Under the assumption that sites under positive selection are more tolerant to mutations, can one interpret (assume) the intolerant sites to not be under positive selection?
The assumption in the query sounds backwards to me. If a gene is normally important for a cell to grow well and the gene is disrupted by insertion then the cell is expected to grow less well.
Thanks. This scenario should be true for essential genes which are usually intolerant to mutations. Sites under positive selection are in the process of acquiring changes to accomodate new functionality. Given this they may tolerate mutations. Is this valid argument ?
No. Here's why: The way the question is framed conflates (mixes together) two different types of mutations that have different consequences. Point mutations change a base that changes an amino acid and may lead to a protein with an altered function. Insertional mutagenesis typically makes a null allele of the gene into which the insertion is done. In the insertional case (as it is typically done in screens) the gene is "knocked out". The insertion allele is the phenotypic equivalent of a full deletion allele.
Your way of thinking about it is very original. Genetics is a vast field and I would not be surprised if there are specific cases that match your idea but they will be rare.
you are welcome. good luck in your work!
ps: when you say "...essential genes which are usually intolerant to mutations." This is exactly where it gets confusing. Many essential genes are tolerant of point mutations but are not tolerant of insertion mutations. The example I know best is E. coli RpoB for which there are about 40 point mutations that render rifampacin resistance. But the gene is essential for E. coli and is not tolerant of insertion mutations.
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