Thoughts About 16519??

[vineviz]

Also, I'm not sure about the comment "markers mutate individually." As an example, my K1c2 requires three coding-region mutations plus 16320T. So either those four happened at the same time, or about the same, or any haplotypes with only, say, two of those together didn't survive. 16320T does show up in other subclades, but not, to my knowledge, the coding-region mutations.

You've supplied your own explanation, Bill. The lines without all four have either died out or simply haven't been tested yet.

The number of full genome mtDNA sequences is pretty low, and with more testing the phylogeny is bound to become better sorted. Even mtDNA phylogenies published just a few years ago are often out-of-date.

[vineviz]

First of all, I've never like to hear 16519C called a "hotspot." The original K, for example, had 16519C, I believe, and virtually every K since has had it. A couple of members of the K Project have had a back mutation there, but so far I've never seen a cluster formed from those without it. To me, hotspots would be heteroplasmic mutations like 16093C or 309.1C where we see siblings differing.

Despite its apparent stability in some haplogroups, across many haplogroups 16519 is certainly one of the most frequently mutating positions. It rivals the frequency of insertions and deletions in the 522-524 region of HVR2.

http://www.cstl.nist.gov/div831/strbase//pub_pres/Coble_IJLM2004.pdf

[GregKiroKH2]

So it has been claimed that there are numerous T to C mutation hot spots in mammalian mitochondrial DNA?

The high amount of homoplasy in mitochondrial DNA could therefore be due to the phylogenetic noise introduced by mutation hot spots. . . . The high mutability of guanines, however, cannot explain all the hypervariability observed in humans: Some of the detected hot spots involve numerous T C or A G changes within H. sapiens and several changes between species. These sites might be unconditional, bidirectional hot spots.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1361717

http://www.genome.org/cgi/content/full/16/2/215

Animal mitochondrial DNA is characterized by a remarkably high level of within-species homoplasy, that is, phylogenetic incongruence between sites of the molecule. . . . we test the hot spot hypothesis by comparing patterns of site-specific polymorphism and divergence in several groups of closely related species, including hominids. We detect significant co-occurrence of synonymous polymorphisms among closely related species in various mammalian groups, and a correlation between the site-specific levels of variability within humans (on one hand) and between Hominoidea species (on the other hand), indicating that mutation hot spots actually exist in mammalian mitochondrial coding regions. . . . This study provides a plausible mutation model that potentially accounts for the peculiar distribution of mitochondrial sequence variation in mammals without the need for invoking recombination. It also gives hints about the proximal causes of mitochondrial site-specific hypermutability in humans.

A hot spot is a marker that is prone to frequent (or recurrent) mutations.

[PDHOTLEN]

I got one of those 16519's too

My full sequence results were enlightning, if for no other reason than to expose many differences from the rest of you deep in my mitochondrial DNA. There sure wasn't much of a hint of that difference in my HVR1.

My HVR1 is 16519 & 16270. But since I am U5b2, it shows a parallelism with haplogroup H. In other words: back-mutation. Anyway, 16519 should not be dismissed out of hand, as a meaningful marker, in my opinion. It shows a separate branching within my haplogroup, if nothing else. And since I don't know much about my maternal line from normal genealogical methods, this scientific result of my mtDNA is to me potentially significant.

[GregKiroKH2]

Not Pyrimidine to Purine????

But why is it a pyrimidine change?

[PDHOTLEN]

me again (re 16519)

I bookmarked one of you peoples' recommended websites:

http://www.genpat.uu.se/mtDB/

It works best if you have your complete mtDNA spectrum along side, while you're browsing. I was able to narrow down their geographical locations better. But their database is woefully incomplete. According to them, I muust come from Sardinian female stock.

I am U5b2 WITh 16519C. But their U5's with that mutation (in Sardinia yet!) exclude U5b2 as not having it. They (Fraumene, et al.) show their new U5b3 with it, as if U5b2 is supposed not to have 16519C. But you must look at the Fraumene paper to see the haplo-sub-groups.

There is one lonesome HVR1 in England who has the same HVR1 as myself (16270T & 16519C). I sure wish that person would upgrade their mtDNA testing!

