The relationship between gene dosage, gene expression, and sex in Drosophila

Abstract

In Drosophila, the ratio of the number of X chromosomes to sets of other chromosomes initiates a series of events which result in sexual differentiation. In addition, this ratio establishes dosage compensation, a mechanism which equalizes the products of X-linked genes in males and females. The present review discusses possible genetic entities responsible for the interpretation of chromosomal sex and subsequent sex-mediated regulation during development.Key words: Drosophila, sex chromosomes, gene dosage, gene expression INTRODUCTIONIn Drosophila melanogaster, females have two X chromosomes; males have a single X and a Y. The genetic information contained by the Y chromosome i s not involved in the determination of sex. It is mostly concerned with spermatogenesis and is, therefore, necessary for male fertility. In this particular species of fruit flies, the Y chromosome also bears a cluster of ribosomal RNA cistrons. Sex is determined by the balance of X chromosomes and autosomes in the genome [ 13, and it is generally assumed that there are X-linked female-determining elements whose products are additive [2,3]. In an XX embryo, these products reach the threshold necessary to initiate sexual differentiation along a female mode. When a single X chromosome is present, the threshold is not reached and differentiation proceeds along the male mode It has long been known that, in addition to these purported sex determining genes, the X chromosome contains genes coding for basic metabolic steps or for morphological or physiological products of equal importance to males and females. With few exceptions,* the levels of these gene products are equivalent in the two sexes, leading to the notion that a mechanism exists for the compensation of gene dosage differences that normally occur between males and females.The seminal observation was reported by H.J. Muller at the Sixth International Congress of Genetics [6]. He had noted that the hypomorphic eye color mutant allele white-apricot (Mp) 276Lucchesi deficiency encompassing the gene and bearing, therefore, a single Wa allele had less pigment than homozygous females; males with an extra does of Wa had substantially darker eyes than hemizygous males. The equalization of gene products between chromosomally normal males and females led Muller to postulate the existence of a mechanism of dosage compensation for X-lined genes. He further stated that, although uncovered and more readily studied with mutants, the mechanism must operate on wild-type alleles. Validation of this point came much later with the quantitation of the activity of X-linked enzymes [7].There have been four major landmarks in the study of dosage compensation in Drosophila. The first was the evidence gathered by Mukherjee and Beerman [8] that chromosomal RNA synthesis along the single polytenic X chromosome of male larval salivary glands and the paired X chromosomes of females are equivalent, suggesting that dosage compensation is a transcriptional phenomenon. Another landmark was the demonstration that ge...

Gene dosage compensation in trisomies of Drosophila melanogaster

“…(trisomic 2R) (6) Dose dependent 3.77 Compensated 2.51 *Activity expressed as in Table 2. although the former is slightly higher than expected.…”

“…The enzymes measured in these studies and their corresponding genetic map positions are listed in Table 1. The assay conditions were as follows: AK-0.1 M glycine, 0.2 M KC1, 20 mM MgC12, 0.2 mM NADH, 10 mM ATP, 2 mM phosphoenolpyruvate, 20 mM arginine, 20 U/ml pyruvate kinase, 20 U/ml lactate dehydrogenase; CAT-0.1 M NaP04 (pH 7 4 , 20 mM H202; EST-6: 0.1 M NaP04 (pH 6 [16]. Expected levels of enzyme activity in trisomies were estimated from the parental contribution of chromosome arms.…”

“…Dosage compensation of X-linked genes may be considered as an evolutionary strategy required to equalize gene expression between individuals possessing different numbers of X chromosomes for sex determination [6,7]. In contrast, compensation in autosomal trisomies is not expected since the number of autosomes normally does not vary within a species.…”

Expression ofcis-regulatory mutations of thewhitelocus in metafemales ofDrosophila melanogaster

“…These and similar observations at other loci led to the concept that most genes on the X chromosome are doubled in expression per copy in the male, relative to the female. Numerous studies have addressed the problem of dosage compensation since that time (for review see Lucchesi, 1983;Lucchesi & Manning, 1987). Stern (1960) was the first to address experimentally the question of whether dosage compensation ex-tended to metafemales (3X; 2A).…”

“…Subsequently, the expression of X-linked genes in metafemales has been investigated by several individuals, with varying conclusions concerning whether compensation occurs depending on the type of analysis and treatment of the data. The majority of studies conclude that compensation does occur (see Lucchesi, 1983). Birchler et al (1989) re-examined the problem with standardization to DNA levels and found that the absolute expression of the X-linked genes was basically equivalent in total amount to diploid females but that autosomal gene expression was reduced.…”