lett

There is a possibility that a mitochondrion could eliminate those mutations that distort the double-stranded mtDNA, because such mutations can be physically detected by a set of enzymes.

Having detected the distortion the enzymes could simply destroy the entire copy of the genome containing the mutation.

The destroyed copy could be replaced, sooner or later, by the replication of an unmutated copy of the mtDNA in the same mitochondrion. This is possible because each mitochondrion contains several copies of its mtDNA. Indeed, I suggest that this is the reason why a mitochondrion contains several copies of its genome.

Andrew Gyles

This letter was not published in 'Nature'.

Published on this site 16 August 2000. © Andrew Gyles

________________________________CONTENTS

On 30 July 2000 I sent the following letter to a scientist who studied mitochondria:

Possibility that mitochondria can eliminate some mtDNA mutations

There is a theoretical possibility that a mitochondrion can eliminate those mutations that cause a distortion of the double-stranded mtDNA, because such mutations can be physically detected by a set of enzymes.

All the enzymes then have to do is to destroy the entire copy of the genome containing the distorted mtDNA.

The destroyed copy of the mitochondrial genome can be replaced, sooner or later, by the replication of an unmutated copy in the same mitochondrion.

It is interesting to note that enzymes in the nucleus try to do the same thing. But of course, having detected a chromosome distorted by a mutation they cannot destroy the chromosome. If they did that they would not have an unmutated copy to replicate and so make good the loss. The homologous chromosome is not an identical copy. So the best they can do is to 're-pair' the distorted part of the double-stranded nuclear DNA. This is a chancey business because they cannot 'know' which base or bases to leave in and which to cut out. But it is better than doing nothing.

It is conceivable that a high mtDNA mutation rate in somatic cells is an indication that this hypothetical system for eliminating mitochondrial mutations that cause distortions in double-stranded DNA has failed in those cells.

I think it is worth noting that if such a system is at work in the mitochondria of female germline cells it might be applied with different vigour in different species of animal. In that case it is possible that the mtDNA mutation rate in humans is much lower than has been assumed in studies of human evolution based on the 'mtDNA sequence divergence rate'. As far as I know this rate has never been objectively measured. One can point to faults in Alan Wilson's calculation of the human divergence rate.

I hope you do not mind my writing to you.

Andrew Gyles

Published on this site 26 August 2000. © Andrew Gyles

________________________________CONTENTS

On 14 July 2000 I sent the following letter to the Editor of the weekly magazine published in London, 'New Scientist':

Mitochondrial DNA in evolution research

Why does each mitochondrion contain several copies of its single chromosome? I suggest it is because of the hostile conditions for DNA inside a mitochondrion. Oxygen free radicals produced by the respiratory chain can damage mitochondrial DNA, causing mutations.

It would be a simple matter for a set of enzymes to detect any mitochondrial chromosome deformed by a mutation because the opposing nucleotide bases no longer fit each other.

The enzymes could then destroy the chromosome. It could be replaced, sooner or later, by the replication of an unmutated copy in the same mitochondrion.

It is worth noting that such a mechanism for eliminating some mitochondrial mutations (those that deform the double-stranded DNA) would make it possible for different species of animal to have different mitochondrial mutation rates.

Andrew Gyles

This letter was not published in 'New Scientist'.

Published on this site 10 August 2000. © Andrew Gyles

________________________________CONTENTS

On 26 June 2000 I sent the following letter to a scientist who studied mitochondria:

Mutations in mitochondria

Dear...

The following is the text of a letter I have sent to the Editor of the journal Science. I think that it has possible implications for the understanding of mitochondrial diseases.

It also has implications for the study of evolution using mtDNA sequences, because it implies that different species could have markedly different mtDNA sequence divergence rates, depending on how vigorously they eliminated their mitochondrial mutations.

Sincerely,

Andrew Gyles

The text of my letter to the Editor of 'Science', 24 June 2000 (below), followed.

Published on this site 10 August 2000. © Andrew Gyles

________________________________CONTENTS

On 24 June 2000 I sent the following letter to the Editor of the weekly journal published in Washington, 'Science':

Mutations in mitochondria

There is a theoretical possibility that mitochondria could eliminate mutations to their chromosome. Each mitochondrion contains several copies of the same chromosome. It could therefore detect any chromosome containing mispaired strands and destroy it, and replace the destroyed chromosome by replicating one of its unmutated copies.

Andrew Gyles

This letter was not published in 'Science'.

