Mitochondrial Dna in evolution and disease

[Angela]

See:
http://www.nature.com/nature/journal...ture18902.html

Unfortunately, it's in mice. Now they need to do it for humans.

"Human mitochondrial DNA (mtDNA) shows extensive within-population sequence variability¹. Many studies suggest that mtDNA variants may be associated with ageing or diseases^{2, 3,4}, although mechanistic evidence at the molecular level is lacking^{5, 6}. Mitochondrial replacement has the potential to prevent transmission of disease-causing oocyte mtDNA. However, extension of this technology requires a comprehensive understanding of the physiological relevance of mtDNA sequence variability and its match with the nuclear-encoded mitochondrial genes. Studies in conplastic animals^{7, 8,9} allow comparison of individuals with the same nuclear genome but different mtDNA variants, and have provided both supporting and refuting evidence that mtDNA variation influences organismal physiology. However, most of these studies did not confirm the conplastic status, focused on younger animals, and did not investigate the full range of physiological and phenotypic variability likely to be influenced by mitochondria. Here we systematically characterized conplastic mice throughout their lifespan using transcriptomic, proteomic, metabolomic, biochemical, physiological and phenotyping studies. We show that mtDNA haplotype profoundly influences mitochondrial proteostasis and reactive oxygen species generation, insulin signalling, obesity, and ageing parameters including telomere shortening and mitochondrial dysfunction, resulting in profound differences in health longevity between conplastic strains."

[Maciamo]

We show that mtDNA haplotype profoundly influences mitochondrial proteostasis and reactive oxygen species generation, insulin signalling, obesity, and ageing parameters including telomere shortening and mitochondrial dysfunction, resulting in profound differences in health longevity between conplastic strains."

That's amazing. I suspected that differences in mtDNA haplotypes/haplogroups could lead to variations in fitness, health and longevity, but it looks like the mt-haplogroup you carry could make a whole world of difference to the person you are. MtDNA only represents 0,000005% of the human genome, but each of our cells contains thousands of mitochondria providing practically all our energy. Without them we are like a car without an engine.

Some studies have already showed that some specific mtDNA variations are associated with elite athletic status. For example, among athletes haplogroups J, K and U are associated with sprinters (burning a lot of energy in a short time), while haplogroups H, V and I are linked with endurance.

They mention phenotypic variability. I really wonder if a pair of identical twins were conceived by IVF and one had their mtDNA altered to a completely different mt-haplogroup through genetic engineering, whether they would still grow to look identical or if they would look more different than regular identical twins? They could try in mice, but we are as sensitive in fine phenotypic differences in other species than our own and may not notice it. The difference may not be so much facial features as much as emotional expression reflecting a different way of processing energy. One of them may become weary and irritable more easily than the other. One may be predisposed to be naturally more cheerful or energetic than the other. It would be odd if that wasn't the case.

I have analysed the behaviour and mood of my known relatives sharing my mtDNA (K) and I noticed that we tend to have spikes of energy and cheerfulness, can concentrate hard when properly motivated, but get more quickly tired and irritable than the average population. I also have a remarkably fast metabolism. I can eat as much as I want without gaining any weight. That is in agreement with the sprinter type.

I have noticed that the mtDNA T2 and X2 people I know had, on the contrary, surprisingly even mood and stable energy levels, and it took a lot to make them irritable or lose their temper. On the other hand they don't seem to be able to work as quickly and intensely as me. My T2 relatives have an especially relaxed and laid back nature, but gain weight more easily too.

Feel free to share your own observations.

[Angela]

That's amazing. I suspected that differences in mtDNA haplotypes/haplogroups could lead to variations in fitness, health and longevity, but it looks like the mt-haplogroup you carry could make a whole world of difference to the person you are. MtDNA only represents 0,000005% of the human genome, but each of our cells contains thousands of mitochondria providing practically all our energy. Without them we are like a car without an engine.

Some studies have already showed that some specific mtDNA variations are associated with elite athletic status. For example, among athletes haplogroups J, K and U are associated with sprinters (burning a lot of energy in a short time), while haplogroups H, V and I are linked with endurance.

They mention phenotypic variability. I really wonder if a pair of identical twins were conceived by IVF and one had their mtDNA altered to a completely different mt-haplogroup through genetic engineering, whether they would still grow to look identical or if they would look more different than regular identical twins? They could try in mice, but we are as sensitive in fine phenotypic differences in other species than our own and may not notice it. The difference may not be so much facial features as much as emotional expression reflecting a different way of processing energy. One of them may become weary and irritable more easily than the other. One may be predisposed to be naturally more cheerful or energetic than the other. It would be odd if that wasn't the case.

I have analysed the behaviour and mood of my known relatives sharing my mtDNA (K) and I noticed that we tend to have spikes of energy and cheerfulness, can concentrate hard when properly motivated, but get more quickly tired and irritable than the average population. I also have a remarkably fast metabolism. I can eat as much as I want without gaining any weight. That is in agreement with the sprinter type.

I have noticed that the mtDNA T2 and X2 people I know had, on the contrary, surprisingly even mood and stable energy levels, and it took a lot to make them irritable or lose their temper. On the other hand they don't seem to be able to work as quickly and intensely as me. My T2 relatives have an especially relaxed and laid back nature, but gain weight more easily too.

