Please indicate the section of this molecule in which mutations will have no eff

ID: 164182 • Letter: P

Question

Please indicate the section of this molecule in which mutations will have no effect on the protein that is produced. Explain your choice briefly.

In one mutated form of the gene producing this mRNA, the AGG starting at nucleotide 121 is now an ATG. This mutation leads to the complete absence of the protein. Please explain why this is so.

In one disease-producing form of this gene, the protein-coding sequence is completely normal, but there are about 1000 bp missing from the DNA just upstream of the region shown. How can it be that this mutation causes the same disease as do mutations in the protein-coding region?

1 ggcccgttaa gaagagcgtg gccggccgcg gccaccgctg gccccaggga aagccgagcg 61 gccaccgagc cggcagagac ccaccgagcg gcggcggagg gagcagcgcc ggggcgcacg 121 agggcaccAT Ggcccagacg cccgccttcg acaagcccaa agtagaactg catgtccacc 181 tagacggatc catcaagcct gaaaccatct tatactatgg caggaggaga gggatcgccc 241 tcccagctaa cacagcagag gggctgctga acgtcattgg catggacaag ccgctcaccc 301 ttccagactt cctggccaag tttgactact acatgcctgc tatcgcgggc tgccgggagg 361 ctatcaaaag gatcgcctat gagtttgtag agatgaaggc caaagagggc gtggtgtatg 421 tggaggtgcg gtacagtccg cacctgctgg ccaactccaa agtggagcca atcccctgga 481 accaggctga aggggacctc accccagacg aggtggtggc cctagtgggc cagggcctgc

Explanation / Answer

Please indicate the section of this molecule in which mutations will have no effect on the protein that is produced. Explain your choice briefly.

ATG is the initiation codon and protein will be start synthesized from this codon onwards, so if you make any deletion in 5’ upstream sequence to ATG, that will not going to have any effect on the protein produced. As from ATG onwards only your protein will be produced, so the deletion will not going to bring any change in the amino acid sequence of the protein. So protein will not be affected both structurally and functionally.

In one mutated form of the gene producing this mRNA, the AGG starting at nucleotide 121 is now an ATG. This mutation leads to the complete absence of the protein. Please explain why this is so.

You mentioned that at 121 position, the AGG has been mutated to ATG, in this scenario obviously the mutated ATG will try to act as initiation codon, and protein synthesis will be starting from this ATG, due to this the amino acid sequence produced from this reading frame will be entirely different from the normal protein amino acid sequence.

Mutated DNA:

atggcacc ATGgcccagacg cccgccttcg acaagcccaa agtagaactg catgtccacc tagacggatc catcaagcct gaaaccatct tatactatgg caggaggaga gggatcgccc

5'3' Frame 1

Met A P W P R R P P S T S P K Stop N C Met S T (Amino acid sequence)

Normal DNA:

ATGgcccagacg cccgccttcg acaagcccaa agtagaactg catgtccacc tagacggatc catcaagcct gaaaccatct tatactatgg caggaggaga gggatcgccc

Met A Q T P A F D K P K V E L H V H L D G S I K P E T I L Y Y G R R R G I A(Amino acid sequence)

If you see the amino acid sequence of these two above proteins, they are completely different as they started from different sites. So with the incorporation of ATG in AGG place, the protein was completely absent from the cell.

d)In one disease-producing form of this gene, the protein-coding sequence is completely normal, but there are about 1000 bp missing from the DNA just upstream of the region shown. How can it be that this mutation causes the same disease as do mutations in the protein-coding region?

It should be remembered that not only the protein coding region, even the region which lies upstream of the gene sequence is also important for the proper expression of that particular gene.

You mentioned that a deletion of 1000 bp upstream of gene sequence has resulted in the same disease; this clearly indicates that this upstream region which got deleted might be having enhancer region or cis-regulatory regions which are very important for the proper recognition of this specific gene by RNA polymerase to initiate the transcription process. In the absence of this region, the RNA polymerase will not be able to bind to this site and initiate the transcription process; you will not have the protein production. So deletion in this particular site has resulted in the same disease due to the absence of protein production.