Is this true?

On Thu, 12 Feb 2004 00:41:38 +0000 (UTC), [email hidden]

(john) said:

I read this in an article. I had never heard this before.

a woman makes her full complement of eggs even before she is born, a man makes sperm throughout his
life. As a man ages, his sperm increasingly become copies of copies of copies, with a consequent
multiplication of DNA errors.

Yes it is. See, for example wellcome.ac.ukhg06f007.htmlOpen ↗

On Thu, 12 Feb 2004 00:41:38 +0000 (UTC), [email hidden]

(john) said:

I read this in an article. I had never heard this before.

a woman makes her full complement of eggs even before she is born, a man makes sperm throughout his
life. As a man ages, his sperm increasingly become copies of copies of copies, with a consequent
multiplication of DNA errors.

Yes, this is correct. This is sometimes referred to as "male driven evolution" since, from
generation to generation, most chromosome mutations will occur when the chromosome is in a male
rather than when it is in a female. Since Y-chromosomes are always in males they have the highest
mutation rate and since X-chromosomes spend 2/3 of their time in females and only 1/3 in males they
have the lowest mutation rate. In humans sperm are estimated, on average, to go through 6 times
more replications than eggs. William L Hunt

john said:

I read this in an article. I had never heard this before.

a woman makes her full complement of eggs even before she is born, a man makes sperm throughout
his life. As a man ages, his sperm increasingly become copies of copies of copies, with a
consequent multiplication of DNA errors.

It has been a long time since I took cytology, but If I recall correctly human females produce their
full complement of eggs by the age of 2 years. They are held at meiosis II until they are stimulated
to mature and complete meiosis. This could be one of the reasons that trisomy and monosomy is higher
in older women. Our meiotic system evolved in animals with generation times probably measured in
weeks. In humans the immature eggs sit around at meiosis II for years before the completion of
meiosis and getting the final haploid set of chromosomes. It is apparent that mistakes start to
happen the older the egg gets. By the age of 45 around 1% of the live births are trisomy 21. Most of
the other trisomies are lethal and are rarely observed except in spontaneous abortions.

It has been verified that mutations in sperm increase as the male ages. I don't know if it is all
due to the increased number of cell divisions.

Ron Okimoto

In Adam's Curse Brian Sykes says this:

"Over the last hundred generations, going back to well before the birth of Christ, the mitochondria
you got from your mother had experienced only 2,400 potentially risky cell divisions. Compare that
to your Y-chromosome, if you have one, which has been copied about five hundred thousand times over
the same period."

This is one of the reasons why he claims that men are doomed in the next 100,000-200,000 years
unless we evolve (naturally or articially) a new way of triggering men (instead of relying on the
genes carried in the Y-chromosone).

r norman <rsn_@_comcast.net> wrote in message news:<[email hidden]>...

Quoted message said:

(john) said:

I read this in an article. I had never heard this before.

a woman makes her full complement of eggs even before she is born, a man makes sperm throughout
his life. As a man ages, his sperm increasingly become copies of copies of copies, with a
consequent multiplication of DNA errors.

Yes it is. See, for example wellcome.ac.ukhg06f007.htmlOpen ↗

Thanks to everyone who answered. I read this in an article that said on average men are 3 years
older than the women they marry. A lot of it was a fluff article about a woman's ticking clock ect
so I questioned some of the data.

On Sat, 14 Feb 2004 17:41:26 +0000 (UTC),

Rick said:

In Adam's Curse Brian Sykes says this:

"Over the last hundred generations, going back to well before the birth of Christ, the
mitochondria you got from your mother had experienced only 2,400 potentially risky cell divisions.
Compare that to your Y-chromosome, if you have one, which has been copied about five hundred
thousand times over the same period."

This is one of the reasons why he claims that men are doomed in the next 100,000-200,000 years
unless we evolve (naturally or articially) a new way of triggering men (instead of relying on the
genes carried in the Y-chromosone).

