X-chromosome have been demonstrated to confer a bias towards inactivation for the chromosome on which they sit. Truly random X-inactivation may also appear to be non-random if one X-chromosome carries a deleterious mutation. This can result in fewer cells which express the lower-fitness X-chromosome to be present in the body as these cells are selected against. Two-fold increased transcription of a single ♂ X Another mechanism common for achieving equal X-related genetic expression between males and females involves two-fold increased transcription of a single male X chromosome. Thus, heterogametic male organisms with one X chromosome may match the level of expression achieved in homogametic females with two active X chromosomes. This mechanism is observed in Drosophila. The concept of dosage compensation actually originated from an understanding of organisms in which males upregulated X-linked genes two-fold, and was much later extended to account for the observation of the once mysterious Barr bodies. As early as 1932, H.J. Muller carried out a set of experiments which allowed him to track the expression of eye color in flies, which is an X-linked gene. Muller introduced a mutant gene that caused loss of pigmentation in fly eyes, and subsequently noted that males with only one copy of the mutant gene had similar pigmentation to females with two copies of the mutant gene. This led Muller to coin the phrase “dosage compensation” to describe the observed phenomenon of gene expression equalization. Despite these advances, it was not until Ardhendu Mukherjee and W. Beermann performed more advanced autoradiography experiments in 1965 that scientists could confirm that transcription of genes in the single male X chromosome was double that observed in the two female X chromosomes. Mukherjee and Beermann confirmed this by designing a cellular autoradiography experiment that allowed them to visualize incorporation of into ribonucleic acid of the X chromosomes. Their studies showed equal levels of incorporation in the single male X chromosome and the two female X chromosomes. Thus, the investigators concluded that the two-fold increase in the rate of RNA synthesis in the X chromosome of the male relative to those of the female could account for Muller's hypothesized dosage compensation. In the case of two-fold increased transcription of a single male X chromosome, there is no use for a Barr body, and the male organism must use different genetic machinery to increase the transcriptional output of their single X chromosome. It is common