Mitochondria and Symbiosis: Just who is running this show?

This post, which ends as usual as an account of another amazing aspect of mitochondria, started life wondering why the possession of Neanderthal genes made those with them more susceptible to Covid19 than those without. It seems clear now that Africans, who do not have Neanderthal DNA, become less seriously ill with Covid19 than most of the world who do. 

Amongst the possessor of these genes South Asians seem to have drawn the shortest straw possessing more Neanderthal genes which have been particularly associated with pathogen vulnerability. Australian aboriginals also have Neanderthal DNA but uniquely they also have DNA from the mysterious Denisovans who co-existed with modern man and neanderthal but left little trace of themselves before becoming extinct. The aboriginal groups in Australia seem to have avoided the worst of Covid19 but not through any evidence of innate immunity and so nothing can be said about the Densovan DNA in this context. 

  The Joy of Surfing 

Whilst surfing such topics I came across the most extraordinary revelation ( to me at least). Neanderthal populations according to the fossil records ultimately possessed no neanderthal mitochondrial DNA at all! It was modern human mtDNA, the same as us. 

It looks like an African female (a modern human) seeded the neanderthal population with ‘our’ mitochondria about 200,000 or so yrs ago. Via her offspring, over the following millenia that seed population of mitochondria wiped out neanderthal mtDNA even though her original seed nuclear genes (nDNA) would have been near infinitely diluted through interbreeding amongst the neanderthal populations. Paradoxically then, nearly all humans outside Africa including Australian aborigines possess nuclear neanderthal DNA (nDNA) but no neanderthal mitochondrial DNA (mtDNA). Also, incidentally, the mtDNA from the Denisovan is also lost today despite the appearance of nuclear genes in the aboriginal population. 

Are we looking at a mitochondrial ‘land-grab’, a take-over bid for the endoplasmic-ecology of homo? Is this what mitochondria do? 

The next line of thought was xenobiotic. Human xenomitochondrial cybrids to be precise! Quite simply, how goes trans-species mitochondrial transplants? ‘Topping up’ the quota of human cell mitochondria is a well known experimental technique used to ‘supercharge’ underperforming myocytes after cardiac arrests. It works, for a while and then the population of mitochondria drops to normal levels with no harm done. 

But how about xeno biology? What is the fate of transplanted chimpanzee or gorilla mitochondria? Such transplants work too. Well in vitro they does, but there is some ‘push-back’ from the host as there are deficiencies in various enzyme complexes in the respiratory chain. The interplay between the host nDNA and mtDNA is complex and unpredictable. 

In the lucrative world of animal cloning ( horses, cows, sheep) xenobiology is deeply investigated. To cut a long story short it is easy enough to introduce (say) bovine mitochondria into sheep oocytes (eggs) which can readily proceed to the blastocyst but invariably the cybrid cell fails to implant in the host and develop normally. Similar findings have been found with mice oocytes acting as host to bovine mitochondria.

Mitochondria in mammals are inherited only through the female line via her eggs ( oocytes) so it is relatively easy to inject mtDNA, mitochondria or cytoplasm containing mitochondria into them and produce cybrids but by and large it is not successful from an intra-species perspective. It seems mitochondrial and nuclear DNAs are too subtly integrated to allow a crude transplant even within mammals. This is a shame as I always wanted to read about bat-human cybrids on account of the superb performance of the former’s mitochondria. 

In the homo story above though no alien mitochondria are introduced into an egg. 

The ‘mother’s’ mitochondria receive no challenge from the sperm of the male which carry no mitochondria and so no mtDNA. However, to replace over time the indigenous population’s mtDNA as in the case of the neanderthals it must follow that reproductive success ( from embryo implant to full term to survival) must have been enhanced for the neanderthal by the presence of modern human mitochondria. The story of the neanderthal mtDNA creates a fascinating picture of mitochondria as semi-autonomous populations able to move between creatures that can successfully interbreed. 

It is already well known that mitochondria which are reproducing can be selected for within a cell by energetic demands or even through senescence in terms of numbers, size, ROS production and efficiency. Now it seems, they have a bigger Darwinian ‘landscape’ to operate within, limited only by the species barrier. In this case mitochondrial populations will be selected for on the basis of the successful reproduction of their hosts. 

 The question that is begged is: does this mean morphologically quite different creatures which eventually end up using the same power-plant will converge phenotypically? Or will, like cars with identical engines see one succeed and the others fail. In other words are mitochondria limiting species differentiation? 

Just who is running this show?