Male mammals have been producing sperm for about 200 million years. The Y chromosome seems to have
done okay for at least that long. Why would anyone think that the males of one particular lineage
([censored] sapiens) are doomed after surviving millions of years of evolution? There are roughly 5000
different species of mammals, are they all doomed?

Larry Moran

Rick <[email hidden]> wrote or quoted:

Quoted message said:

In Adam's Curse Brian Sykes says this:

"Over the last hundred generations, going back to well before the birth of Christ, the
mitochondria you got from your mother had experienced only 2,400 potentially risky cell divisions.
Compare that to your Y-chromosome, if you have one, which has been copied about five hundred
thousand times over the same period."

This is one of the reasons why he claims that men are doomed in the next 100,000-200,000 years
unless we evolve (naturally or articially) a new way of triggering men (instead of relying on the
genes carried in the Y-chromosone).

Maleness is characterised by numerous, small mobile gametes.

I don't think there's much chance of the utility of those going away.
--
__________
|im |yler timtyler.orgtimtyler.orgOpen ↗ [email hidden] Remove lock to reply.

Rick said:

In Adam's Curse Brian Sykes says this:

"Over the last hundred generations, going back to well before the birth of Christ, the
mitochondria you got from your mother had experienced only 2,400 potentially risky cell divisions.
Compare that to your Y-chromosome, if you have one, which has been copied about five hundred
thousand times over the same period."

This is one of the reasons why he claims that men are doomed in the next 100,000-200,000 years
unless we evolve (naturally or articially) a new way of triggering men (instead of relying on the
genes carried in the Y-chromosone).

All mammals reproduce the same way. And have for millions of years.

--Jeff

--
Ho, ho, ho, hee, hee, hee and a couple of ha, ha, has; That's how we pass the day away, in the merry
old land of Oz.

[email hidden] (Rick) wrote in :"]news:[email hidden]:

Quoted message said:

In Adam's Curse Brian Sykes says this:

Quoted message said:

"Over the last hundred generations, going back to well before the birth of Christ, the
mitochondria you got from your mother had experienced only 2,400 potentially risky cell divisions.
Compare that to your Y-chromosome, if you have one, which has been copied about five hundred
thousand times over the same period."

Quoted message said:

This is one of the reasons why he claims that men are doomed in the next 100,000-200,000 years
unless we evolve (naturally or articially) a new way of triggering men (instead of relying on the
genes carried in the Y-chromosone).

I think this conclusion assumes that the Y canot correct mistakes. But check out this research:

"Instead, the Y appears to exchange genes between the two copies of repeated sequences that lie near
to each other as mirror images.

This phenomenon, called gene conversion - the non-reciprocal transfer of genetic information from
one DNA molecule to another -- has been previously observed on a small scale over long evolutionary
timescales between repeated sequences on the same chromosome, but not at the dramatic frequency
apparently employed by the Y chromosome. "

The article is at: genome.gov11007628Open ↗

If I read it right, it means that the Y is not as susceptible to mutation as was once thought.

Yours,

Bill Morse

Quoted message said:

Male mammals have been producing sperm for about 200 million years. The Y chromosome seems to have
done okay for at least that long. Why would anyone think that the males of one particular lineage
([censored] sapiens) are doomed after surviving millions of years of evolution? There are roughly 5000
different species of mammals, are they all doomed?

His take on this is that extinctions happen all the time so it could have happened to plenty of
species already. Some have got around the problem by switching to genes on other chromosomes to take
over the job of male development. He quotes the research on the mole vole, Ellobius lutescens, as an
example of a species that seems to have made the switch. The moles don't have a Y-chromosome ,
neither do they have the SRY gene. By switching the genes for male production to a different
chromosome he reckons that the new chromosome will eventually suffer the same fate as the Y-
chromosome but this species has given itself reprieve for tens of millions of years.

