That's very interesting. One of the things that's puzzled me about mtDNA is that it's so consistent within the cell. If you think of things from a mitochondrion's perspective it lives in a perpetual cytoplasmic environment, multiplying and occasionally mutating. Why should a typical cell line not come to contain examples of a number of those mutant strains? The mechanism that favours particular mitochondrial lines helps answer this.
Fatal genetic conditions could return in some 'three-parent' babies
Troubling new findings have been discovered that could affect the lives of (misleadingly* branded) "three-parent" offspring born thanks to breakthrough mitochondrial replacement therapy. The technique grabbed the world's attention when in September a baby was born bearing the DNA of three parents, a feat that overcame the …
COMMENTS
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Thursday 5th January 2017 13:57 GMT TitterYeNot
"One of the things that's puzzled me about mtDNA is that it's so consistent within the cell....Why should a typical cell line not come to contain examples of a number of those mutant strains?"
To start with, in sexually reproducing multi-cellular organisms, the vast majority of all those mitochondrial mutations do not get passed on to the next generation of organism. You have your great, great, great, great...............................great, great, great, great grandmother's cell line - the only difference between your mitochondria and hers is a few DNA mutations that have ocurred only in your female ancestors' egg cells (this is why analysis of mitchondrial DNA is such a usefull tool when tracing the historical movement of human populations around the planet.)
Secondly, mitochondria are thought to be bacteria or a similar prokaryote that formed a symbiotic relationship with eukaryotic cells billions of years ago. Free living bacteria benefit from mutation in that it allows them to evolve by natural selection to suit their environment. Mitochondrial mutation is unlikely to benefit the host cell, and probably won't be passed on to the next generation of host organism anyway (see above), so the benefit of mutation is lost (mutation in bacteria is not constant - the rate increases in a stressed i.e. hostile environment, which allows the evolution of better adapted progeny.)
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Thursday 5th January 2017 15:15 GMT Doctor Syntax
"To start with, in sexually reproducing multi-cellular organisms, the vast majority of all those mitochondrial mutations do not get passed on to the next generation of organism."
I know, I'm a biologist by training. But do this thought experiment.
Consider a mitochondrion moving through time. It might be easiest to visualise this as a pipe-line, the length of the pipe being time. As it proceeds the mitochondrion reproduces by fission. Sometimes one of the daughter products has a mutation. Also as it proceeds it passes junctions in the pipe. These are cell divisions. Some of the daughter mitochondria head off down these divisions never to be seen again so what happens to them is irrelevant. But providing you're following the female germplasm line, which is the only one that's relevant, you won't see the successive generations of the host species pass because the cytoplasm just goes on from ovum to ovary to ovum. If you follow that line for long enough some of the mutants will take the same branch at the junctions some of the time. On this simple model you should expect diversity in mitochondrial genomes within individuals.
Yes, the vast majority of mutations never get passed onto the next generations - in much the same way as the vast majority of sperm and pollen never find an ovum with which to fuse, but the critical thing about biology is that the numbers per generation and the numbers of generations are such that vast majority is not the same as totality.
I remember this being raised elsewhere some time ago. It seems that there is some sort of bottle-neck mechanism involved which but I don't recall the details. That means that the ovary to ovum transition might not be as invisible as the above suggests but I'm not sure whether that mechanism is sufficient to guarantee the uniformity found. The fact that the nucleus might be able to exert some selective influence makes a good deal of sense in terms of what's observable in nature. Presumably in evolutionary terms there must be a selective advantage in maintaining consistency of mtDNA.
You're right in implying that things can be different in non-sexual reproduction. In plants chloroplasts are considered to have similar symbiotic origins. Variations there are responsible for some forms of variegation which is why, for instance, the golden holly in my garden needs to be propagated vegetatively.
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Thursday 5th January 2017 21:21 GMT Grikath
"Presumably in evolutionary terms there must be a selective advantage in maintaining consistency of mtDNA."
Given that mtDNA is so far stripped down in the "self-sufficiency" section that any mitochondrion cannot possibly survive unsupported by the body of an eucaryotic cell....
Yes, there's a selective advantage to mtDNA consistency: There's. Hardly. Any. Room. For. Errors. Period. mtDNA mutation frequency is about the same as "normal" DNA. Mutations in mtDNA are, however, almost exclusively lethal to the mitochondrium in question. There's only a couple of spots that can mutate without the mitochondrium conking it, and they lead to very rare, and ultimately lethal diseases...