[GregKiroKH2]

The 16519C mutation follow statistical patterns:

Control region rates follow a negative binomial distribution (gamma distribution).
Most sites -invariant
Few sites -fast

High α(low variation)
Low α(high variation)

The SHAPE of the curve α is inversely related to the amount of heterogeneity
Yang, 1996

[Jim Denning]

16519C is seen on trade routes,
Halgason’s Study
and it is a hot spot in many haplogroups such as I, X, T, K, U3, and U4.
16519T is seen in haplogroups such as U5, J, and T
Haplogroup group H was evenly split between 16519C and T.
Helgason A, Sigurðardóttir S, Gulcher JR, Ward R, Stefánsson
K (2000) mtDNA and the origin of the Icelanders: deciphering
signals of recent population history. Am J Hum Genet 66:999-
1016.

The L1c people from Kikuyu (Kenya) might have some 519 people but the other article did not say if they are T or C.

i THINK OF HRV NUMBERS AS ROADS
some female started her trip on the 519 interstate and took several roads to get to where we are now. on the chart is her road trip map.
our job is to see where 519 was when that person was there think of the staircases in harry potter that move these would be interdemensional since my 519 might be in ireland my wifes might be in italy

[Jim Denning]

I am not sure. After all, I am kicking around some ideas . . . I wrote some informal papers on type one and type two muscles. The idea of having to escape wild animals like the saber tooth tiger or adapting to new climate conditions have fascinated me in the past. Muscle and brain development is very important to the mtDNA. So, environmental conditions dictate survival. If one does not have the needed survival skills, then the individual will not reproduce, right or wrong has nothing to do with it. Mitomap has a good write up on adaptive ancient mtDNA. Also, the Ruiz-Pesini et al. 2004:226 article mentions it too. The research in the literature might suggest that some alleles are more adaptive in humans than other alleles in humans. So, how is human mtDNA different from plant mtDNA and such?

i imagine we never were in the race until we developed things like clovis and team hunting saber tooth vs one human is a loser but 15 humans with clovis points is a different matter.i would guess teams & weapons came before muscle changes in development had time to form

[GregKiroKH2]

Stochastic vs. Adaptive Polymorphism

Trade routes seem to suggest more of a stochastic mutation mechanism for 16519 than the adaptive polymorphism mechanism climate type change everyone talks about . . .

In fact, codon bias is more extreme in highly-expressed genes than in rarely-transcribed genes (where it is weak to non-existent). In addition, codon bias (at least in humans) in more extreme in 3rd position GC-rich genes than in AT-rich genes. Finally, the pattern of codon bias is species-specific
selection-mutation-drift hypothesis. Here, selection for optimal codons is balanced by the effects of mutation and drift allowing persistence of non-optimal codons
If recombination is sufficiently rare in this region, these hitchhiking alleles can actually become fixed along with the advantageous allele at the selected locus.
Dispersed repeated sequences are spread throughout the genome, and represent transposable elements (SINEs and LINEs)
variable number of tandem repeat (VNTR) loci as they typically show high levels of variation in repeat number among chromatid copies. VNTR loci (particularly SSRs) show extermely high mutation rates
http://bioweb.wku.edu/faculty/McElro.../524lects5.htm

i THINK OF HRV NUMBERS AS ROADS
some female started her trip on the 519 interstate and took several roads to get to where we are now. on the chart is her road trip map.
our job is to see where 519 was when that person was there think of the staircases in harry potter that move these would be interdemensional since my 519 might be in ireland my wifes might be in italy

[GregKiroKH2]

Kimura argued that the level of genetic variation present in natural populations could not be maintained by selection. I do not know what he would say about 16519 thou. Still, under this model, polymorphism is transient and stochastic, and differences in allele frequency among populations need not be adaptive. And so does 16519. By the way, those who could not run away and steal food from the saber tooth tiger might have been eaten. They needed the muscles to run. When this behavior entered into the tribal domains, running away was not as important as bartering a trade to escape tribal justice. The saber tooth tiger had the right idea, but they did not survival their hard line approach. And 16519 just does not seem to fit into some populations.