---
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William Morse <[email hidden]> wrote or quoted:

Quoted message said:

I think this conclusion assumes that the Y canot correct mistakes. But check out this research:

"Instead, the Y appears to exchange genes between the two copies of repeated sequences that lie
near to each other as mirror images.

This phenomenon, called gene conversion - the non-reciprocal transfer of genetic information from
one DNA molecule to another -- has been previously observed on a small scale over long
evolutionary timescales between repeated sequences on the same chromosome, but not at the dramatic
frequency apparently employed by the Y chromosome. "

The article is at: genome.gov11007628Open ↗

If I read it right, it means that the Y is not as susceptible to mutation as was once thought.

Very interesting ;-)

With a single backup copy, point mutations can potentially be undone.
--
__________
|im |yler timtyler.orgtimtyler.orgOpen ↗ [email hidden] Remove lock to reply.

Quoted message said:

Quoted message said:

In Adam's Curse Brian Sykes says this:

Quoted message said:

"Over the last hundred generations, going back to well before the birth of Christ, the
mitochondria you got from your mother had experienced only 2,400 potentially risky cell
divisions. Compare that to your Y-chromosome, if you have one, which has been copied about five
hundred thousand times over the same period."

Quoted message said:

This is one of the reasons why he claims that men are doomed in the next 100,000-200,000 years
unless we evolve (naturally or articially) a new way of triggering men (instead of relying on
the genes carried in the Y-chromosone).

I think this conclusion assumes that the Y canot correct mistakes. But check out this research:

"Instead, the Y appears to exchange genes between the two copies of repeated sequences that lie
near to each other as mirror images.

This phenomenon, called gene conversion - the non-reciprocal transfer of genetic information from
one DNA molecule to another -- has been

previously

Quoted message said:

observed on a small scale over long evolutionary timescales between repeated sequences on the same
chromosome, but not at the dramatic frequency apparently employed by the Y chromosome. "

The article is at: genome.gov11007628Open ↗

If I read it right, it means that the Y is not as susceptible to mutation as was once thought.

For the record for those who have not read Adam's Curse, there is a postscript that covers this. The
information only became available as the book was going to the printer. He claims this does not
affect his calculation because "Those calculations were based on empirical evidence of increasing
male infertility, irrespective of the molecular mechanism."

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Version: 6.0.588 / Virus Database: 372 - Release Date: 13/02/2004

Rick <[email hidden]> wrote or quoted:

Quoted message said:

Quoted message said:

The discovery that the information for some of the genes on the Y chromosome appears to be
encoded pallindromically is only a few months old, thus the information transmission system has
not been characterized in detail yet.

However, it would seem very unlikely that it could act as an error-recovery mechanism. When you
only have two copies of anything -- and they disagree -- there is no simple way to determine
which, if either, copy is correct.

Which raises the question, how is the "correct" gene selected when comparing between the one that
came from mother or the father?

Genes are swapped at random. Selection deals with those with more than their fair share of mutations
- and rewards those who by chance have a smaller-than-average load.

Quoted message said:

What is the difference between comparing the two versions of a gene in any paired chromosome to
comparing the two versions in the palindromic Y-chromosome?

The most obvious difference - as far as gene repair goes - is that all the chromosomes *except* the
Y have backup copies in /every/ member of the population.

The Y-chromosome has only got *one* backup copy to work from.

However that's still infinitely many more backups than had previously been thought ;-)
--
__________
|im |yler timtyler.orgtimtyler.orgOpen ↗ [email hidden] Remove lock to reply.

Quoted message said:

Quoted message said:

Quoted message said:

The discovery that the information for some of the genes on the Y chromosome appears to be
encoded pallindromically is only a few months old, thus the information transmission system
has not been characterized in detail yet.

However, it would seem very unlikely that it could act as an error-recovery mechanism. When
you only have two copies of anything -- and they disagree -- there is no simple way to
determine which, if either, copy is correct.

