Message 391 of 467 (785423) 06-04-2016 3:09 PM

Reply to: Message 387 by AZPaul3 05-05-2016 5:00 PM

(geezer mode) Or it could be that the old stuff that is still around is good music and most new stuff is terrible. Survival of the fittest in action.

Message 392 of 467 (785435) 06-05-2016 2:57 AM

Reply to: Message 390 by caffeine 06-04-2016 1:47 PM

There are about 100 mitochondria in a human cell. Suppose they were all different (they won't be, that's what we're trying to explain, but suppose they were). They (approximately) double in number and then the cell divides. But there's no reason why each daughter cell should get one copy of each distinct mitochondrion. (Unlike chromosomes, where there's a mechanism for this.) Instead, there's a sort of founder effect every time a cell division takes place.

The graph below shows the average behavior of the diversity if we started with 100 mitochondria all different. As you can see even given this starting point we expect the diversity to be completely eliminated after about 400 cell divisions.

Message 393 of 467 (785440) 06-05-2016 7:59 AM

Reply to: Message 390 by caffeine 06-04-2016 1:47 PM

In addition to what Dr. A said, the replication of mtDNA is severely down regulated during embryogenesis which reduces the per cell copy number creating a mitochondrial bottleneck.This also serves to restrict the mitochondrial haplotypes that are eventually put into oocytes.

Another thing to keep in mind is that the human mitochondrial genome is only about 17k bases as opposed to nuclear DNA which is about 3 billion bases. If the expected mutation rate for nuclear DNA is about 300 bases per generation, the expected mutation rate for mtDNA would be 0.0017 mutation per generation or 1 mutation every 588 generations. Of course, mtDNA mutation rates are higher than that for nDNA due to the less precise replication machinery and less redundancy in DNA repair mechanisms (some estimates are that the rate is 10x higher).

This study empirically determined the mutation rate to be 3 mutation in 705 mtDNA transmissions:

quote:

---

we sequenced the mtDNA control region in 272 individuals, who were related by a total of 705 mtDNA transmission events, from 26 large Icelandic pedigrees. Three base substitutions were observed, and the mutation rate across the two hypervariable regions was estimated to be 3/705 = .0043 per generation (95% confidence interval [CI] .00088�.013), or .32/site/1 million years (95% CI .065�.97).

---

The Mutation Rate in the Human mtDNA Control Region

So we would expect that most of the time the offspring would inherit the exact same mtDNA as the parent had.

HBD

Message 396 of 467 (785457) 06-05-2016 1:04 PM

Reply to: Message 393 by herebedragons 06-05-2016 7:59 AM

Means? When the mtDNA is reproducing it is restricted. Like only a very small number of mitrochondria contibute to the final embryo? I don't get "down regulated" in here though.

Now to put this in the context of this discussion (which I haven't been working hard enough on). This means that the "slate is wiped clean" or almost so regularly. Thus changes we see have to be due to new mutations?

Message 397 of 467 (785483) 06-05-2016 9:55 PM

Reply to: Message 396 by NosyNed 06-05-2016 1:04 PM

Oh, no problem Ned. I'll admit I can use "jargon" at times, the reason is that it is not "jargon" to me. To me the meaning of "down regulated" is just as obvious as "mutation" and neither term seems like "jargon" to me. So it can sometimes be difficult to know when a commonly used genetic term needs more explanation.

When I read some of the physics threads, especially stuff on quantum physics and string theory, it is completely meaningless to me, gooblygook is the correct term I believe. But then again, I don't claim to have any knowledge about the subject matter nor am I especially inclined to try and understand the physics "jargon."

ABE:

I was going to respond in a different thread, but decided it was easier to just do it here. If the conversation needs to continue, we can move it then.

The ovum, or egg, has a large number of mitochondria. But during embryogenesis, the replication of mitochondria is down regulated, meaning simply that they replicate very slowly rather than at a normal pace. As the blastocyst forms, the mitochondria are partitioned into the dividing cells. Because they are not replicating, the number of mitochondria in each cell is greatly reduced compared to the original ovum. Normally, the mitochondria would be replicating so that the number of mitochondria in each cell would remain constant (of course different cell types have differing numbers of mitochondria - some have higher energy requirements than others).

The mitochondria don't begin replicating at a normal rate until I think gastrulation, when cells begin differentiating into different tissue types. By this time, the cell line that will develop into new oocytes will have a limited number of mitochondrial haplotypes. So even if there many haplotypes in the original egg, they have now been segregated into many cell lines and there will very few haplotypes (possibly only 1) that are passed on to the next generation.

I'm not sure "wiped clean" would be accurate, instead just a relatively small number of mitochondria are funneled to new oocytes and so the number of different haplotypes being passed on to the next generation is limited. Also the mutations that will accumulate in the mitochondria that will be passed on to the next generation are only those that occur in the cell line leading to the reproductive cells. So we don't expect large numbers of mutations in each generation nor do expect to see significant numbers of haplotypes being passed on. More like it is a very reliable method of inheritance.

HBD

Edited by herebedragons, : No reason given.

Message 398 of 467 (785550) 06-06-2016 9:01 PM

Reply to: Message 397 by herebedragons 06-05-2016 9:55 PM

Let's say that an ovum has 30 mitochondria. As it starts to develop for the first while they don't multiply. So let's say that they end up with 10 cells lines before the normal multiplication starts. Each of these has 3 mitochondria.

That sort of makes 10 bottlenecked subpopulations out of them One of these goes into the germ line with many fewer mutations than the female parent appeared to pass on.

Message 403 of 467 (786715) 06-25-2016 1:58 PM

Reply to: Message 402 by Emotive 06-25-2016 1:23 PM

I just sent you a test PM.

Message 404 of 467 (786716) 06-25-2016 2:00 PM

Reply to: Message 402 by Emotive 06-25-2016 1:23 PM

Enjoy