Mitochondria in Sperm Defects?

[Endy0816]

Anyone know if these are more likely to carry defects than those from the egg?

 

I've been trying to reason out why there is a selective bias against them. Only idea I've been able to come up with, besides sheer dumb luck and an overzealous protection system for the egg.

[Robittybob1]

Anyone know if these are more likely to carry defects than those from the egg?

 

I've been trying to reason out why there is a selective bias against them. Only idea I've been able to come up with, besides sheer dumb luck and an overzealous protection system for the egg.

Mitochrodrial DNA is always from the egg, the mother's side, maternal mitochondrial DNA. http://en.wikipedia.org/wiki/Mitochondrial_DNA

 

In humans, mitochondrial DNA can be assessed as the smallest chromosome coding for 37 genes and containing approximately 16,600 base pairs. Human mitochondrial DNA was the first significant part of the human genome to be sequenced. In most species, including humans, mtDNA is inherited solely from the mother.[3]

[Endy0816]

That isn't always true.

 

http://www.nejm.org/doi/pdf/10.1056/NEJMoa020350

 

A man was found to have inherited some of his mitochondria from his father.

 

I'm just trying to figure out why the mitochondria don't attempt to ensure they are passed along more often.

[Robittybob1]

That isn't always true.

 

http://www.nejm.org/doi/pdf/10.1056/NEJMoa020350

 

A man was found to have inherited some of his mitochondria from his father.

 

I'm just trying to figure out why the mitochondria don't attempt to ensure they are passed along more often.

Well that was interesting. Thanks

[Endy0816]

Welcome

 

The whole UK decision on mDNA replacement therapy was what got me thinking about this.

 

http://news.sciencemag.org/biology/2015/02/u-k-parliament-approves-controversial-three-parent-mitochondrial-gene-therapy

[MonDie]

I'm just trying to figure out why the mitochondria don't attempt to ensure they are passed along more often.

 

Not that I'm some kind of expert. It's just logic...

 

It would seem that

 

either maternal mitochondria are in an advantageous position, which may have been selected for if paternal inheritance is detrimental to the organism, since lack of genetic recomination puts the mitochondrium at a huge disadvantage to the nucleus,

 

or no adaption was required because paternal inheritance is detrimental to the organism to such a degree that it outweighs the benefit to the mitochondria anyway, since the mitochdrium's fitness is affected by the organism's fitness.

Edited March 23, 2015 by MonDie

[Robittybob1]

Welcome

 

The whole UK decision on mDNA replacement therapy was what got me thinking about this.

 

http://news.sciencemag.org/biology/2015/02/u-k-parliament-approves-controversial-three-parent-mitochondrial-gene-therapy

So what is your view point?

[StringJunky]

It's probably just a simple numbers game of one statistically overwhelming the other. In an egg there are 100 000 - 500 000 mitochondria vs 700 - 1200 in sperm. They are there but it's a needle-in-a-haystack job finding them.

Edited March 23, 2015 by StringJunky

[Robittybob1]

It's probably just a simple numbers game of one statistically overwhelming the other. In an egg there are 100 000 - 500 000 mitochondria vs 700 - 1200 in sperm. They are there but it's a needle-in-a-haystack job finding them.

But it seemed to say that this proportion does not continue as the embryo develops, the male sourced mtDNA fades out, except in rare cases it seems.

There must have been a reason the body evolved a method of just having the one type of mitochondria.

So in this new technology, where they swap mitochondria, are they having to replace all 100,000 or so of mitochondria in the egg?

[Endy0816]

Not that I'm some kind of expert. It's just logic...

 

It would seem that

 

either maternal mitochondria are in an advantageous position, which may have been selected for if paternal inheritance is detrimental to the organism, since lack of genetic recomination puts the mitochondrium at a huge disadvantage to the nucleus,

 

or no adaption was required because paternal inheritance is detrimental to the organism to such a degree that it outweighs the benefit to the mitochondria anyway, since the mitochdrium's fitness is affected by the organism's fitness.

 

 

It's probably just a simple numbers game of one statistically overwhelming the other. In an egg there are 100 000 - 500 000 mitochondria vs 700 - 1200 in sperm. They are there but it's a needle-in-a-haystack job finding them.

 

They are passed along more commonly in other species though. Sheep for instance.

 

In contrast for fruit flies paternal mitochondria are actively segregated and eventually secreted.

 

So what is your view point?

 

I'm fine with it. Basically swapping the egg the nuclear DNA finds itself in(ie. they aren't really moving mitochondria around).

 

I was thinking though at the cost of a donor egg and moving around DNA, it'd be smarter to utilize paternal mitochondria. Only natural known case turned out badly though for the individual. I suppose we could just screen candidate mitochondria but still leaves one wondering.

Edited March 23, 2015 by Endy0816

[StringJunky]

But it seemed to say that this proportion does not continue as the embryo develops, the male sourced mtDNA fades out, except in rare cases it seems.