Which raises the question, how is the "correct" gene selected when comparing between the one
that came from mother or the father?

Genes are swapped at random. Selection deals with those with more than their fair share of
mutations - and rewards those who by chance have a smaller-than-average load.

I think you are talking about selection whereas I was talking about the "error-recovery mechanism".
What I meant was why is the "correct" gene dominant. I read somewhere that a mutated gene will be
recessive. Is that correct? If so, how does it decide which gene is mutated and is it the same
process for deciding which of the two copies in the Y-chromosome should be used?

On Wed, 18 Feb 2004 00:44:42 +0000 (UTC), Tim Tyler <[email hidden]>

Quoted message said:

Wirt Atmar <[email hidden]> wrote or quoted:

Quoted message said:

Tim, following Bill, writes:

Quoted message said:

Quoted message said:

> The article is at: genome.gov11007628Open ↗
>
> If I read it right, it means that the Y is not as susceptible to mutation as was once thought.

Very interesting ;-)

With a single backup copy, point mutations can potentially be undone.

The discovery that the information for some of the genes on the Y chromosome appears to be
encoded pallindromically is only a few months old, thus the information transmission system has
not been characterized in detail yet.

However, it would seem very unlikely that it could act as an error-recovery mechanism. When you
only have two copies of anything -- and they disagree -- there is no simple way to determine
which, if either, copy is correct.

That doesn't matter:

If you have suffered a point mutation and then swap genes at random when generating sperm, you will
produce 1/4 double-mutated offspring, 1/2 single mutated offspring - and 1/4 offspring with no
mutations.

That is enough to undo deleterious point mutations - and reverse the effect of Muller's ratchet.
--

Wirt Atmar's proposal that this may be a error-check/reject mechanism doesn't fit well with the few
facts known. Between chimp and human Y genes there is about 3% divergence in spacer, a 2%
divergenece in standard genes and a 1.5% divergence for genes with palindromes. This looks like it
is more likely a selection based mechanism, at least it does to me. There is also some evidence
from neutral SNP's that it is selection based. It is not clear to me where Tim thinks the selection
is occurring but some may think that the very slight variation in the Y genes between sons (from
swapping with the palindromes) may be enough to overcome Muller's rachet. It is not enough.
Selection between adult males will not do it. If this is a selection based mechanism it must be
happening at a lower level. Since these genes with palindromes are expressed in testes, it may be
the selection is occurring in the process of spermatogenesis. For instance, if the the cells that
generate sperm are variant (from swapping between the expressed genes and unexpressed palindromes),
then those with fewer slightly deleterious mutations might generate more sperm than those with more
mutations. This would overcome or at least lessen the effect of Muller's rachet. This means the
sperm would not have Tim's 1/4 - 1/2 -1/4 frequency but something selectively skewed so there were
less than 1/4 "double-mutated" and more than 1/4 with no mutations even though the cells generating
these sperm did initially have a 1/4-1/2-1/4 frequency. This swapping between expressed gene and
unexpressed palindrome needs to be better understood. For instance, where and when exactly is this
swapping taking place, in meiosis or mitosis or both? William L Hunt

Quoted message said:

__________
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Rick <[email hidden]> wrote or quoted:

Quoted message said:

Quoted message said:

Quoted message said:

> However, it would seem very unlikely that it could act as an error-recovery mechanism. When
> you only have two copies of anything -- and they disagree -- there is no simple way to
> determine which, if either, copy is correct.

Which raises the question, how is the "correct" gene selected when comparing between the one
that came from mother or the father?

Genes are swapped at random. Selection deals with those with more than their fair share of
mutations - and rewards those who by chance have a smaller-than-average load.

I think you are talking about selection whereas I was talking about the "error-recovery
mechanism".

I was talking about the error-recovery mechanism as well.

The error recovery mechanism necessarily involves selection.

Without selection there is no way to tell which gene is the mutated one.

