I am interested in the relationship between gene dosage and the amount of protein expression. Any one has experience in this concern? If there is a consensus?
The strongest correlation will be with the strength of the promoter in pretty much any system. A low copy number plasmid with a strong promoter will make more protein than a high copy number plasmid with a weak promoter. This is true in microbial (bacterial) cells. In mammalian cells, expression can be amplified by gene duplication, and in the case of methotrexate amplification to produce a stable cell line. In this case, the protein expression can be more dependent on gene copy number, but not linearly correlated, and promoter strength still has a strong influence. Always start with promoter strength.
The gene product and even transcript can have a negative feedback loop which regulates the promoter strength so additional copies would be equally inhibited depending on the existing expression levels.
As I am not certain what the product is that you may be working on, my response may be a bit more general.
Gene dosage is the number of copies of a particular gene present in a genome. Gene dosage is related to the amount of gene product (proteins or functional RNAs) the cell is able to express. Since a gene acts as a template, the number of templates in the cell contributes to the amount of gene product able to be produced.
Generally speaking, more copies of a gene — or higher gene dosage — will result in increased expression of the proteins for which the genes code. However, this is not always the case, as some genes are regulated by other factors that affect their expression levels. For example, some genes are dosage-sensitive, meaning that changes in their copy number can have significant phenotypic consequences, such as diseases or developmental defects.
An example of a dosage-sensitive gene is HBB, which codes for the beta-subunit of hemoglobin. Humans normally have two copies of this gene, one from each parent. However, some people inherit a mutated version of this gene that causes sickle cell anemia, a blood disorder that affects the shape and function of red blood cells. People who have one normal and one mutated copy of HBB are carriers of sickle cell anemia, and they produce half normal and half abnormal hemoglobin. People who have two mutated copies of HBB have sickle cell anemia, and they produce mostly abnormal hemoglobin. Therefore, the amount of protein expression from HBB depends on the gene dosage and the type of alleles inherited.
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