domains occurs irrespective of their genomic location, with some preference for similar chromosomal positions. Here we describe a new phenomenon that promotes associations between sequence-identical ectopic tags with a tandem-repeat structure. These associations, termed interchromosome trans-associations, may underlie epigenetic phenomena.

Progression of meiotic DNA replication is modulated by interchromosomal interaction proteins, negatively by Spo11p and positively by Rec8p

Spo11p is a key mediator of interhomolog interactions during meiosis. Deletion of the SPO11 gene decreases the length of S phase by approximately 25%. Rec8p is a key coordinator of meiotic interhomolog and intersister interactions. Deletion of the REC8 gene increases S-phase length, by approximately 10% in wild-type and approximately 30% in a spo11Delta background. Thus, the progression of DNA replication is modulated by interchromosomal interaction proteins. The spo11-Y135F DSB (double strand break) catalysis-defective mutant is normal for S-phase modulation and DSB-independent homolog pairing but is defective for later events, formation of DSBs, and synaptonemal complexes. Thus, earlier and later functions of Spo11 are defined. We propose that meiotic S-phase progression is linked directly to development of specific chromosomal features required for meiotic interhomolog interactions and that this feedback process is built upon a more fundamental mechanism, common to all cell types, by which S-phase progression is coupled to development of nascent intersister connections and/or related aspects of chromosome morphogenesis. Roles for Rec8 and/or Spo11 in progression through other stages of meiosis are also revealed.

Spatial differences in patterns of modification: selection on hairy in Drosophila melanogaster wings.

Artificial selection was carried out for over 45 generations to enhance and suppress expression of the mutation hairy on the Drosophila melanogaster wing. Whole chromosome mapping of X-linked and autosomal modifiers of sense organ number displayed regional differences in magnitude and direction of their effects. Regional specificity of modifier effects was also seen in some interchromosomal interactions. Scanning electron microscopy allowed precise measurement of sense organ size and position along the L3 longitudinal wing vein. Sense organ size varied in a predictable fashion along the proximal-distal axis, and the dorsal pattern differed from the ventral pattern. The high and low selection lines differed most in the proximal portion of the L3 vein. Extra sense organs in the High line were often associated with vein fragments at locations predicted from ancestral vein patterns. Thus, regional specificity of polygenic or quantitative trait locus modifier effects was identified in several different parts of the wing.

A proline-rich region in the Zeste protein essential for transvection and white repression by Zeste.

The DNA-binding protein encoded by the zeste gene of Drosophila activates transcription and mediates interchromosomal interactions such as transvection. The mutant protein encoded by the zeste1 (z1) allele retains the ability to support transvection, but represses white. Similar to transvection, repression requires Zeste-Zeste protein interactions and a second copy of white, either on the homologous chromosome or adjacent on the same chromosome. We characterized two pseudorevertants of z1 (z1-35 and z1-42) and another zeste mutation (z78c) that represses white. The z1 lesion alters a lysine residue located between the N-terminal DNA-binding domain and the C-terminal hydrophobic repeats involved in Zeste self-interactions. The z78c mutation alters a histidine near the site of the z1 lesion. Both z1 pseudorevertants retain the z1 lesion and alter different prolines in a proline-rich region located between the z1 lesion and the self-interaction domain. The pseudorevertants retain the ability to self-interact, but fail to repress white or support transvection at Ultrabithorax. To account for these observations and evidence indicating that Zeste affects gene expression through Polycomb group (Pc-G) protein complexes that epigenetically maintain chromatin states, we suggest that the regions affected by the z1, z78c, and pseudorevertant lesions mediate interactions between Zeste and the maintenance complexes.