So, do bacteria have a memory?

i imagine we never were in the race until we developed things like clovis and team hunting saber tooth vs one human is a loser but 15 humans with clovis points is a different matter.i would guess teams & weapons came before muscle changes in development had time to form

[Jim Denning]

Kimura argued that the level of genetic variation present in natural populations could not be maintained by selection. I do not know what he would say about 16519 thou. Still, under this model, polymorphism is transient and stochastic, and differences in allele frequency among populations need not be adaptive. And so does 16519. By the way, those who could not run away and steal food from the saber tooth tiger might have been eaten. They needed the muscles to run. When this behavior entered into the tribal domains, running away was not as important as bartering a trade to escape tribal justice. The saber tooth tiger had the right idea, but they did not survival their hard line approach. And 16519 just does not seem to fit into some populations.

So, do bacteria have a memory?

please understand i am mixed dominant [au contraire]
thats why i am like i am

that said how did we grow the muscles to go fast did we lose enough humans to survive sabers were we bunnies mass poducing saying we need more kids so we can feed the saber long enough to get the mucsles to change so we could beat him? hmm.

bacteria sure they have something you might call instinct . why because they remember the way to infect. they dont get inside you and say what are we doing here? zing they zip to the best place to kill you

now compare that to the saber did we stop the saber meals when evolution gave us muscles faster then the bacteria knew to find the right spot.
this is like those treees with the seeds that you canslpit and put on your nose. how long did the tree drop seeds straight down until it knew it needed wings? questions ,questions ,questions ,questions ,?


we all need to remember that this mtdna is women who could of been slaves or daughter sold to slavery or as wives to travelers. hookers following the gold rushes or trade routes looking for merchants with cash. wives of soldiers.women stolen in raids.
again i think the best approach is small area studies i think these will find the clusters of 519 take a look at the frosinone study .one of mine seems 519 is a strong number there this area is alot of small farming villages on the sides of hills and vast intermarring in these towns so alot of the same mtdna lines with the same basic numbers

[GregKiroKH2]

I liked reading about the Saber Tooth Tiger so much when I was younger. I brought a giant poster of a cartoon one. Some types of bacteria and the Saber Tooth Tiger interact with humans harshly. Maybe, they did not influence 16519 mutation, but it is interesting to think what those tiger teeth could do which could be the same result as bacteria entering a cell.

When ROS production exceeds the capacity of detoxification and repair pathways, oxidative damage to protein, DNA, and phospholipid occurs, disrupting mitochondrial oxidative phosphorylation and leading to cell damage and death. . . . Here we have investigated how a series of exogenous ubiquinone analogs interact with oxidative phosphorylation and with ROS metabolism.
http://www.jbc.org/cgi/content/full/280/22/21295

please understand i am mixed dominant [au contraire]
thats why i am like i am

that said how did we grow the muscles to go fast did we lose enough humans to survive sabers were we bunnies mass poducing saying we need more kids so we can feed the saber long enough to get the mucsles to change so we could beat him? hmm.

bacteria sure they have something you might call instinct . why because they remember the way to infect. they dont get inside you and say what are we doing here? zing they zip to the best place to kill you

now compare that to the saber did we stop the saber meals when evolution gave us muscles faster then the bacteria knew to find the right spot.
this is like those treees with the seeds that you canslpit and put on your nose. how long did the tree drop seeds straight down until it knew it needed wings? questions ,questions ,questions ,questions ,?


we all need to remember that this mtdna is women who could of been slaves or daughter sold to slavery or as wives to travelers. hookers following the gold rushes or trade routes looking for merchants with cash. wives of soldiers.women stolen in raids.
again i think the best approach is small area studies i think these will find the clusters of 519 take a look at the frosinone study .one of mine seems 519 is a strong number there this area is alot of small farming villages on the sides of hills and vast intermarring in these towns so alot of the same mtdna lines with the same basic numbers

[jan]

GregKiroKH2:

the hotspots (16519, 309.1 and 315.1, deletions around 522) are not related to each other, they can happen in any combination in any haplogroup.

And I had never heard of 16223 as a neanderthal marker. 16233 is the ancestral state. It is in the Western Eurasian lineages that 16233 mutated.



cacio

Could you explain what you mean here, because I have seen the 16233 mutation in L2b lineages as well.

[cacio]

jan:

I meant 16223, not 16233. 16223 is the ancestral state because it is found in all haplogroups except the R descendants.

cacio