November 12, 2009

mtDNA haplogroup H and maximal oxygen uptake

Mitochondrion. 2009 Nov 6. [Epub ahead of print]

Human mitochondrial haplogroup H: the highest VO(2max) consumer. Is it a paradox?

Martínez-Redondo D et al.

Mitochondrial background has been demonstrated to influence maximal oxygen uptake (VO(2max), in mL.kg(-1).min(-1)), but this genetic influence can be compensated for by regular exercise. A positive correlation among electron transport chain (ETC) coupling, ATP and reactive oxygen species (ROS) production has been established, and mitochondrial variants have been reported to show differences in their ETC performance. In this study, we examined in detail the VO(2max) differences found among mitochondrial haplogroups. We recruited 81 healthy male Spanish Caucasian individuals and determined their mitochondrial haplogroup. Their VO(2max) was determined using incremental cycling exercise (ICE). VO(2max) was lower in J than in non-J haplogroup individuals (P=0.04). The H haplogroup was responsible for this difference (VO(2max); J vs. H; P=0.008) and this group also had significantly higher mitochondrial oxidative damage (mtOD) than the J haplogroup (P=0.04). In agreement with these results, VO(2max) and mtOD were positively correlated (P=0.01). Given that ROS production is the major contributor to mtOD and consumes four times more oxygen per electron than the ETC, our results strongly suggest that ROS production is responsible for the higher VO(2max) found in the H variant. These findings not only contribute to a better understanding of the mechanisms underneath VO(2max), but also help to explain some reported associations between mitochondrial haplogroups and mtOD with longevity, sperm motility, premature aging and susceptibility to different pathologies.

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6 comments:

Maju said...

It's very difficult to make an assessment from just an abstract (and a poorly written one, btw) but essenially the authors seem to be saying that mtDNA H increases athletic performance and general biotic performance thanks to an apparent (not quantified) improvement in oxygen metabolism, right?

But I wonder: if mtDNA H is so super, why it has not overcome all other haplogroups since it is known to have been around (more than 12,000 years based on fossil data, maybe as much as 40,000 years based on genetic age estimates)? How it is possible that other "competing" haplogroups did not just become extinct in the low population conditions of the Upper Paleolithic?

In fact in Portugal and Morocco mtDNA H does not seem to have increased its total share of the population at all but has remained stable instead.

Also (and always presuming that the conclusions outlined in the abstract are correct) I wonder if the genetic set is correctly determined, i.e. it could be a superset of H (like HV or R0) the one where the relevant mutation happened... or maybe a subset like H1. It would be interesting to determine at molecular level which genes (mutations) are involved in this alleged improvement. Haplogroup H is defined by only two coding region (and no control region) mutations (from HV, only 10 CR mutations from L3), so it should not be that difficult to analyze the implication of these two base changes in a lab.

Annie Mouse said...

"But I wonder: if mtDNA H is so super, why it has not overcome all other haplogroups since it is known to have been around"

Perhaps it has. This would explain the drop in U and the rise in H quite neatly. I have been speculating on a difference of breeding rate also. Between optimized low birthrate hunter gatherers (1 child every 5 years or so) and superbreeders who pop ou at a child every year (only possible after agriculture).

We shall see.

Ken said...

The original hunter gatherers in Europe would have been adapted to the Ice age climate and eating a diet very, very low in carbohydrate.

The switch to agriculture may have significantly disadvantaged most of the European 'low-carb' hunter gatherer mtDNA lines. European mtDNA that is around today may well have been inherited from far less than 5% of the ancestral hunter gatherer women.
Women with mitochondrial haplogroup N9a are protected against metabolic syndrome

It is not terribly surprising that a sample of 20 failed to find a match with later agriculturists.
Populations which were not so adapted to eating meat, ie those on on the southern periphery of the steppe-tundra hunting area, may have been the source of the mtDNA that later became predominant.