Population and behaviour genetics of Drosophila ananassae

Drosophila ananassae is a cosmopolitan and domestic species. It occupies a unique status among the Drosophila species due to certain peculiarities in its genetic behaviour. The most unusual feature of this species is spontaneous male recombination in appreciable frequency. The present review summarizes the work done on population and behaviour genetics of D. ananassae from India. Population dynamics of three cosmopolitan inversions has been studied in Indian populations of D. ananassae and it is evident from the results that there is a considerable degree of genetic divergence at the level of inversion polymorphism. In general, the populations from south India show more differentiation than those from the north. These three cosmopolitan inversions, which are coextensive with the species, exhibit heterosis. Interracial hybridization does not lead to breakdown of heterosis, which suggests that evidence for coadaptation is lacking in geographic populations of D. ananassae. Heterosis appears to be simple luxuriance rather than populational heterosis (coadaptation). Unlinked inversions occur in random associations, indicating no interchromosomal interactions. However, two inversions of the third chromosome often show strong linkage disequilibrium in laboratory populations, which is due to epistatic gene interaction and suppression of crossing-over. Genetic variations for certain allozyme polymorphism and sternopleural bristle phenotypes in Indian populations of D. ananassae have also been observed. A number of investigations have also been carried out on certain aspects of behaviour genetics of Indian D. ananassae. There is evidence for sexual isolation within D. ananassae. Significant variations in mating propensity of several isofemale strains, inversion karyotypes, the diminishing effects of certain mutations on sexual activity of males and positive response to selection for high and low mating propensity provide evidence for genetic control of sexual behaviour in D. ananassae. Males contribute more to variation and thus are more subject to intra-sexual selection than females. Evidence for rare male mating advantage has also been presented. Geographic strains of D. ananassae show variation with respect to oviposition site preference. The results of studies on pupation site preference, which is an important component of larval behaviour, suggest that larval pupation behaviour in D. ananassae is under polygenic control with a substantial amount of additive genetic variation.

Parental origin of the X chromosome in a patient with a Robertsonian translocation and Turner's syndrome.

We report on a proband with both a Robertsonian translocation and Turner's syndrome. Study of the parental origin of the X chromosome performed by microsatellite analysis indicates paternal origin of the X chromosome (Xpat). The occurrence of chromosome aberrations as a consequence of interchromosomal interactions is discussed.

The role of recombination and RAD52 in mutation of chromosomal DNA transformed into yeast.

While transformation is a prominent tool for genetic analysis and genome manipulation in many organisms, transforming DNA has often been found to be unstable relative to established molecules. We determined the potential for transformation-associated mutations in a 360 kb yeast chromosome III composed primarily of unique DNA. Wild-type and rad52 Saccharomyces cerevisiae strains were transformed with either a homologous chromosome III or a diverged chromosome III from S. carlsbergensis. The host strain chromosome III had a conditional centromere allowing it to be lost on galactose medium so that recessive mutations in the transformed chromosome could be identified. Following transformation of a RAD+ strain with the homologous chromosome, there were frequent changes in the incoming chromosome, including large deletions and mutations that do not lead to detectable changes in chromosome size. Based on results with the diverged chromosome, interchromosomal recombinational interactions were the source of many of the changes. Even though rad52 exhibits elevated mitotic mutation rates, the percentage of transformed diverged chromosomes incapable of substituting for the resident chromosome was not increased in rad52 compared to the wild-type strain, indicating that the mutator phenotype does not extend to transforming chromosomal DNA. Based on these results and our previous observation that the incidence of large mutations is reduced during the cloning of mammalian DNA into a rad52 as compared to a RAD+ strain, a rad52 host is well-suited for cloning DNA segments in which gene function must be maintained.

A further study of interchromosomal epistatic interaction in male mating activity of Drosophila melanogaster.

The interchromosomal epistatic interaction between second and third chromosomes was investigated for male mating activity of Drosophila melanogaster. The observed mating activity of double chromosome homozygotes is 0.526 +/- 0.044, whereas the expected one under the multiplicative model is calculated to be 0.511 +/- 0.038. These two male mating activities are in excellent agreement, indicating no interchromosomal epistasis. The coefficient of interaction, i, is quantified as -0.174 +/- 0.168. The magnitude of the k statistic, another index of epistasis, is 0.0001 +/- 0.0267. Neither index of epistasis differs statistically from zero. The result also shows that there is little or no epistatic interaction between two major chromosomes. However, one interchromosomal synthetic sterility was found in 26 chromosome lines. These results are combined with those of Kosuda (1985) and the generality of epistatic interaction is discussed.

