Dose compensation

In vivo analysis is characterized by limitations in radiation dose, compensated by large samples and large detectors. For the measurement of whole-body composition NAA has been accepted as a reference method by which other methods can be assessed [16]. 

The dose compensation is an example where the gene interaction in the regulation of the nonribosomal RNA synthesis was demonstrated for various animals and especially Drosophila. 

The second hypothesis on the phenomenon of dose compensation was suggested by Goldschmidt. This hypothesis rejected the presence of specific compensatory gene modifiers and explained dose compensation through physiological peculiarities in male development as compared with female development (Goldschmidt, 1961). 

Therefore, at the present time the actual data do not allow the unreserved acceptance of either the gene-compensator hypothesis or Goldschmidt s physiological hypothesis as a complete explanation for dose-compensation mechanisms. 

Concommitantly, the possibility of casting some light on the nature of this phenomenon has appeared in connection with progress in the development of biochemical and cytological methods of investigation. First of all, at what level does dose compensation take place, transcriptional or post-transcriptional ... 

Korge (1970b) demonstrated that the dose compensation (the 3B puff of Df(l)w y/ strain D. melanogaster was chosen as an experimental niodel) or the dose effect (duplication in female and male) occurs on the transcriptional level (Fig. 14). Although direct comparison was not possible, there is good correlation between the RNA synthesis and the phenotypic expression in the case of the dose compensation as well as in the case of the dose effect, when the trait expression is associated with the gene number. Two results represented the special interest ... 

The same chromosomal segment -3B puff in some cases can demonstrate dose compensation [in the Df(l)w ", flies] whereas in other cases it exhibits the dose effect [in ywbb Dp(l 3) flies]. 

The change in position of any part of the chromosome in the genome (for instance, the transfer of an autosomal segment from chromosome 3 to the X chromosome) does not change the dose compensation or the dose effect at the level of direct phenotypic expression or at the transcriptional level of RNA synthesis (Lakhotia, 1970). 

Fig. 14. Dose compensation and dose effect on the level of the RNA synthesis in small segment of X chromosome and in autosome 3, autoradiographic method. Open bars, normal activity striped bars, dose effect stippled bars, dose compensation. (After Korge, 1970 b)...

Therefore, dose compensation is determined by differences in the transcriptional activity of the X chromosome in the male and female and is an example of the well-proven regulation of gene activity in animals. This regulation is apparent in the synthesis on only a certain amount of RNA. Various parts of the chromosome have demonstrated a kind of autonomy in this respect. 

These data are in good agreement with data on the activity of 6-phosphoglu-conate dehydrogenase from the same individuals (Fig. 15). Therefore, in the case of dose compensation, the correlation between transcriptional activity and the biochemical expression of the trait was strictly demonstrated (Faizullin and Gvozdev, 1973). 

An interesting consideration was expressed by Holmquist (1972). Holmquist determined that up to 100% of dosage compensation, on the phenotypic level of gene expression (e.g., enzyme activity) in D. melanogaster, corresponded to only 40% of the transcription rate increase in the male X chromosome as compared to the female. Thus, two possible mechanisms for dose compensation were suggested ... 

There have been some genetic data which have corroborated the presence of regulatory sites in X-chromosomal loci. The mutation apricot (w ) of the white gene demonstrated the ability for dose compensation, hence the eye color of males X " Y and females X X is the same. Another mutation, eosin (w ), of the gene white does not demonstrate the dose compensation effect. Thus, the eye color of X " X " females is twice as dark as that found in Y males. These two mutations,... 

Finally, some data (Holmquist, 1972) have shown that, on the phenotypic level of dose compensation, post-transcriptional processes are also important. 

There are few actual experimental data concerning the transcriptional level of gene action regulation and these data are restricted, in general, by observations of the dose compensation mechanism (see above). 

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