Quoted message said:

What I meant was why is the "correct" gene dominant.

I never said it was - and it may not be.

Quoted message said:

I read somewhere that a mutated gene will be recessive. Is that correct?

/Often/ it is. Mutated genes often code for non-functional proteins - which are naturally recessive.

Quoted message said:

If so, how does it decide which gene is mutated [...]

"It"? The one that doesn't work is the mutated one.

Quoted message said:

and is it the same process for deciding which of the two copies in the Y-chromosome should
be used?

No. If anything, the fact that mutated genes are often recessive hinders their correction - by
concealing their effects.
--
__________
|im |yler timtyler.orgtimtyler.orgOpen ↗ [email hidden] Remove lock to reply.

Tim Tyler <[email hidden]> wrote in message news:<[email hidden]>...

Quoted message said:

Rick <[email hidden]> wrote or quoted:

Quoted message said:

Quoted message said:

> > However, it would seem very unlikely that it could act as an error-recovery mechanism.
> > When you only have two copies of anything -- and they disagree -- there is no simple way
> > to determine which, if either, copy is correct.
>
> Which raises the question, how is the "correct" gene selected when comparing between the one
> that came from mother or the father?

Genes are swapped at random. Selection deals with those with more than their fair share of
mutations - and rewards those who by chance have a smaller-than-average load.

I think you are talking about selection whereas I was talking about the "error-recovery
mechanism".

I was talking about the error-recovery mechanism as well.

The error recovery mechanism necessarily involves selection.

Without selection there is no way to tell which gene is the mutated one.

Quoted message said:

What I meant was why is the "correct" gene dominant.

I never said it was - and it may not be.

Quoted message said:

I read somewhere that a mutated gene will be recessive. Is that correct?

/Often/ it is. Mutated genes often code for non-functional proteins - which are naturally
recessive.

Quoted message said:

If so, how does it decide which gene is mutated [...]

"It"? The one that doesn't work is the mutated one.

OK. Therefore Wirt Atmar's statement "When you only have two copies of anything -- and they disagree
-- there is no simple way to determine which, if either, copy is correct." is false.

Rick <[email hidden]> wrote or quoted:

Quoted message said:

Tim Tyler <[email hidden]> wrote in message news:<[email hidden]>...

Quoted message said:

Rick <[email hidden]> wrote or quoted:

Quoted message said:

Quoted message said:

Quoted message said:

> > > However, it would seem very unlikely that it could act as an error-recovery mechanism.
> > > When you only have two copies of anything -- and they disagree -- there is no simple way
> > > to determine which, if either, copy is correct.
> >
> > Which raises the question, how is the "correct" gene selected when comparing between the
> > one that came from mother or the father?
>
> Genes are swapped at random. Selection deals with those with more than their fair share of
> mutations - and rewards those who by chance have a smaller-than-average load.

I think you are talking about selection whereas I was talking about the "error-recovery
mechanism".

I was talking about the error-recovery mechanism as well.

The error recovery mechanism necessarily involves selection.

Without selection there is no way to tell which gene is the mutated one.

Quoted message said:

What I meant was why is the "correct" gene dominant.

I never said it was - and it may not be.

Quoted message said:

I read somewhere that a mutated gene will be recessive. Is that correct?

/Often/ it is. Mutated genes often code for non-functional proteins - which are naturally
recessive.

Quoted message said:

If so, how does it decide which gene is mutated [...]

"It"? The one that doesn't work is the mutated one.

OK. Therefore Wirt Atmar's statement "When you only have two copies of anything -- and they
disagree -- there is no simple way to determine which, if either, copy is correct." is false.

He did say "simple".

Selection can tell which genes have been zapped - but to do that it has to grow them into a whole
organism and see how well they reproduce compared to their fellows - hardly a *simple* process.

I human watcher can sometimes tell whether a gene has been mutated by seeing if it codes for a known
useful protein - or comparing it with expected data - but again, this isn't a *simple* process.