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Thursday 5th January 2017 23:59 GMT Doctor Syntax
"There's only a couple of spots that can mutate without the mitochondrium conking it, and they lead to very rare, and ultimately lethal diseases..."
You might not have noticed but there are some stretches of mtDNA which are able to show variation. This is what is used in mtDNA typing as sold to genealogists. Although there are differences between different inheritance lines the mitochondria within individuals show a remarkable absence of variation, even in these areas where variation is able to take place.
What the paper being discussed shows is that the eucaryotic host, for want of a better word, seems to exert some control over the multiplication of mitochondria when an artificial process* creates a mixture. This provides at least a partial explanation of how the variation might be reduced.
Such a mechanism is unlikely to exist for the sole purpose of defeating IVF (although Creationists might disagree with that) nor for aiding businesses selling services to genealogists so it's likely that it exists as a result of an evolutionary process.
A functional mutation in a mitochondrion might not necessarily be fatal to the mitochondrion itself - after all, as you pointed out, the mitochondrion is supported by the host cell and, of course, by its fellows. However, if such functional mutants were able to spread they would damage the overall performance of the host organism. Some sort of mechanism for preventing such a spread would provide a selective advantage for the host and the research presented here suggests that genes of the eucaryotic nucleus are indeed involved - just what one would expect from a selective advantage on the host.
The bulk of the Nature paper is paywalled but the more general summary here, http://www.npr.org/sections/health-shots/2017/01/01/507244429/unexpected-risks-found-in-editing-genes-to-prevent-inherited-disorders also linked in the parent El Reg article, would be worth a read. The rates of mitochondrial mutation mentioned there might surprise you.
*Used to attempt to overcome the very mitochondrial genetic diseases you mentioned.
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Thursday 5th January 2017 11:53 GMT Dave 15
why
One thing that puzzles me is why
Same question for all the invitro and other meddling. Sure it I do understand that not producing your own offspring is upsetting for people BUT we have far too many people in the world and many many accounts of perfectly lovely healthy children left rotting unloved, uncared for, lonely, in what amount to cages in 'orphanages' in places like Romania. If you want a kid go and get one of those that already exist but need a parent.
FFKS billions spent on these 'treatments' and 'research' and these other kids are dying in cages in a dirty wet corner
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Thursday 5th January 2017 12:35 GMT Anonymous Coward
Re: why
Adopting a child from an orphanage is a major undertaking - and people tend to want a newborn baby. Adopting older children involves considerably more adjustment on both sides - notwithstanding any inherent health/emotional problems that the process didn't highlight.
IVF research prevents children being born with inherited conditions that would severely limit their quality of life or prove fatal in childhood. Post-natal care for unexpected conditions is a drain on health resources. There are always spin-offs from such research that benefit other areas of health - possibly more than the original field.
It puzzles me why some governments/religions prohibit people from using reliable methods to control their fertility. They even encourage them to have more than the replacement number of children - and often also prevent people being properly educated about sex in the first place.
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Thursday 5th January 2017 14:33 GMT jonathan1
Re: why
I don't disagree with you sentiment about children that could do with help but parenting is a complex issue both biologically,emotionally and socially. Its not case of simple substitution of the biological withe adopted.
I think its a sign of progress that we are able to do this. In the same way that any medical advance can improves the life of an individual. Just before Christmas, a statement was made in the news that there are more women now with narrower pelvises having children; which means natural birth is more difficult/unlikely. It was even followed up with most women in this category would die in childbirth. Whilst these things maybe true...I'd rather not have folks die if we have the means to save them.
I do disagree with the notion we have "far too many people in the world". I haven't seen any evidence for that. I mean how many is too few or too many? The only fact we can see is that we have more people alive than we have in the past and its possible to make the hypothesis that populations aren't distributed in the most effective and efficient manner uniformly across the world. I.e. high population density in some areas causing a strain on available resources or low density in other areas the same albeit in a different manner.
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Thursday 5th January 2017 22:13 GMT Anonymous Coward
Re: why
"I think its a sign of progress that we are able to do this"
Many male animals will deliberately kill the mate's existing offspring by another male. In the Ottoman Empire succession for the Caliph - the winner usually had all the male family rivals killed immediately to avoid future civil wars.
On the other hand - many social animal groups will foster orphans or even succour any youngster that happens to be in need.
The latin word "alumnus" - usually seen nowadays as the plural "alumni" - originally had the meaning of "nurtured". In Ancient Rome it covered the practice of helping to raise, and possibly later on adopting, someone else's child. Not necessarily because the child was an orphan or the person needed an heir. Nowadays the word "mentor" or "protégé" might be used to signify a similar beneficial relationship.