Alternatively, Dienkes' Middle Eastern farmers could have supplied the necessary agriculture adapted mtDNA. As the Middle Eastener's non-mitochondrial DNA was not being selected for in the same way it would never have achieved the same displacement of the hunter gatherer's non mitochondrial DNA.

"The occurrence of potentially adaptive mtDNA mutations appears to have been quite a common event throughout human prehistory, because today's haplogroups appear to be separated by many mutations that are adaptive in different contexts."
Say certain mtDNA lines could produce 10% higher fitness in the new situation of high carb diet diet and epidemics of novel infectious diseases brought by incomers. Over many generations the adaptive mtDNA would supplant the others, gradually becoming the norm.

Ancient DNA mutations permitted humans to adapt to colder climates.

The end of the Ice Age would have led to a relatively swift transition to selection against cold adapted mitochdria which may lower fertility in men.

Otzi the Iceman’s mitochondrial DNA

"Close examination of his mitochondrial DNA showed mutations associated with low sperm mobility, so it’s possible he was infertile. The more interesting thing about his mt DNA is that it is a previously unseen variant of K1, and it’s quite possibly extinct in the modern European population."

My conclusion is that being adapted to cold and a diet very low in carohydrate European Ice Age mtDNA became maladaptive after the ice age, especially when agriculture was introduced. It may gradually have been replaced over thousands of years.

Maju said...

Perhaps it has. This would explain the drop in U and the rise in H quite neatly.

But that's only attested in Central Europe, if anywhere. You can't generalize from such a particular case.

Maju said...

Otzi the Iceman’s mitochondrial DNA
"Close examination of his mitochondrial DNA showed mutations associated with low sperm mobility, so it’s possible he was infertile. The more interesting thing about his mt DNA is that it is a previously unseen variant of K1, and it’s quite possibly extinct in the modern European population"
.

First, whether mtDNA causes male infertility is trivial as such because mtDNA is transmitted ONLY via mothers.

Second, K1ö (Ötzi's mtDNA lineage) is 21 CR mutations away from L3, while T2b3a is 24. T2b3a is attested among LBK farmers, what apparently means that Ötzi's lineage existed before that time (my estimates make it Magdalenian, which seems to be related to K1 and T2 expansions, as far as I can see).

Ponto said...

The finding is not significant. The best endurance athletes are not Spanish Caucasian men who are mtDNA H. The best endurance athletes are East Coast Africans, and East Asians whatever their mitochrondrial types.

As for longevity, mtDNA H has never been significantly associated with longevity, neither has mine mtDNA V.

This might floor you, but athletes don't have a proven longevity record. Men generally have VO2Max higher than women do but a statistically lower life expectancy, and any visit to the old folks home will show you that the old gals outnumber the old farts 3:1.

The main reason mtDNA H is the common as muck mtDNA haplogroup among Europeans is that the women possessing were better at dropping female children than the other women of different mtDNA haplogroups.

The actual reasons might be silly like bigger child bearing hips, a more curvaceous, sexy body (the "Venuses" lol), a saucy personality to go with the unseen haplogroup. In the old days, women were a commodity traded by men, their relatives, to sell to other men for trade, diplomacy, alliances, getting rid of surplus women, and so on. In Europeans, the Mesolithics sold their women to the incoming sex starved Neolithic farmers, most of whom were men without families, and who could support having many dependants and children. The Mesolithics couldn't. Their populations had to keep balance with their food supply. Infanticide was practiced by hunter/gatherers to limit populations growth. Old people were routinely left to die as they were burdens. They probably later collected the remains and painted them with ochre but they still those old people out to die. The dominance of male haplogroups of progressive or more warlike people is common everywhere that primitives encounter more technologically progressive humans: in the Americas with the Amerindians, in Australia with the Aborigines, in NZ and Polynesia with the Maori and other Polynesian types.

On the other hand mtDNA H was introduced by the Neolithic farmers, and they just bred like uncontrolled rabbits. Another pair of hands to do grow food, tend the goats, draw water.

Its VO2Max is really irrelevant to the dominance of mtDNA H in western Europe.