There must have been a reason the body evolved a method of just having the one type of mitochondria.

So in this new technology, where they swap mitochondria, are they having to replace all 100,000 or so of mitochondria in the egg?

No, they take the gamete out and put it in another donated oocyte that has had its gamete taken out. mtDNA then is from the egg donor.

 

Edit; Xposted with Endy

 

 

 

This Wiki is quite interesting.

Edited March 23, 2015 by StringJunky

[MonDie]

I tried.

[Endy0816]

Yeah, I don't know either just trying to figure out some of the why of it all.

[Robittybob1]

No, they take the gamete out and put it in another donated oocyte that has had its gamete taken out. mtDNA then is from the egg donor.

 

Edit; Xposted with Endy

 

 

 

This Wiki is quite interesting.

Yes that sounds easier. Why did I think they were transferring mitochondria? Thanks to both of you for clearing that up.

[StringJunky]

Yeah, I don't know either just trying to figure out some of the why of it all.

This snippet seems to support - as one of the possibilities - what I was saying about sheer numbers being the determinant; they are there but very rare. The whole article is worth reading. it's one of the references in the Wiki article I linked earlier.

 

 

The results of Kraytsberg et al (2004) show that recombination has been fairly frequent in the individual they study. Even if we assume that all identical sequences are the product of the same recombination event, there must still have been 16 events. Unfortunately, this observation does not give us a handle on how frequent recombination is likely to be in the population, since this depends on the rate of paternal leakage; yet, we have no precise estimate of this parameter. At most, one presumes it must be less than 1 in 1000, since there are 100 000 mitochondria in the human egg and only 100 in the sperm (Satoh and Kuroiwa, 1991).

 

http://www.nature.com/hdy/journal/v93/n4/full/6800572a.html

Edited March 23, 2015 by StringJunky

[MonDie]

This snippet seems to support - as one of the possibilities - what I was saying about sheer numbers being the determinant; they are there but very rare. The whole article is worth reading. it's one of the references in the Wiki article I linked earlier.

 

That would be the proximate cause. The OP proposed an ultimate cause, namely, that sperm mtDNA has more mutations. Admittedly, your proximate cause wouldn't be a clear example of adaption.

 

Nice Nature abstract!

Edited March 24, 2015 by MonDie

[CharonY]

There are two basic hypotheses regarding maternal inheritance of mitochondria. Note that selection is not a necessary factor here. In the dilution hypothesis as outlined above it is a sheer numbers game. It is quite possible that this is merely down to the fact that sperm cannot or need not contain as many mitochondria as oocytes.

 

However, in some animal models evidence for a second, mechanism, the active degradation of paternal mitochondria have been gathered. Different mechanisms have been identified ranging from mammals to slime mold.

 

In biology the why question is quite dangerous. It is always attractive to speculate some evolutionary mechanisms somewhere, but often it is incredibly hard to find specific evidence. It then becomes too easy to build up narratives that make intuitive sense, but are not supported but actual data. For instance, it makes sense to speculate that during the swimming stage higher oxidative stress causes DNA damage. But then it does not explain why uniparental inheritance exist in isagamous organisms such as Physarum.

 

Or one could speculate some competition between mitochondria, where the inequal distribution of gamete size and composition leads to the the maternal one winning out. But again, without further data they will remain speculative narratives.

[MonDie]

Or one could speculate some competition between mitochondria, where the inequal distribution of gamete size and composition leads to the the maternal one winning out. But again, without further data they will remain speculative narratives.

 

Not quite maternal and paternal mitochondria, but rather a biparental strain and uniparental strains.

Edited March 24, 2015 by MonDie

[Endy0816]

My thoughts on the numerical hypothesis are that the ratio could be altered afterwards and if a numerical advantage is all that is needed then these active systems make little sense. Maternal mitochondria shouldn't have any reason to want to be in every offspring's cell, just the cells that go on to make the next egg.

 

It's like they are saying a 1000:1 advantage is not enough and that they need to call in an airstrike.

 

and yeah, I know the risks of asking 'why' in Science. We're the ones looking to fix the resultant issue of(virtually) perpetual inheritance of malfunctioning mitochondria though. On the surface you'd think 50/50 odds would make more sense.

 

I was hoping someone somewhere had simply ran an analysis on a bunch of their genomes. That would be pretty conclusive one way or another. Looking at the numbers involved though seems like that may have been an unrealistic hope. Think I'll take a look at the variants out there that lack genetic material. If inheritance patterns vary that could provide some insight.

[CharonY]

My thoughts on the numerical hypothesis are that the ratio could be altered afterwards and if a numerical advantage is all that is needed then these active systems make little sense. Maternal mitochondria shouldn't have any reason to want to be in every offspring's cell, just the cells that go on to make the next egg.

 

It's like they are saying a 1000:1 advantage is not enough and that they need to call in an airstrike.