The Ancient Greeks/Romans sometimes left unwanted newborns at known places - either to die of exposure or to be taken in by someone else.
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Thursday 5th January 2017 12:38 GMT John H Woods
Re: Prediction...
"Got anything to back that up ?"
I'll back that up. Whilst I understand why the scientists are keen to emphasise that mtDNA does not confer any identity linked traits (to mitigate against people wibbling on about designer babies), we have always found that there is always more to find (e.g. epigenetics vs pure sequencing) and our genetic (and, perhaps more significantly, biochemical) knowledge is clearly some way from being complete, even assuming complete knowledge is possible.
As it is trivially true that mtDNA mutations can cause different phenotypes (otherwise we wouldn't even be discussing this) it is almost certain that other mutations, or other epigenetic factors, would result in physical manifestations of those differences.
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Thursday 5th January 2017 12:46 GMT Anonymous Coward
Re: Prediction...
"Got anything to back that up ?"
Given that the understanding of DNA is still in its infancy - it is reasonable not to make definitive statements at this stage.
A recent article in Quanta Magazine revealed that the different ways that DNA can coil upon itself can alter the way identical genes are expressed.
https://www.quantamagazine.org/20160105-supercoiled-dna/
There is an old saying "If an expert says something can be done - then it undoubtedly can be done. If an expert says something can't be done - then they are possibly going to be proved wrong in the future."
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Thursday 5th January 2017 13:10 GMT Brewster's Angle Grinder
Re: Prediction...
"Got anything to back that up ?"
To add to what John says: genes turn on and off in response to environmental cues; mitochondria have a large influence on the immediate environment. There's work on animal models (fruit flies and cephalopods ) mentioned in one of the linked articles, and talk about mitochondria forming a co-evolved system with nuclear DNA. I'm slightly sceptical about the latter, though; sexual reproduction introduces genes from the father that didn't evolve in step the the mitochondria.
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Thursday 5th January 2017 17:41 GMT JeffyPoooh
Re: Prediction...
AC stormed "Got anything to back that up ?"
It's clearly marked "Prediction".
The subtle clue is that mtDNA does have significant effects, such as serious diseases. They'll *probably* eventually figure out that there's some clearly identifiable trait resulting from mtDNA. But it's just a *prediction*.
And to your 2nd point: yes, I have independently worked out an interesting mathematical effect of mtDNA inheritance which many scientists appear to have overlooked. It may take them another (!) ten years to realize and 'hoist aboard' my observation. No rush.
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Saturday 7th January 2017 19:02 GMT Anonymous Coward
Re: Prediction...
"It's clearly marked "Prediction"."
Then they're confident it WILL happen. It's in the word "predict": combining "pre" and "edict", saying something MUST happen (an edict is equivalent to an order or demand) before (pre) it even happens.
Now if they were to say "Hypothesis", then it's safe to say they're not fully confident and that it only COULD happen.
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Thursday 5th January 2017 13:01 GMT phil dude
Re: Prediction...
There are a number of genes from the mitochondria co-expressed within the nuclear genome.
Every picosecond of your existence, is dependent upon the mitochondrion electronic transport chain.
If your mitochondria doesn't work well, identity linked traits are the *least* of your problems.
Biology was not engineered, it evolved, making the search for knowledge of the functionality *complex*
We are still trying to account for all the bits needed that sum up to make up *you*, and that includes the mitochondria.
P.
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Thursday 5th January 2017 16:01 GMT Tony Haines
Re: Prediction...
Guys, I wouldn't worry too much about what the scientists know.
By the time you've lossily compressed and reprocessed the information inherent in a piece of complex science into a news article, most of the clauses and qualifications have been stripped away.
Or more succinctly:
"All sound bites are wrong."
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Thursday 5th January 2017 13:35 GMT chewyfruitloop
suck it darwin
so, we've figured a way to beat natural selection... because thats going to end well...
I know theres a fairly powerful in built desire for your own progeny...but if you have a fatal genetic issue, then would have taken that as a signal that you shouldn't be having kids
...this may be an unpopular opinion, but having first hand experience of seeing what inherited genetic issues do... perhaps a thought should have been given for the consequences to the child should the DNA blending not work as predicted
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Thursday 5th January 2017 14:15 GMT John H Woods
Re: suck it darwin
"so, we've figured a way to beat natural selection ... if you have a fatal genetic issue, then would have taken that as a signal ..." -- chewyfruitloop
Natural selection cannot be beaten: in this case the "fatal genetic issue" is no longer fatal thanks to a change in the environment (the availability of technological remediation). Genes don't send signals --- they impact the reproducibility of the genome they are part of or, if they don't, they drift randomly through the population over time.