Axial shortening during pachynema unrelated to nonhomologous synapsis

The pachytene behavior of chromosomes participating in quadrivalent formation in male mice heterozygous for T(X;4)7Rl or T(X;4)8Rl was analyzed in electron micrographs of microspread spermatocytes. In each population of nuclei from the translocation heterozygotes, the longest 4X axes were approximately the proportional length expected from the respective contributions of the 4 and the X estimated from breakpoint positions in mitotic chromosomes. However, the 4X axis of these translocation quadrivalents undergoes extensive shortening. In both R7 and R8 the shortest 4X axis observed in the population of nuclei was approximately the length of the normal 4 axis. This equalization of axial lengths suggests that there may be an interchromosomal interaction between synapsed chromosomes. In R8, axial shortening of the 4X occurs as pachynema progresses. In both translocations, shortening is accompanied by twisting of the 4X around the 4. Both axial shortening and twists are characteristics exhibited by chromosomal axes of unequal length as part of the meiotic phenomenon described as "synaptic adjustment" (Moses, 1977). Synaptic adjustment involves, in addition, nonhomologous synapsis, which is delayed until the latter part of pachynema. However, axial shortening in R7 and R8 is not accompanied by nonhomologous synapsis. In R7, nonhomologous synapsis does not occur; in R8, it is confined to quadrivalents in which the 4X axis is near its maximum length (i.e., early). This behavior suggests that axial shortening and nonhomologous synapsis during the progression of pachynema (previously considered collectively under the term "synaptic adjustment") are not necessarily coupled events.

A homologous subfamily of satellite III DNA on human chromosomes 14 and 22

We describe a new subfamily of human satellite III DNA that is represented on two different acrocentric chromosomes. This DNA is composed of a tandemly repeated array of diverged 5-base-pair monomer units of the sequence GGAAT or GGAGT. These monomers are organised into a 1.37-kilobase higher-order structure that is itself tandemly reiterated. Using a panel of somatic cell hybrids containing specific human chromosomes, this higher-order structure is demonstrated on chromosomes 14 and 22, but not on the remaining acrocentric chromosomes. In situ hybridisation studies have localised the sequence to the proximal p-arm region of these chromosomes. Analysis by pulsed-field gel electrophoresis (PFGE) reveals that 70-110 copies of the higher-order structure are tandemly organised on a chromosome into a major domain which appears to be flanked on both sides by non-tandemly repeated genomic DNA. In addition, some of the satellite III sequences are interspersed over a number of other PFGE fragments. This study provides fundamental knowledge on the structure and evolution of the acrocentric chromosomes, and should extend our understanding of the complex process of interchromosomal interaction which may be responsible for Robertsonian translocation and meiotic nondisjunction involving these chromosomes.

Analysis of dominance for competitive ability in Drosophila melanogaster

In these experiments the genetic basis of larval competition in Drosophila melanogaster was investigated. Competitive ability was defined by a series of regression coefficients relating larval performance to their mono- and duo-culture densities. Sixteen inter-related F1 hybrids were individually compared with their parents, revealing the presence of large amounts of dominance and heterosis for the various competitive parameters, all directed towards improved competitive ability. Analysis of the F1 hybrids amongst themselves revealed that most of the heterosis was due to either interchromosomal interaction, or the complementing action of haploid autosomes and relatively little was due to any specific interaction between the homologues. The relevance of these results to the current understanding of heterosis is discussed.

Genetic analysis of larval competition in Drosophila melanogaster.

A chromosome assay was employed to determine the genetic basis of the competitive ability of the larvae of Drosophila melanogaster when competing for a controlled amount of food. The effects of increasing stress due to intra- and inter-genotypic competition were analysed using a yield-density regression analysis producing estimates of the absolute performance at a standard reference density (e-values), the magnitude of intra-genotypic competition and the inter-genotypic competitive effect of one genotype on another. A distinction was made between the Sensitivity and the Pressure components of inter-genotypic competition. The probability of survival and mean adult weight were used as measures of competitive success. The genetic analysis revealed high levels of heterosis for the e-values and inter-genotypic pressure, with correspondingly high inter-chromosomal interactions. Inter-genotypic sensitivity was less consistently heterotic and less epistatic. All dominance was directed towards a competitively superior genotype and both major autosomes were involved in the determination of competitive ability with the greater effect residing on the third chromosome. There was evidence of early non-competitive larval mortality in one of the two sets of substitution lines investigated and the effect of this on the estimation of the genetic parameters is discussed.

Chromosomal effects in egg laying of Drosophila melanogaster under different conditions

Differences in the genetic determination of egg laying under three different conditions (in a suitable medium, in a non-suitable one and egg laying by virgin females) were studied through chromosome assay in two pairs of inbred lines. Egg laying of inseminated females on the suitable medium showed directional dominance and interchromosomal interactions, as expected for a trait related to fitness. Egg laying on the suitable and the non-suitable media are related, as suggested by the correspondence of some genetical effects. The difference between the egg laying in the two situations, which could be seen as a measure of retention, was affected by additive and heterotic effects. A chromosome mediating higher egg output than its holologue on the suitable medium can mediate a lower egg output on the non-suitable one. This shows that genotype x environment interaction cannot be due only to proportionate effects of all the relevant genes, but that different genes are acting in the two situations. The genetical effects on egg laying of virgin females were very different of those in the other two situations. This is an essentially additive trait, which suggests that it is not related to fitness.

