Drosophila dosage compensation

Dosage compensation of X-linked genes is a phenomenon of concerted, chromosome-wide regulation of gene expression underpinned by sustained and tightly regulated histone modifications and chromatin remodeling, coupled with constrains of nuclear architecture. This elaborate process allows the accomplishment of regulated expression of genes on the single male X chromosome to levels comparable to those expressed from the two X chromosomes in females. The ribonucleoprotein Male Specific Lethal (MSL) complex is enriched on the male X chromosome and is intricately involved in this process in Drosophila melanogaster. In this review we discuss the recent advances that highlight the complexity lying behind regulation of gene expression by just two-fold.     

X chromosome sites autonomously recruit the dosage compensation complex in Drosophila males

It has been proposed that dosage compensation in Drosophila males occurs by binding of two core proteins, MSL-1 and MSL-2, to a set of 35–40 X chromosome “entry sites” that serve to nucleate mature complexes, termed compensasomes, which then spread to neighboring sequences to double expression of most X-linked genes. Here we show that any piece of the X chromosome with which compensasomes are associated in wild-type displays a normal pattern of compensasome binding when inserted into an autosome, independently of the presence of an entry site. Furthermore, in chromosomal rearrangements in which a piece of X chromosome is inserted into an autosome, or a piece of autosome is translocated to the X chromosome, we do not observe spreading of compensasomes to regions of autosomes that have been juxtaposed to X chromosomal material. Taken together these results suggest that spreading is not involved in dosage compensation and that nothing distinguishes an entry site from the other X chromosome sites occupied by compensasomes beyond their relative affinities for compensasomes. We propose a new model in which the distribution of compensasomes along the X chromosome is achieved according to the hierarchical affinities of individual binding sites.     

Evolution: good males are bad females

Manipulation of Drosophila melanogaster genomes allows large numbers of genes to be transmitted solely through males, thereby allowing selection to optimize flies for male function alone. It seems biasing phenotypes toward the male optima has serious fitness costs for females.     

Old Iron, Young Copper: from Mars to Venus

Iron and copper are metals which play an important role in the living world. From a brief consideration of their chemistry and biochemistry we conclude that the early chemistry of life used water soluble ferrous iron while copper was in the water-insoluble Cu(I) state as highly insoluble sulphides. The advent of oxygen was a catastrophic event for most living organisms, and can be considered to be the first general irreversible pollution of the earth. In contrast to the oxidation of iron and its loss of bioavailability as insoluble Fe(III), the oxidation of insoluble Cu(I) led to soluble Cu(II). A new iron biochemistry became possible after the advent of oxygen, with the development of chelators of Fe(III), which rendered iron once again accessible, and with the control of the potential toxicity of iron by its storage in a water soluble, non-toxic, bio-available storage protein (ferritin). Biology also discovered that whereas enzymes involved in anaerobic metabolism were designed to operate in the lower portion of the redox spectrum, the arrival of dioxygen created the need for a new redox active metal which could attain higher redox potentials. Copper, now bioavailable, was ideally suited to exploit the oxidizing power of dioxygen. The arrival of copper also coincided with the development of multicellular organisms which had extracellular cross-linked matrices capable of resisting attack by oxygen free radicals. After the initial `iron age' subsequent evolution moved, not towards a `copper age', but rather to an `iron-copper' age. In the second part of the review, this symbiosis of iron and copper is examined in yeast. We then briefly consider iron and copper metabolism in mammals, before looking at iron-copper interactions in mammals, particularly man, and conclude with the reflection that, as in Greek and Roman mythology, a better understanding of the potentially positive interactions between Mars (iron) and Venus (copper) can only be to the advantage of our species.     

Study of dosage compensation in Drosophila

Using a sensitive RT-QPCR assay, we analyzed the regulatory effects of sex and different dosage compensation mutations in Drosophila. To validate the assay, we showed that regulation for several genes indeed varied with the number of functional copies of that gene. We then confirmed that dosage compensation occurred for most genes we examined in male and female flies. Finally, we examined the effects on regulation of several genes in the MSL pathway, presumed to be involved in sex-dependent determination of regulation. Rather than seeing global alterations of either X chromosomal or autosomal genes, regulation of genes on either the X chromosome or the autosomes could be elevated, depressed, or unaltered between sexes in unpredictable ways for the various MSL mutations. Relative dosage for a given gene between the sexes could vary at different developmental times. Autosomal genes often showed deranged regulatory levels, indicating they were in pathways perturbed by X chromosomal changes. As exemplified by the BR-C locus and its dependent Sgs genes, multiple genes in a given pathway could exhibit coordinate regulatory modulation. The variegated pattern shown for expression of both X chromosomal and autosomal loci underscores the complexity of gene expression so that the phenotype of MSL mutations does not reflect only simple perturbations of genes on the X chromosome.     