Published on this site 10 August 2000. © Andrew Gyles

________________________________CONTENTS

On 19 June 2000 I sent the following letter to a scientist with whom I had previously corresponded:

Proposed lab test of 'Out of Africa'

I have described a proposed laboratory experiment on mitochondrial mutation rates (speeded up using X-rays or some other mutation-causing agent) that would test the central assumption of the 'Out of Africa' hypothesis. My idea is that humans may correct mutations of their mtDNA much more effectively than chimpanzees and other animals do.

If this experiment turned out as I expect it would blow the 'Out of Africa' theory out of the water.

It's at my website in America: www.oocities.org/acgyles .

I'm getting about five 'hits' a day at this site, on rare occasions 10 or 15.

Regards,

Andrew

Published on this site 10 August 2000. © Andrew Gyles

________________________________CONTENTS

Oversights in calculating when mitochondrial Eve lived

On 17 March 2000 I sent a second letter to the Editor of 'Nature', the weekly journal published in London. I introduced it to the editor with a short note, part of which follows:

'I submit a Letter to the Editor headed "Oversights in calculating when mitochondrial Eve lived". The subject has been controversial since Nature published the article by Wilson et al in 1987. Gradually, though, Wilson's model has come to be accepted as the standard one. I have heard that some authors writing up evolutionary studies based on nuclear gene sequences now seek to explain their results in terms of the "standard model" even if they don't obviously support it, because they are afraid that if they contradict the standard model they will not get published. This situation cannot be good for science. I hope you will find room in your Letters page to publish a contrary view that is not based on original research (I am not able to do that) but on an examination of the logic that supports the Modern African Eve model. I believe that that logic is flawed and the conclusions based on it are insecure.

Regards, Andrew Gyles'. My Letter to the Editor of 'Nature' follows:

Oversights in calculating when mitochondrial Eve lived

Cann et al calculated the rate of sequence divergence in human mtDNA by assuming that certain 'region-specific clusters' of these sequences in the aboriginal inhabitants of Australia, New Guinea and the New World had arisen in those countries and therefore could not be older than the first dates of settlement (1). Wilson and Cann later took these dates for Australia and New Guinea to be 50,000 to 60,000 years ago (2). They used the calculated rate to show when the most recent common mitochondrial ancestor of all humans ('Eve') lived.

I argue here that the assumed region-specific clusters of Australia, New Guinea and the New World arose in Asia, might be 500,000 or 600,000 y ears old, and became extinct in Asia after some of the people bearing them had migrated to Sahul and the New World. The people survived in Sahul and the New World because both of these huge regions were benign in climate and rich in food (except for Alaska , the colder parts of Canada and the deserts of Australia). Just as importantly, they were uninhabited until recently in human evolution and remained lightly settled until a few centuries ago, lessening the likelihood of one group of humans exterminating another in order to gain territory.

Most of the New World is more hospitable to human life than Siberia. It is easy to imagine some mtDNA clusters becoming extinct in the human population of Siberia but surviving and flourishing as the first settlers from Siberia and their descendants expanded into the New World.

The settlers of Sahul crossed a sea-channel at least 70 kilometres wide to get there from Asia, when the sea level had been lowered by the last ice age and the great continental shelf east of Asia was a plain. They were presumably a people who took food from the sea as well as the land, and who had sea-faring ability. Some of these sea-using people might have stayed behind on the ice-age coast of Asia, with the plain between them and high ground. That tropical plain was probably productive of food and fairly densely settled.

When the ice age ended and the sea rose it re-invaded the plain rather quickly, at the rate of a kilometre a year in places (3). In this situation the sea-using people on the Asian side of the sea-channel were vulnerable. The inhabitants of the land between them and high ground were not likely to give their territory to refugees driven westward by the invading coast, and the number of refugees would have increased year by year, century by century. The sea-using people might not have drowned, but many of them and their descendants would have been clubbed or speared to death in fights for living area that went on for scores of generations. It is likely that those of them capable of crossing the sea-channel would have made every effort to flee to Sahul.

The sea-using people that had settled in Sahul and their descendants were not vulnerable in the same way. Some of them might have migrated inland long before the sea began to rise, but Sahul was only lightly settled, and refugees from its re-invading coastline could move inland and find new territory without having to fight other human beings for their land. Thus some ancient mtDNA clusters might have been wiped out by the effects of the rising sea in eastern Asia but survived and flourished in Sahul.

If the apparently region-specific clusters of mtDNA sequences used by Cann et al originated as early as I suggest, the divergence rate calculated by those authors is 10 times too high and their 'mitochondrial Eve' must have lived about 1.5 million years ago, not about 150,000 years ago.

