RNA synthesis in Drosophila melanogaster polytene chromosomes indications of simultaneous dosage compensation and dosage effect in X chromosomes

It is shown that the apparent incompleteness of dosage compensation when RNA synthesis is measured autoradiographically is not due to the existence of contiguous dosage compensated and non-dosage compensated genes. Rather this seems to be the result of peculiarities in the coordination of RNA synthesis between the X chromosomes and autosomes. The slope of the line defined by \([\bar X]_i \) and \([\overline {2R} ]_i \) (number of grains over the X and autosomal segments averaged over the different nuclei assayed in each gland) is indistinguishable in males and females (apparent complete dosage compensation). An average of the slopes obtained for different individual glands (from [X] and [2R], the grain counts over each nucleus belonging to a particular gland), on the other hand, has a value in males which is approximately half of the value attained by females (a value of one half, in males, indicates dosage effect since males have one X and females have two).     

How do heterogametic females survive without gene dosage compensation?

When the male is the heterogametic sex (XX♀-XY♂ or XX♀-XO♂), as inDrosophila, orthopteran insects, mammals andCaenorhabditis elegans, X-linked genes are subject to dosage compensation: the single X in the male is functionally equivalent to the two Xs in the female. However, when the female is heterogametic (ZZ♂-ZW♀), as in birds, butterflies and moths, Z-linked genes are apparently not dosage-compensated. This difference between X-linked and Z-linked genes raises fundamental questions about the role of dosage compensation. It is argued that (i) genes which require dosage compensation are primarily those that control morphogenesis and the prospective body plan; (ii) the products of these genes are required in disomic doses especially during oogenesis and early embryonic development; (iii) heterogametic females synthesize and store during oogenesis itself morphogenetically essential gene products - including those encoded by Z-linked genes — in large quantities; (iv) the abundance of these gene products in the egg and their persistence relatively late into embryogenesis enables heterogametic females to overcome the monosomic state of the Z chromosome in ZW embryos. Female heterogamety is predominant in birds, reptiles and amphibians, all of which have megalecithal eggs containing several thousand times more maternal RNA and other maternal messages than eggs of mammals,Caenorhabditis elegans, orDrosophila. This increase in egg size, yolk content and, concomitantly, the size of the maternal legacy to the embryo, may have facilitated female heterogamety and the absence of dosage compensation.     

Gene modulation in Drosophila: Dosage compensation of Pgd + and Zw + genes

The sex-linked Pgd ⁺ and Zw ⁺ genes of Drosophila melanogaster and their associated enzyme activities 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase were employed in an analysis of the relationship between dosage compensation and the location of genes in the genome. In the genotypes examined, the enzyme activity specified by each copy of the gene is twice in males what it is in females. This is true of normal, structurally rearranged, and duplication genotypes. Dosage compensation, therefore, is a regulatory function associated with single structural genes or small chromosomal segments and does not depend on the gene's physical location on the X chromosome.This research was supported by NIH Grant No. 5-R01-HD04859.     

Genetic analysis of the larval secretion gene Sgs-4 and its regulatory chromosome sites in Drosophila melanogaster

Larval salivary gland secretion from seven wild-type stocks of Drosophila melanogaster was electrophoretically analyzed. Considerable variability occurs in the X-chromosomally coded secretion protein 4, both qualitatively, as expressed by differences in electrophoretic mobilities, and quantitatively as seen by its relative amount in the secretion. Drosophila stocks with normal amounts of protein 4 show approximately 80–90% dosage compensation in the males, whereas in two stocks with lower amounts of protein 4 there is no indication of dosage compensation. — Genetic analysis showed that the properties of secretion protein 4 and the level of expression of the Sgs-4 gene are controlled by the X-chromosome. Recombination experiments indicate that the stock-specific characteristics of protein 4 are properties of the structural gene Sgs-4 itself or of a chromosome region immediately adjacent to Sgs-4. One recombinant (R + 79), manifesting an intermediate level of dosage compensation, indicates that a chromosome segment closely distal to Sg-4 is responsible for the regulation of the gene and for dosage compensation in particular. Accordingly, Sgs-4 must be transcribed from distal to proximal. Its position on the genetic map is 3.6. Two stocks, Hikone-R and Kochi-R, which were originally described as 0-mutants produce very low amounts of a specific secretion protein, 4 h, as revealed by a transvection effect and also by fluorography of overloaded gels.Dedicated to Professor W. Beermann on the occasion of his 60th birthday