Fitness effects of female mate choice: preferred males are detrimental for Drosophila melanogaster females

The evolution of female mate choice, broadly defined to include any female behaviour or morphology which biases matings towards certain male phenotypes, is traditionally thought to result from direct or indirect benefits which females acquire when mating with preferred males. In contrast, new models have shown that female mate choice can be generated by sexual conflict, where preferred males may cause a fitness depression in females. Several studies have shown that female Drosophila melanogaster bias matings towards large males. Here, we use male size as a proxy for male attractiveness and test how female fitness is affected by reproducing with large or small males, under two different male densities. Females housed with large males had reduced lifespan and aged at an accelerated rate compared with females housed with small males, and increased male density depressed female fitness further. These fitness differences were due to effects on several different fitness components. Female fitness covaried negatively with male courtship rate, which suggests a cost of courtship. Mating rate increased with male size, whereas female fitness peaked at an intermediate mating rate. Our results suggest that female mate choice in D. melanogaster is, at least in part, a by-product of sexual conflict over the mating rate.     

Chromosomal basis of dosage compensation in Drosophila

3H-thymidine and 3H-uridine labeling patterns of the X-chromosome arms of Drosophila pseudoobscura have been examined autoradiographically. Results show that in all phases of replication, namely, initial, middle and terminal, both arms of the X-chromosome in the male are advanced by one or two steps of 3H-thymidine labeling in comparison with the autosomes, and both arms in the female show more or less similar labeling profile as the autosomes. Both the arms in the male show pale stainability and enlarged width ratio, as reported in other species. The 3H-uridine labeling patterns also reveal that both arms in the male incorporate twice as much precursor as the individual X in the female. Results, therefore, suggest that both arms of the X in D. pseudoobscura are faster replicating and hyperactive in the male, although it is considered that XL is homologous to the X and XR to part of the third chromosome of D. melanogaster.     

Chromosomal basis of dosage compensation in Drosophila

A critical analysis of the puffing activity and transcribing activity patterns of different sites of the X-chromosome of the male and female larval salivary glands of Drosophila hydei has been presented. The results show that within the limitations of the resolving power of the technique and variability inherent in the general chromosomal conditions the puffing activities of the different sites of the X-chromosome are very much alike in the two sexes. Of the 15 puffing sites in the X-chromosome, most of the sites either show good concordance in the two sexes or resemble in their highest class value. Only 4 sites (4CD, 8A, 16C and 20B) show considerable discordance in the activity pattern between male and female. Incorporation of ³H-uridine in the X-chromosome also reveals that there is indeed a reasonable degree of superimposition of the number of silver grains in the X-chromosomal puffs of the two sexes. Whatever disparity that exists between the grain numbers in the two sexes can be explained on the basis of sister-class compensation. These results have been interpreted as evidence in support of the piece-meal mechanism of dosage compensation in Drosophila, operating through hyperactivation in the male.This work has been supported by a grant (No. 10/14/66 G) from the Atomic Energy Establishment, Govt. of India to A.S.M. and a Senior Research Fellowship from the Bhabha Atomic Research Centre, Govt. of India to S.N.C.     

Evolution: when females are brighter than males.

Females are usually considered to be more choosy than males when seeking a mating partner, resulting in the evolution of attractive males. When males are the limiting resource for receptive females, however, the females may become brightly coloured.     

The two-dimensional restriction analysis of Drosophila DNAs: males and females

Two-dimensional restriction analysis has been applied to terminally labeled restriction segments from adult male and female flies that were the progeny of ten successive single-pair, brother-sister matings. Many of the 2500-4000 different bands that can be seen on autoradiographs are of widely different density, a fact that suggests the superposition of multiple restriction segments of similar sequence. The number of bands observed is significantly fewer than expected. Nearly all of the bands seen in male-DNA displays appear equivalent to those seen in female-DNA displays, but a few sex differences (male-dense and female-dense bands) can be identified--much fewer than expected. When the HpaII-MspI test was applied to fractionated BamHI fragments, between 900 and 1800 discrete C-C-G-G sites were found to be cleaved in a completely equivalent fashion by each isoschizomer.