Dosage compensation in Drosophila occurs by a twofold increase in transcription per copy of X-linked genes in males (XY) compared with females (XX). msl-1 is one of four genes that are essential for dosage compensation in males, and Msl-1 protein is associated specifically with the male X chromosome. To explore the basis for the sex specificity of dosage compensation, Msl-1 expression was examined in males, females, and dosage compensation mutants. Msl-1 protein levels are negatively regulated by Sxl in females, resulting in male-specific expression of Msl-1. In addition, msl-2 is required for translation and/or stability of Msl-1 in males. Furthermore, the wild-type pattern of Msl-1 localization to the X chromosome is dependent on mle and msl-3 function, although a subset of sites are stained with Msl-1 antibodies in these mutants. Collectively, these data provide the first evidence for an order of msl gene function and suggest that male-specific expression of Msl-1 plays a key role in the sex specificity of dosage compensation (Palmer, 1994).
A total of 7,416 ethyl methanesulfonate (EMS)-treated second chromosomes and 6,212 EMS-treated third chromosomes were screened for sex-specific lethals. Four new recessive male-specific lethal mutations were recovered. When in homozygous condition, each of these mutations kills males during the late larval or early pupal stages, but has no detectable effect in females. One mutant, mlets, is a temperature sensitive allele of maleless, mle, while the other three mutants identify two new loci: male-specific lethal-1 (msl-1) (two alleles) at map position 2-53.3 and male-specific lethal-2 (msl-2) at 2-9.0. The male-specific lethality associated with these mutants is not related to the sex per se of the mutant flies, since sex-transforming genes fail to interact with these mutations. Moreover, the presence or absence of a Y chromosome in males or females has no influence on the male-specific lethal action of these mutations. Finally, no single region of the X chromosome, when present as a duplication, is sufficient to rescue males from the lethal effects of msl-1 or msl-2. These results suggest that the number of complete X chromosomes determines whether a fly homozygous for a male-specific lethal mutation lives or dies (Belote, 1980).
Bacteria that selectively kill males ('male-killers') were first characterized more than 50 years ago in Drosophila and have proved to be common in insects. However, the mechanism by which sex specificity of virulence is achieved has remained unknown. This study tested the ability of Spiroplasma poulsonii to kill Drosophila melanogaster males carrying mutations in genes that encode the dosage compensation complex. The bacterium failed to kill males lacking any of the five protein components of the complex (Veneti, 2005).
Certain isofemale lines of Drosophila only give rise to daughters following the death of male embryos. Male death is due to the presence of intracellular bacteria that pass from a female to her progeny and that selectively kill males during embryogenesis. These male-killing bacteria are found in a wide range of other insect species, and many different bacteria have evolved male-killing phenotypes. In some host species, male-killers drive the host population sex ratio to levels as high as 100 females per male and alter the pattern of mate competition. However, the underlying processes that produce male-limited mortality are unclear. This study examined the interaction between the male-killing bacterium Spiroplasma poulsonii and the sex determination pathway of D. melanogaster (Veneti, 2005).
The primary signal of sex in Drosophila is the X-to-autosome ratio. This signal is permanently established in expression of Sex-lethal (Sxl) in females and its absence in males. This, in turn, effects three processes: germline sexual identity, somatic sexual differentiation, and dosage compensation, the process by which the gene expression titer on the X chromosome is equalized between two sexes despite their difference in X chromosome number. Mutations in the gene tra that convert XX individuals to male somatic sex do not induce female death. These observations indicate germline formation and migration happen correctly in male embryos and that dying male embryos do not express Sxl. Therefore, the requirement of the Spiroplasma for genes within the system of dosage compensation was examined (Veneti, 2005).
In Drosophila, the single X of males is hypertranscribed. This process of hypertranscription requires the formation of the dosage compensation complex (DCC) and its binding to (and modification of) the X chromosome. SXL in female Drosophila inhibits the production of MSL-2 protein, which is thus only present in male Drosophila. MSL-2 forms a complex with four other proteins, MSL-1, MSL-3, MLE, and MOF, which collectively form the DCC. MSL-1, MSL-3, MLE, and MOF are constitutively present in both males and females and are also supplied maternally. The complete DCC binds, with JIL-1, to the male X chromosome at various entry points, and, with the products of two noncoding RNAs, RoX1 and RoX2, it affects the modification of the single X chromosome and its hypertranscription (Veneti, 2005).
The effect was examined of mutations within the host DCC on the ability of the male-killer to function. The survival of male progeny beyond embryogenesis to L2/L3 (and in one case adult) was scored in the presence of different loss-of-function mutations within the dosage compensation system (normal male-killing occurs during embryogenesis), in the presence and absence of infection. Because many genes within this group additionally show strong maternal effects, the effect of mutations was in each case tested by using both mothers that were heterozygous for the loss-of-function mutation and mothers homozygous for it (Veneti, 2005).
Uninfected males homozygous for loss-of-function mutations within the dosage compensation system generally survive to the third larval instar. Survival to the third larval instar was studied for loss-of-function alleles of msl-1 (alleles msl-11 and msl-1b), msl-2 (msl-2g227 and msl-2g134), msl-3 (msl-3132), mle (mle9, mle1), and mof (mof1), and survival to adult for mle1/mle6 transheterozygotes. In the case of all alleles of msl-1, msl-3, mle, and mof, a similar pattern is observed: Males homozygous or hemizygous for the loss-of-function mutation have appreciable survival in the presence of infection when their mother is also homozygous for the loss-of-function mutation. In contrast, heterozygous male embryos that were siblings of the above (that will have a wild-type DCC) were always killed, as were all male embryos in the case where the mother was heterozygous (where maternal supply of these proteins enables dosage compensation to be initiated, although not maintained). In the case of mle1/mle6 transheterozygotes, male survival to adult was observed. For the case of mof, male-killing was restored to full efficiency when 18H1, a transgenic copy of mof, was added to the mof1 loss-of-function background. Within the above crosses, three observations make sure the observation that Spiroplasma was fully operational. First, crosses involving heterozygous mothers, where male-killing was complete, were conducted concurrently with those using homozygous mothers, and the females in these crosses were siblings from the same vials. Second, in each cross and vial where homozygous males survived, heterozygous males (with wild-type function) still died. Finally, F1 females derived from these crosses, when mated to wild-type males, produced a full, female-biased sex ratio (Veneti, 2005).
In the case of msl-2, where there is no maternal supply of MSL-2, survival of homozygous sons was observed for both homozygous and heterozygous mothers for the case of the mutation msl-2g134. For the case of msl-2 g227, no male progeny were observed from infected females (table S5). This mutation does not rescue males in the assay, probably because the two mutations have different effects on msl-2 expression. The msl-2g134 allele prevents formation of MSL-2 protein, whereas msl-2 g227 potentially encodes the RING-finger element of a truncated MSL-2 protein (Veneti, 2005).
Thus, absence or reduced function of any of the proteins of the DCC can reduce the efficiency of male killing, and a functional DCC is required for male killing by S. poulsonii. The fact that the genes mediating this process in Drosophila have been well studied can be exploited to yield further insights into the mechanism of male killing (Veneti, 2005).
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date revised: 10 August 2012
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