 

and yeah, I know the risks of asking 'why' in Science. We're the ones looking to fix the resultant issue of(virtually) perpetual inheritance of malfunctioning mitochondria though. On the surface you'd think 50/50 odds would make more sense.

 

I was hoping someone somewhere had simply ran an analysis on a bunch of their genomes. That would be pretty conclusive one way or another. Looking at the numbers involved though seems like that may have been an unrealistic hope. Think I'll take a look at the variants out there that lack genetic material. If inheritance patterns vary that could provide some insight.

 

I am not sure how genome comparison would yield specific insights as outlined in OP. Or maybe I am missing something here. I am also not sure about the reasoning in the first part, you mean why the degradation pathways exist? The latter is a rather new finding that put the dilution hypothesis (that has been around for quite a while) in question.

 

 

Not quite maternal and paternal mitochondria, but rather a biparental strain and uniparental strains.

 

I do not understand what that means.

[Endy0816]

 

I am not sure how genome comparison would yield specific insights as outlined in OP. Or maybe I am missing something here. I am also not sure about the reasoning in the first part, you mean why the degradation pathways exist? The latter is a rather new finding that put the dilution hypothesis (that has been around for quite a while) in question.

 

Just the genomes of mitochondria in the Spermatogonium to those in the resulting sperm after allowing some time to pass and exposing them to stresses typical to what they would experience in the natural course of events. Probably easier said than done though.

[CharonY]

Well, it is not terribly tricky, at best slightly on the expensive side. But even if you see higher mutation rate it does not necessarily explain why maternal is favored. As I mentioned, in some organisms, which are isogamous (i.e. the gametes are physiologically similar or the same) also uniparental inheritance can be observed. It could be a contributing factor, or it is just a side effect of some other mechanism. To the best of my knowledge (which is admittedly limited) we simply do not know.

 

In general, mitochondrial mutation rate is rather high and there may be certain selective features in there. In this respect dilution becomes more interesting again, as under stringent conditions (to minimize mixtures of mitochondria, or heteroplasmy) only few are likely to survive.

 

The dilution effect is something that is well known to happen in bacteria with respect to plasmid propagation, and I suspect a similar logic.

 

There are estimates somewhere that put sperm mtDNA at a higher mutation rate, though this could be muddied by the high proliferation rate. But again, this alone does not seem to explain why homoplasmy is preferred.

As a counterpoint it is as likely that it is due to the presence of the molecular apparatus (maybe linked to sexual reproduction in general) that maintains it. An interesting link is that in mouse either homoplasmic (paternal or maternal) were apparently normal, but heteroplasmic ones were not (Sharpley et al. Cell 2012). So one could speculate that the cell needs to maintain homoplasmy (for some reasons) and since the maternal cell carries most of the proteins, the apparatus may favor its own.

Edited March 24, 2015 by CharonY

[Endy0816]

That was an interesting read.

 

http://www.sciencedirect.com/science/article/pii/S0092867412011725

 

I'm liking their logic. Basically limiting incompatibly issues.

[MonDie]

For instance, it makes sense to speculate that during the swimming stage higher oxidative stress causes DNA damage. But then it does not explain why uniparental inheritance exist in isagamous organisms such as Physarum.

 

I had to be refreshed on that! I sort of skimped on the metabolism chapters.

 

Fertilization and elimination of the parental mitochondrial genome. JM Cummins, 2000

Apparently the "reactive oxygen species" which the mitochondria serve to isolate can damage the DNA, although "the common assertion that mitochondria lack mechanisms to repair oxidative damage to DNA appears to be false (Cummins, 2000)"

I initially imagined errors in replication during spermatogenesis, but could sperm mitochondria be more active and thus suffer more oxidative damage?

Apparently this was the topic of the last 3 paragraphs of the sciencedirect link, but it looked like jargon at first glance.

Edited April 7, 2015 by MonDie

[Endy0816]

Saw this earlier, thought it interesting:

 

 

Mitochondria are crucial to cellular processes, providing respiratory and metabolic functions that power a cell. Previous research has shown that nearly all animals inherit mitochondria exclusively from their mothers, while paternal mitochondria are selectively destroyed in fertilized egg cells. The exact mechanisms behind this process, however, have remained unclear.

 

After studying this phenomenon in nematodes (C. elegans), a multicellular roundworm commonly used for genomic studies, CU-Boulder researchers discovered that the worm’s male sperm commit a form of mitochondrial “suicide” shortly after fertilizing a female egg cell.

 

The male sperm mitochondria release an enzyme called endonuclease G that destroys its own mitochondrial DNA. The paternal mitochondria also lose their inner membrane integrity, which marks them for destruction by the egg’s own automatic disposal processes.

 

“The big surprise is that paternal mitochondria actively initiate their own demise very early in the process by releasing this endonuclease into the matrix to degrade the mitochondrial genome,” said Ding Xue, a professor in CU-Boulder’s Department of Molecular, Cellular and Developmental Biology and senior author of the new study.

 

http://www.colorado.edu/news/features/solving-mitochondrial-mystery