This matter will not be settled until laboratory methods are devised of comparing the net mutation rates of the mtDNA sequences of interest in humans and chimpanzees (I can think of two approaches to this problem).

The acquisition of language by humans conferred 'evolutionary leverage' on wise, knowledgeable and communicative old individuals through increased survival rates of their children and grandchildren. But this leverage could last only while the brain was vigorous and free from diseases, including those caused by mitochondrial mutations in brain cells. I suggest that natural selection in this situation greatly reduced the mitochondrial mutation rate in humans, perhaps to about a tenth of that calculated by Cann et al.

The arguments I have advanced above might also apply to some of the apparently region-specific alleles of nuclear genes.

References

1) Cann, R.L., Stoneking, M., & Wilson, A.C. Nature 325, 31-36 (1987).

2) Wilson, A.C. & Cann, R.L. Scientific American 264, 22-27 (1992).

3) Thorne, A. & Raymond, R. Man on the Rim, chapter 2, 28-47 (Angus & Robertson, Sydney, 1989).

Andrew Gyles

This letter was not published in 'Nature'. However, the Editor's guide for authors informs them that 'Nature' has space to publish only one in 10 of the letters to the Editor that it receives each week.

________________________________CONTENTS

On 17 February 2000 I sent a letter to the Editor of 'Nature', the weekly journal published in London, which had published in 1987 the paper that could be said to have started the 'Out of Africa' idea. This is the idea that modern humans evolved in Africa, some of them left Africa roughly 100,000 years ago, and these modern humans replaced all more primitive humans. My letter follows:

A lower mtDNA sequence divergence rate in humans?

If the multiregional hypothesis of human evolution turns out to be correct, as it yet might, we shall have to face the fact that the rate of 'mtDNA sequence divergence' in humans assumed by Cann, Stoneking and Wilson in their opposing so-called 'modern African Eve' hypothesis (1) was about 10 times too high.

They calculated that 'the mean rate of sequence divergence within humans lies between two and four per cent per million years... This rate is similar to previous estimates from animals as disparate as apes, monkeys, horses, rhinoceroses, mice, rats, birds and fishes'. From this they calculated that 'the common ancestor of all surviving mtDNA types existed 140,000-290,000 years ago'. More recently some proponents of this 'modern African Eve' hypothesis have suggested that the common mtDNA ancestor lived about 125,000 years ago; they have thus adopted a divergence rate of about 4.5% per million years.

However, if the alternative multiregional hypothesis is correct, the common mtDNA ancestor must have lived before humans left Africa between 1.5 and 2 million years ago, and the total mtDNA sequence divergence we see in living humans must have accumulated in that much longer period (roughly 10 times as long). We shall in that case have to ask the questions: Why should the mtDNA sequence divergence rate in humans be only a tenth of what it is in 'apes, monkeys, horses, rhinoceroses, mice, rats, birds and fishes'? Is this one of the elusive differences that make us human?

Andrew Gyles

Reference

1) R.L. Cann et al., Nature 325, 31-36 (1987).

________________________________CONTENTS

On 10th February 2000 I sent a letter to the Editor of 'Science', the weekly journal of the American Association for the Advancement of Science, published in Washington DC.

A lower mtDNA sequence divergence rate in humans?

I introduced the letter to the editor with a short note, part of which follows:

'The subject seems to me crucially important to biology. The tenfold difference in estimates of the mtDNA sequence divergence rate in humans cannot be reconciled by a compromise. If the actual rate in humans is only a tenth of that in, for example, chimpanzees, this might be one of the elusive things that make us human. My "Letter to the Editor of Science" follows:'

A lower mtDNA sequence divergence rate in humans?

Andrew Gyles

Reference

1) R.L. Cann et al., Nature 325, 31-36 (1987).

On 17th February 2000 I received a kindly letter from the editorial office of 'Science', which said in part:

'...we do not ordinarily consider Letters to the Editor of SCIENCE unless they comment on an item printed in SCIENCE within the past 6 months. In the case of your letter, we suggest that you submit it to a specialty journal or to the publisher of the article by Cann et al...'.

________________________________CONTENTS

Our deputy Neptune had no beard on his chin, and there was no trident to be seen standing in a corner anywhere, like an umbrella. But his hand was holding a pen -- the official pen, far mightier than the sword in making or marring the fortune of simple toiling men .

Joseph Conrad, 'The Shadow-line'