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Thursday 5th January 2017 14:38 GMT Dr. Mouse
Re: suck it darwin
so, we've figured a way to beat natural selection... because thats going to end well...
If this is your viewpoint, we have been "defeating natural selection" for thousands of years.
Natural selection/evolution involves mutations which make us better suited to our environment. Conversely, for a hell of a long time, humans have been adapting our environment to suit us. Similarly, we have discovered medicines which stop disease from killing off the weak.
If you want us to get back to your definition of natural selection, we would need to abandon all technological, medical and industrial advancements we have made, and go back to being hunter-gatherers living in caves. Oh, and not wear clothes: Our bodies will evolve fur if we need it.
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Thursday 5th January 2017 16:08 GMT Daggerchild
Re: suck it darwin
and behold, Trump voters.. attacking Obamacare..so, we've figured a way to beat natural selection... because thats going to end well...
If this is your viewpoint, we have been "defeating natural selection" for thousands of years.But as to the posters point that such meddling is 'unnatural', that is to entirely misunderstand the rules of the Game of Life. We are to 'survive', to 'improve', by *any* means we discover. Nothing is off limits.
The vast majority of life cheats by ripping apart and stealing the work done by co-contestants anyway. Mitochondrial transplants improve the chance of survival by removing a blown component and inserting a genuine and naturally sourced replacement. That amount of meddling is nothing compared to the biomass of organisms that were terminated or had their evolution deliberately deformed to make your burger.
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Thursday 5th January 2017 15:46 GMT inmypjs
Re: suck it darwin
"so, we've figured a way to beat natural selection.."
I was going to post "and Darwin continues to spin".
Natural selection continues but for humans the criteria have drastically changed in the last 100 years or so. Survival of the fittest which has worked for millions of years is being replaced by survival of the dim and bad at contraception. Maybe in a couple of thousand years we will run out of smart people to look after the dim ones and the criteria will revert.
I sometimes wonder what the world would be like if Hitler had won, would we all be 6'6", blonde, and jolly smart?
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Thursday 5th January 2017 21:35 GMT Anonymous Coward
Re: suck it darwin
"I sometimes wonder what the world would be like if Hitler had won, would we all be 6'6", blonde, and jolly smart?"
Looking at pictures of their leaders and the rank and file - it would appear that the supposed physical Aryan super-type was not predominant in the German/Austrian population. It is probable that creating a population that is "jolly smart" would soon lead to a revolution from the inside against a totalitarian style of government.
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Thursday 5th January 2017 16:16 GMT inmypjs
Re: suck it darwin
"we're able to repair defective genes will be the successful evolutionary strategy."
The genes benefiting from the technology are not the ones responsible for creating it, they end up competing. It is more a suicidal than successful evolutionary strategy for the genes that came up with the technology.
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Thursday 5th January 2017 16:26 GMT BinkyTheMagicPaperclip
Re: suck it darwin
Where do you draw the line? I don't necessarily disagree, particularly as I don't want children, but the amount of money and time spent on assisting conception is not even vaguely logical.
If funding to improve conception for couples with inherited conditions is stopped, why is funding available in the first place for those with non viable fertility levels? It's hardly as if the world is short of babies.
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Thursday 5th January 2017 21:45 GMT Anonymous Coward
"If funding to improve conception for couples with inherited conditions is stopped, [...]"
...then the burden on the health system for post-natal care of those born with the conditions will increase.
Friends had a child with a totally unsuspected inherited genetic condition that usually resulted in death by their teens. Modern medical advances have now extended a productive life expectancy to the 50s - albeit with significant ongoing financial costs to the health service for emergencies and medication. The child, now an adult, has advised their siblings to have an abortion if they find they have conceived a foetus with that condition.
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Tuesday 17th January 2017 04:15 GMT Jim84
Allotopic expression
Moving the 13 protein coding mtDNA genes to the nucleus is another possible approach rather than mitochondrial donation from another woman's egg.
http://www.sens.org/research/intramural/mitochondrial-mutations
https://www.ncbi.nlm.nih.gov/pubmed/27596602
Only problem with that approach is the children would probably have longer healthier lives than their peers, given the large amount of circumstantial evidence of the involvement of damage to the mitochondrial genome in aging.