We describe here the results of a search of Mendelian inheritance in man, GENDIAG and other sources which suggest that, in comparison with autosomes 1, 2, 3, 4 and 11, the X chromosome may contain a significantly higher number of sex- and reproduction-related (SRR) genes. A similar comparison between X-linked entries and a subset of randomly chosen entries from the remaining autosomes also indicates an excess of genes on the X chromosome with one or more mutations affecting sex determination (e.g. DAX1), sexual differentiation (e.g. androgen receptor) or reproduction (e.g. POF1). A possible reason for disproportionate occurrence of such genes on the X chromosome could be that, during evolution, the 'choice' of a particular pair of homomorphic chromosomes for specialization as sex chromosomes may be related to the number of such genes initially present in it or, since sex determination and sexual dimorphism are often gene dose-dependent processes, the number of such genes necessary to be regulated in a dose-dependent manner. Further analysis of these data shows that XAR, the region which has been added on to the short arm of the X chromosome subsequent to eutherian-marsupial divergence, has nearly as high a proportion of SRR genes as XCR, the conserved region of the X chromosome. These observations are consistent with current hypotheses on the evolution of sexually antagonistic traits on sex chromosomes and suggest that both XCR and XAR may have accumulated SRR traits relatively rapidly because of X linkage.
We have reported that production and characterization of antibodies highly specific to 5-methyl-cytosine (SmC) and the development of a sensitive immunochemicai method for the detection of 5mC in DNA [EBBS Lett. (1982) 150, 4691. Extension of this method to two other modified bases, 6-m~hyladenine (6mA) and %methyiguanine (7mG), is reported here. By use of this immunochemical approach, we are able to detect 5mC, 6mA and 7mG in human and Drosophila DNA and confirm their presence in the DNA of two mealybug species.
DNA methylation Biotin-avidin cross-linking DNA-protein interaction Z-DNA X-chromosome inactivationGene regulation
We have previously reported a sensitive immunochemical method for detecting 5‐methylcytosine in DNA which involves spotting DNA samples on nitrocellulose paper and detection of 5‐methylcytosine, if any, by a combination of the double antibody method and a staining reaction brought about by biotin‐avidin and peroxidase. We report here a linear relationship between the concentration of 5‐methylcytosine in DNA and staining intensity, as recorded by photoacoustic spectroscopy. It appears possible to obtain, by this method, reliable quantitative estimates of 5‐methylcytosine in nanogram quantities of intact DNA. When Drosophila melanogaster DNA was assayed for the presence of 5‐methylcytosine by this method, a faint but clearly positive reaction was obtained. When the photoacoustic intensity of this stained spot is compared with a calibration plot derived from phi X174 DNA whose 5‐methylcytosine content is known, we obtain, for D. melanogaster DNA, one 5‐methylcytosine residue in approximately 12 500 bases or 0.008 mol% methylation.
In mealybugs, chromatin condensation is related to both genomic imprinting and sex determination. The paternal chromosomal complement is condensed and genetically inactive in sons but not in daughters. During a study of chromatin organization in Planococcus lilacinus, digestion with micrococcal nuclease showed that 3% to 5% of the male genome is resistant to the enzyme. This Nuclease Resistant Chromatin (NRC) apparently has a nucleosomal organization. Southern hybridization of genomic DNA suggests that NRC sequences are present in both sexes and occur throughout the genome. Cloned NRC DNA is A+T-rich with stretches of adenines similar to those present in mouse alpha-satellite sequences. NRC DNA also contains sequence motifs that are typically associated with the nuclear matrix. Salt-fractionation experiments showed that NRC sequences are matrix associated. These observations are discussed in relation to the unusual cytological features of mealybug chromosomes, including the possible existence of multiple centres of inactivation.
In female mammals, one of the two X chromosomes present is inactivated during early development. In marsupials, the paternal X is inactivated; in eutherians, one of the two X chromosomes is inactivated at random. A mechanism is proposed to explain the cytogenetic data on inactivation and the derivation of the eutherian system from the marsupial system. In the marsupial system, a site on the X chromosome is sensitive to paternal origin: when the X chromosome is of maternal origin, this sensitive site is responsible for influencing an adjacent site, the receptor, to maintain the X in an active state; the paternal X becomes inactive. Transposition of the sensitive site to an autosome in eutherians would have two consequences. Since the receptor site of the X chromosome is no longer adjacent, the autosomal sensitive site of maternal origin would activate an X at random. The number of active X chromosomes would conform to the number of maternal sensitive sites and thus, generally, to the number of maternal sets of autosomes. The response of the sensitive site to its passage through the male may be designated as imprinting, a term used by Crouse to indicate that the behavior of Sciara chromosomes is determined by parental origin.
The evolutionary function of X chromosome inactivation is thought to be dosage compensation. However, there is, at present, little evidence to suggest that most X chromosome-linked genes require such compensation. Another view-that X chromosome inactivation may be related to sex determination-is examined here. Consider a hypothetical DNA sequence regulating a major structura gene concerned with the determination of maleness. If this regulatory sequence occurs in both X and Y chromosomes and if its copy number in the Y chromosome is sgnificanly greater than in the X chromosome, then the male-determining properties of the Y chromosome could be attributed to this higher copy number.
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