In the genome there is a gene (called Gene A) containing no open-reading frame and thus does not code for a protein. However, the RNA synthesis from this gene is abundant and easily detectable in all cells of any type. A survey of its sequence suggests that it is apparently present in multiple similar copies in normal cells. There are sequences similar to but not identical to TATA-box and CAAT-box upstream of its transcription start site. When researchers introduced a mutation to remove these TATA and CAAT boxes and substitute them with other unrelated sequences, there was little effect on the transcription of this gene. When researchers removed a sequence GC-rich box located about 20 bases downstream of the transcription start site of this gene, the transcription was not reduced either. Various other short 10-20 bp deletions downstream of the transcription start site did not affect transcription of gene A either. However when a large segment of this gene was deleted the RNA, although detectable, became unstable. The researchers tried to find if this gene was the only one of its kind or if there are many more such genes hidden in our genome. To their surprise they found that there were several copies of this gene in the human genome, running into hundreds (we consider an assumed number of 100 in this case). All these copies, non-identical yet highly similar in sequence, were present on multiple chromosomes. Interestingly, the multiple copies of Gene A from various chromosomes exhibited spatiotemporal co-localization in a large region of the nuclei. In hypothetical experiments and computer-aided simulations, researchers deleted 50 of the 100 copies of gene A. The cells with 50 copies of gene A deleted barely survived, could not respond to stimuli, were unable to carry out mitosis and died after some time. A team of scientists tried to increase the transcription from the remaining 50 copies of gene A to compensate for the lost 50 copies by simply increasing the activity of the RNA polymerase 2-complex. They tried manipulating the expression by increasing the concentrations of RNA Polymerase 2-complex and found no effect. Increasing cytosine methylation however reduced the Gene A transcript levels to near zero and rapidly killed the cells. However, without changing the RNA Polymerase 2 or cytosine methylation, if they removed the repressive histone marks, they could rescue the effects of loss of Gene A copies partially and the cells (with 50 copies depleted) survived better. By using advanced experiments and simulations, it was established that in the absence of Gene A product the amino acids remain unpolymerized and protein synthesis was adversely affected.