Effects of chromosomal interaction on male mating activity in Drosophila melanogaster.

The epistatic interaction between the second and third chromosomes of D. melanogaster was quantified in male mating activity under no competition among males. The mean mating activity of the two-chromosome homozygote was 0.517±0.064. The expected value under a multiplicative model was 0.509±0.054. Coefficient of interaction, I, was calculated to be 0.008±0.129. k statistic, a new measure of epistasis devised by Seager and Ayala (1982), was 0.029±0.027, which is not significantly different from zero. It is concluded that there is no interchromosomal interaction between two major autosomes in male mating activity.

Investigation of interchromosomal interactions among three major chromosomes of Drosophila melanogaster in response to environments and the relationship between multi-line and two-line analyses: Re-examination of caligari and mather data

Multi-factor interations in Caligari and Mather's (1975) ANOVA for eight substitution lines of Drosophila melanogaster in nine invironments were examined by cluster analysis. The results indicate a concise explanation of both types of interchromosomal interactions—that which determines the average effect of genotype and that which determines the ordinary genotype-environment (GE) interaction—as follows. For chaeta number, when only one of the three major chromosomes (X, II, and III) of W-stock is substituted by S-stock, the phenotypic values do not change. However, if more than one chromosome is substituted, they change and differ among themselves. The same pattern holds for yield of offspring with respect to S-stock. The data were also investigated by a two-line analysis using an extension of Mather and Caligari's (1976) approach. The statistics for testing the hypothesis of no dependency of GE interaction between a pair of contrasting chromosome ( i. e., g values) against the background chromosome, which the pair has in common, are closely related to a component of ANOVA in the eight-line analysis. For those data the g values are shown not to be independent of the background chromosomes. An implication of these analyses is that genes which control average effect and those which control sensitivity to environmental change can be conditionally dependent on other genes of the same type within a chromosome.

On intra- and interchromosomal associations in Drosophila ananassae

In Drosophila ananassae, three cosmopolitan inversions are very common in natural populations. Chromosomal polymorphism due to these inversions often persists when strains are maintained in the laboratory. A chromosomal analysis of a number of strains was made. Data on the frequencies of different gene sequences will be described separately. During the present investigation the same data have been analyzed in order to test the intra- and interchromosomal interactions in D. ananassae. The results reveal that interchromosomal interactions do not occur with respect to viability as unlinked inversions are associated randomly. However, the linked inversions of the third chromosome show non-random associations maintained by epistatic gene interaction and suppression of crossing over.

Polygenic analysis of pattern formation: Interdependence among veins in the same compartment of the Drosophila wing

Polygenic modifiers of the L4 and L5 wing veins in Drosophila simulans were used to study the degree of genetic independence of veins within the same developmental compartment. The L4 and L5 were selected for opposite changes in length. Whole-chromosome assays of heterozygous effects showed that the L4 and L5 polygenic modifiers were associated with differences both in chromosomes and in interchromosomal interactions. A comparison of selection responses confirmed that, though some modifiers had strictly vein-specific action, others acted either upon all veins within the posterior compartment or upon all veins in the wing. The results support the idea that some genes control pattern formation in the wing as a whole, others regulate structures within a single compartment, and still others are limited to a single element within a compartment.

A chromosome substitution analysis of geotactic maze behavior inDrosophila melanogaster

Positive and negative geotactic maze behaviors were selected in strains of Drosophila melanogaster, for over 40 generations on 15-unit classification mazes. A chromosome substition analysis of these behaviors was undertaken to determine which of the three major chromosomes is most important in causing the differences in geotactic maze behavior between the divergent strains. By following the appropriate mating scheme, every possible homozygous chromosomal combination of the X, II, and III chromosomes from the geopositive and geonegative strain was produced. Heterozygous combinations were also produced to test for dominance and interchromosomal interactions. The results indicate that all three chromosomes are involved in geotactic behavior. The order of importance was II greater than III greater than X. Dominance effects were found in females of the X chromosome from the geopositive strain and for the III chromosome from the geonegative strain. No evidence for interchromosomal interactions was uncovered.