conservative vs semi conservative substitution

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conservative vs semi conservative substitution

Postby Niroula » Sep 08 2009 3:40 pm

Dear All,
what is the difference between conservative and semi conservative substitution. I confuse when I analyzed[color=#0000BF]
my amino acid sequence. Could any one help me to distinguish the two terms.And how they work in protein functions?
Cheers
Raj Kumar Niroula[/color]
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Re: conservative vs semi conservative substitution

Postby Iwantcrts » Sep 08 2009 4:58 pm

I have not heard of this distinction. the only distinctions I know of are conserved, similar and non conserved. Where in "similar" amino acid as as it sounds, similar with respect to the amino acids properties; size, charge of the functional (R) group, and the polarity of the amino acids. While non-soncerved substitutions are when an amino acid is replaced with another that has vastly different properties, such as a glycine to tryptophan substitution.

I wouldnt place too much emphasis on these terms instead focus on what the changes mean in the real world. i.e. has an amino acid located in/around the active site or a defined structure changed, what is this change and how might it affect your proteins structure/function/stability. It is important to remember that although bioinformatic analysis is a useful tool, it can not be used to answer specific questions. But, it can be used to generate hypothesis that are then tested in the lab.

I just realised a "conservative" sunstitution may be a silent mutation, i.e. a point mutation that changes the tRNA codon used, but the amino acid encoded within the translated polypetide remains the same. This is also known as third base wobble. So that may give a distinction, conservative: codon used changes but amino acids stays the same, semi-conservative: Amino acid replaced with another, similar amino acid, and then there is the non-conserved substitution.
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Re: conservative vs semi conservative substitution

Postby mchlbrmn » Sep 09 2009 4:33 pm

It seems people do use this term to refer to actual amino acid substitutions.
I found the quote below at this link:
https://lists.sdsc.edu/pipermail/pdb-l/ ... 02259.html
"conservative amino acid substitution" is not a well-defined term,
though the different usages are usually fairly close.

One common operational definition is that the substitution matrix for
the pair of residues has a positive value. This, of course, depends
on what substitution matrix one uses, and is not really very useful
when other methods for regularizing amino acid distributions are used.

Still, since the concept is of dividing substitutions into
conservative and non-conservative is inherently imposing a binary
classification on a more continuous space, you aren't going to be able
to get a perfect answer, and picking the positive pairs out of
BLOSUM50 is as good a choice as any.
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Re: conservative vs semi conservative substitution

Postby Vtheroux » Jun 01 2018 6:21 pm

I am not a molecular biologist. i am an occupational therapist trying to understand how semi conservative vs nonconservative amino acid substitutions play out in genetic phenotypes. My son has an unknown GGG>TGG substitution on the PNKD gene (exon 7) This has not been documented anywhere in the world and it was cited as a semi-conservative substitution (G252W). Phenotype is that of a child with cerebral palsy -no known organic brain damage, just this odd substitution that has never been reported. Though I am generally medically literate, these minute details about how amino acid substitutions manifest are beyond my understanding. His geneticist, nor neurologist can not understand nor explain what it means either, except its "probably not good/deleterous"

I was struck by your glycine > tryptophan comment, citing this as a non-conservative substitution.
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Re: conservative vs semi conservative substitution

Postby r.rosati » Jun 06 2018 10:22 pm

Vtheroux wrote:I am not a molecular biologist. i am an occupational therapist trying to understand how semi conservative vs nonconservative amino acid substitutions play out in genetic phenotypes. My son has an unknown GGG>TGG substitution on the PNKD gene (exon 7) This has not been documented anywhere in the world and it was cited as a semi-conservative substitution (G252W). Phenotype is that of a child with cerebral palsy -no known organic brain damage, just this odd substitution that has never been reported. Though I am generally medically literate, these minute details about how amino acid substitutions manifest are beyond my understanding. His geneticist, nor neurologist can not understand nor explain what it means either, except its "probably not good/deleterous"

I was struck by your glycine > tryptophan comment, citing this as a non-conservative substitution.


Hello,
it's actually not easy to comment, especially within a diagnostic standpoint, about variants that have never been described before and are not openly destroying the protein's function. Is this variant homozygous, or is it heterozygous in your child? If it's heterozygous, is it "de novo" (i.e. none of you parents have it)?
If it's heterozygous and de novo, or homozygous and inherited (but unknown so far), then yes, there is a relatively strong possibility that it might be disease-causing.
Unfortunately, the gene has not been linked specifically to cerebral palsy so far, so that's an even broader question than whether the variant is impacting or not on the function of the protein. However, this might indeed be a convincing candidate.
If I might ask: is your question coming from a doubt that this might be a good lead?
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