It's true that - given two copies of a gene you can't /easily/ tell which one is the right one.

Selection can tell, though - and a "backup copy" may well allow an organism with a mutation on one
bit of their Y chromosome to still be able to have some offspring without that mutation.
--
__________
|im |yler timtyler.orgtimtyler.orgOpen ↗ [email hidden] Remove lock to reply.

Tim Tyler <[email hidden]> wrote in message news:<[email hidden]>...

Quoted message said:

Rick <[email hidden]> wrote or quoted:

Quoted message said:

Tim Tyler <[email hidden]> wrote in message news:<[email hidden]>...

Quoted message said:

Rick <[email hidden]> wrote or quoted:

Quoted message said:

Quoted message said:

> > > > However, it would seem very unlikely that it could act as an error-recovery mechanism.
> > > > When you only have two copies of anything -- and they disagree -- there is no simple
> > > > way to determine which, if either, copy is correct.
> > >
> > > Which raises the question, how is the "correct" gene selected when comparing between the
> > > one that came from mother or the father?
> >
> > Genes are swapped at random. Selection deals with those with more than their fair share of
> > mutations - and rewards those who by chance have a smaller-than-average load.
>
> I think you are talking about selection whereas I was talking about the "error-recovery
> mechanism".

I was talking about the error-recovery mechanism as well.

The error recovery mechanism necessarily involves selection.

Without selection there is no way to tell which gene is the mutated one.

> What I meant was why is the "correct" gene dominant.

I never said it was - and it may not be.

> I read somewhere that a mutated gene will be recessive. Is that correct?

/Often/ it is. Mutated genes often code for non-functional proteins - which are naturally
recessive.

> If so, how does it decide which gene is mutated [...]

"It"? The one that doesn't work is the mutated one.

OK. Therefore Wirt Atmar's statement "When you only have two copies of anything -- and they
disagree -- there is no simple way to determine which, if either, copy is correct." is false.

He did say "simple".

I'm not trying to win points - just trying to understand.

Quoted message said:

Selection can tell which genes have been zapped - but to do that it has to grow them into a whole
organism and see how well they reproduce compared to their fellows - hardly a *simple* process.

I human watcher can sometimes tell whether a gene has been mutated by seeing if it codes for a
known useful protein - or comparing it with expected data - but again, this isn't a *simple*
process.

It's true that - given two copies of a gene you can't /easily/ tell which one is the right one.

Selection can tell, though - and a "backup copy" may well allow an organism with a mutation on one
bit of their Y chromosome to still be able to have some offspring without that mutation.

In paired chromosomes there is a gene on each chromosome and somehow one is switched on and the
other switched off. Presumably something similar happens on the Y-chromosome. If so I can't
appreciate the difference. Can we think of some examples? What about the gene that causes red-green
colour-blindness? In a female with one normal and one colour-blind gene the normal one is dominant
(there doesn't seem to be any problem picking the right one). What happens in a male? There is only
one X chromosome so only one copy of the gene. If the gene does not code for a "known useful
protein" what happens? Does the colour-blind gene code a useful protein? The gene presumably is used
regardless because I can see colours although not perfectly. If colour-blindness is not a mutation
then what is it? I've used colour-blindness as an example but there could be a new thread about it
as it raises so many interesting questions like why hasn't it been eliminated by selection and why
is it more prevalent in western cultures.

When I originally read the phrase "error correction mechanism" I thought it meant that the good gene
would be dominant instead of the faulty gene or that when the Y-chromosome has recombination with
itself it corrects the faulty gene. But you interpretted it as meaning that the faulty gene is
weeded out by selection. I don't see why you haven't considered that error correction could happen
in the Y-chromosome because if a correct gene can be chosen for dominancy then it could be chosen to
correct an error on the other copy in the Y-chromosome. I assume that no-one knows for certain as
this is leading edge research.