Regulation of Gene Action — Dosage Compensation 



487 



That is, the system provides dosage com- 

 pensation with respect to some X-limited 

 loci. 8 



Note that in mammals parts of certain 

 chromosomes can become more or less per- 

 manently fixed in their functioning. 9 The 

 mosaicism just discussed in mice results in 

 patches of tissue of different phenotypes. 

 When a chromosome segment is function- 

 ally turned off (or on) in a given cell, the 

 descendant cells are similarly turned off (or 

 on), despite the intervening occurrence of 

 mitosis. Consequently, the result is a patch 

 of tissue of similar phenotype. This turn- 

 ing off occurs more than a week after fer- 

 tilization in mice and, as mentioned, in 

 human beings. Moreover, it at least some- 

 times fails to occur in the germ line. For 

 example, 1 " although one X in an adult fe- 

 male rat is hyperpycnotic in somatic tissues, 

 the XX-bivalent in the oocyte is isopycnotic; 

 that is, both members stain similarly. It 

 is therefore hypothesized 1T that a gene can 

 exist in two functional forms, active or in- 

 active, and that one form will persist despite 

 intervening nuclear divisions until specific 

 conversion to the other. For some maize 

 genes, it is found that a given state during 

 gametogenesis is continued in the zygote. 

 In the endosperm, for example, a maternally- 

 derived gene has been found to continue 

 activity whereas the paternally-derived allele 

 is inactive. 



Drosophila 



In Drosophila, as in man, typical males have 

 one X chromosome and typical females two. 

 Many of the X chromosome loci have es- 

 sentially the same phenotypic effect in males 

 as in females; that is, many loci show dos- 



s See M. F. Lyon (1962). 



9 See also R. DeMars (1963). 



10 See S. Ohno. W. D. Kaplan, and R. Kinosita 

 (1960). 



11 By M. Lyon and by D. Schwartz. 



age compensation. Thus, the eye color of 

 the apr Y male and apr/apr female is es- 

 sentially identical. Dosage compensation 

 applies not only to hypomorphic mutants 

 (p. 194) like apricot but also to their wild- 

 type alleles. Consequently, both wild-type 

 males and females have, for example, the 

 same dull-red eye color. Other X chromo- 

 some loci in D. melanogaster showing dos- 

 age compensation are y; ac; sc; sn; g; f; and 

 B. Only partially compensated for, how- 

 ever, is fa, since females show somewhat 

 more effect than males. Hw (hairy wing), 

 w e (eosin), and W (ivory) show no com- 

 pensation, nor do any autosomal genes, nor 

 bb which has a locus in both the X and the 

 Y chromosomes and, therefore, is usually 

 present in paired condition in both males 

 and females. 



The cytological basis for dosage compen- 

 sation is difficult to study in ordinary so- 

 matic cells of Drosophila because of the 

 small size of diploid nuclei. Since the so- 

 matically synapsed polynemic X's in the fe- 

 male larval salivary gland and other nuclei 

 appear identical, dosage compensation in 

 Drosophila does not seem to be based upon 

 differences in chromosome coiling between 

 homologs. Perhaps this means that the 

 alleles on both X chromosomes of a fe- 

 male are equally functional, and that in 

 Drosophila dosage compensation is accom- 

 plished by a somewhat different mechanism 

 than it is in mammals. Whereas the single 

 X and the paired X's in salivary cells of 

 males and females have DNA in approxi- 

 mately a one-to-two ratio as expected, the 

 single X seems to contain just about as 

 much RNA and protein as the double X. 

 Dosage compensation therefore involves the 

 "stepping-up" of gene action by single X's, 

 the suppression of gene action by double 

 X's, or both. A number of genetic studies 

 throw some light upon dosage compensa- 

 tion in Drosophila. and their results can be 