Feel free to share your own observations.

I'm not sure it affects temperament. I'm U2e, and obviously, so was my mother. :)

She had the patience of Job with anyone and anything; I almost never remember her losing her temper. She also could concentrate for hours and was a total perfectionist in everything she did. She did tire easily.

I, on the other hand, tend to be very impatient, at least with people and their stupidity, and lose my temper quite easily (I had to work very hard at tempering those traits when I became a mother), just like my father, who I doubt was U2e, given how rare it is. Like her, however, I'm a perfectionist, and I can concentrate for hours even on the most mundane tasks.

I never knew anyone less lazy and more hard working than my mother, but she did tire easily, as do I; you just work anyway, nervous energy maybe. We're also definitely both sprinters.

I am developing some of my mother's health issues, however, starting with hypertension, a hypertension that had nothing to do with obesity; when she died in her sixties she was 5'6" tall and barely weighed 120 pounds. In her youth and middle age she didn't even break 110 pounds, and that was without dieting or any of that nonsense. I also got migraines as she did. I just hope I miss some of her other health issues.

My father's family is much healthier. The ones who didn't smoke, the women mainly, lived into their late 80s at least. Even my grandfather on that side, who did smoke, and liked his grappa, was still riding his bicycle up and down the mountain in his eighties.

[Maciamo]

I'm not sure it affects temperament. I'm U2e, and obviously, so was my mother. :)

She had the patience of Job with anyone and anything; I almost never remember her losing her temper. She also could concentrate for hours and was a total perfectionist in everything she did. She did tire easily.

I, on the other hand, tend to be very impatient, at least with people and their stupidity, and lose my temper quite easily (I had to work very hard at tempering those traits when I became a mother), just like my father, who I doubt was U2e, given how rare it is. Like her, however, I'm a perfectionist, and I can concentrate for hours even on the most mundane tasks.

I never knew anyone less lazy and more hard working than my mother, but she did tire easily, as do I; you just work anyway, nervous energy maybe. We're also definitely both sprinters.

I am developing some of my mother's health issues, however, starting with hypertension, a hypertension that had nothing to do with obesity; when she died in her sixties she was 5'6" tall and barely weighed 120 pounds. In her youth and middle age she didn't even break 110 pounds, and that was without dieting or any of that nonsense. I also got migraines as she did. I just hope I miss some of her other health issues.

My father's family is much healthier. The ones who didn't smoke, the women mainly, lived into their late 80s at least. Even my grandfather on that side, who did smoke, and liked his grappa, was still riding his bicycle up and down the mountain in his eighties.

My observations are not based just on one or two people. If I count all my cousins, uncles, aunts, grandmother, grand-aunts, mother's maternal cousins and their children, that's over 20 people who share my mtDNA lineage. I can say that most of them are indeed sprinter types, often hard workers (although that depend on cultural and environmental factors too, including work ethics, ambition, need and motivation), but who get tired and irritable easily.

Tiredness is usually one of the main causes of irritability. If your mother didn't get irritable when she was tired, it may just be that she tried harder to control her emotions or that she had other genes (e.g. higher serotonin levels) that prevented the irritability.

My X2 relatives (8 people) are all surprisingly calm, mild-mannered and kind. That's the kind of people who wouldn't hurt a fly. That really rang a bell when I read on 23andMe's blog in 2009 that 30% of Hutterites, a branch of Anabaptists who immigrated to North America from South Tyrol, belonged to haplogroup X2c1, the very same subclade as in my family. Hutterites are renowned for their dedication to absolute pacifism, a trait of temperament that matches perfectly my X2 relatives. I cannot be certain that the high incidence of X2c1 caused the Hutterites to become pacifists, but it wouldn't surprise me a bit.

[Korbyn]

Well, from my own experiences/opinion: I believe that mitochondria has more to do with the body (biologically) rather than the psyche. (mind) in terms of ability.

I am haplogroup H1; the most common in Europeans; (alongside U5?) and I can remember while in school that I did indeed have a very good endurance when running or exercise. I was one of the best runners and was in prime shape. Even if I skipped school or exercise (because of illness or injury) I would easily rebound and come back just as strong or stronger than my peers. So there may be some truth to that. (haplogroup H and endurance)

People also tell me that they are impressed at how fast I can gain muscle, without much use of things like protein shakes. I also remember in P.E. (in school) since I was a young boy, that I would always be one of the best men at jogging or weight lifting; while all other classmates would stop abruptly in tiredness or agony. (While exercise was painful for me as well; the more I did it, the more it seemed to give me a high and the pain reduced.)

Maybe mitochondria has something to do with pain threshold, oxygen and Endorphins release. I also remember the suggestion of my peers to become a U.S. Marine, but it was not my passion and I was indifferent to this goal; so I guess that means I (not willfully) declined.

[Korbyn]

While I'm on the subject. My family has a history of longevity. Dad's maternal grandmother lived to 92 almost 93. Mom's paternal grandfather lived to 88. Ironically I don't know anything of their mtdna lineages other than they were pretty homogeneous, and shared ancestors.