RootsWeb: GENEALOGY-DNA-L Re: [DNA] Molecular clocks: when times are a-changin': reply part 1

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Archiver > GENEALOGY-DNA > 2006-11 > 1162609283

From: "John McEwan" <>
Subject: Re: [DNA] Molecular clocks: when times are a-changin': reply part 1
Date: Sat, 4 Nov 2006 16:01:23 +1300
In-Reply-To: <000c01c6ff98$b48673a0$6400a8c0@Ken1>

Ken said .... a buzz word term like "purifying selection" .... It is no more a buzz word than using SNP or STR, use google search http://en.wikipedia.org/wiki/Stabilizing_selection Stabilizing selection, also known as purifying selection or negative selection, is a type of natural selection in which genetic diversity decreases as the population stabilizes on a particular trait value. Put another way, extreme values of the character are selected against. This is probably the most common mechanism of action for natural selection. Than Ken said ..... You can't drag in "selection" as a factor without spelling out what might be selected for in the length of these STRs? More explanations please! .... Variation in STR length both within and outside of protein coding regions has been recorded in the published literature as being associated with disease i.e. detrimental effects that purifying selection eliminates. People cannot continuously claim on this list that variation in STR length is entirely neutral in evolutionary terms as they commonly do. It's a common assumption, and it may be close to the truth in the majority of cases, but restating an assumption ad nauseum as John Chandler has done on this list does not make it true. I am being direct here because I know this has been explicitly raised on this list previously several times and he was a correspondent. For an example of a STR affecting disease within a protein coding region http://en.wikipedia.org/wiki/Huntington's_disease and http://en.wikipedia.org/wiki/Trinucleotide_repeat_disorders records 14 such instances discovered to date. For an STR outside a protein coding region causing disease there is a SCA12 CAG expansion in a 3'UTR (aka non coding region) http://www.geneclinics.org/servlet/access?id=8888890&key=siICL-FRh9RL8&g ry=INSERTGRY&fcn=y&fw=t064&filename=/profiles/sca12/index.html Friedreich's ataxia is cased by an STR within an intron (i.e. non coding and not in the final mRNA). In fact it fits John Chandler definition of junk DNA and is an example of it having an effect on fitness LOL..... :-) http://en.wikipedia.org/wiki/Friedreich%27s_ataxia There are others as well and my guess is there are many many that are as yet not discovered. The examples presented are extreme cases where the selection intensity is obviously very high (i.e. variation in length results in disease and affected people have fewer progeny that reach maturity). In the majority of cases, however, selection pressure on variants at other loci may be much much lower perhaps only 1% or less decline in fitness and existing technology will struggle to measure it. In many cases the effect may be so small as to be effectively zero. However, you cannot assume that variation in the Y STRs or variation in length outside certain bounds in these STRs does not have effects that are significant in evolutionary terms (i.e. over 100 to 1000s of generations). This is especially pertinent when there is an intense debate about a decline in mutation rate estimates (both SNP and STR) when measured over longer time periods, and the authors in refereed literature discussing this problem have also explicitly referred to this as a possible contributing factor. John McEwan