Question: How to recognize mutations
Bloopen...@juno.com
variation from most of its pals in its population. Is there a way that
we can tell that this variation is the result of mutation and not
recombination of existing genetic material, transposons, or gene
transference?
So for example, there's the famous story about peppered moths adapting
to the industrial revolution. Was this really the result of mutations,
or could it have been recombination of existing alleles? And how do we
know?
ErikW
Ask yourself why you call it alleles.
Scooter the Mighty
> Okay, suppose we find an organism with a noticeable phenotypic
> variation from most of its pals in its population. Is there a way that
> we can tell that this variation is the result of mutation and not
> recombination of existing genetic material, transposons, or gene
> transference?
Those are types of mutation. Mutation is just a change in genetic
sequence.
Ernest Major
Bloopen...@juno.com writes
>Okay, suppose we find an organism with a noticeable phenotypic
>variation from most of its pals in its population. Is there a way that
>we can tell that this variation is the result of mutation and not
>recombination of existing genetic material, transposons, or gene
>transference?
You appear to have a too narrow concept of what is a mutation.
If a tranposon disrupts a gene, or changes the regularatory control of a
gene, then that's a mutation.
If a gene is moved from one chromosome to another, then that's a
mutation.
If a gene is transferred from mitochondrion to nucleus (IGT) or from one
species to another (HGT, LGT) that that's a mutation.
Even intragenic recombination would be a mutation if it resulted in a
new allele.
Phenotypic traits can be tracked to genetic differences (e.g.
sickle-cell trait/anaemia, which results from a single amino-acid
substitution in haemoglobin). These can be identified, but you can't
readily tell whether an aberrant individual found in the world is a
mutant, a recombinant, or the result of a developmental anomaly.
However one shrub that I grow showed a tiny-fleck of yellow on a leaf,
and something about it told me that this was a mutant, and not the
result of disease. By the dint of careful pruning away of wild-type
shoots, and vegetative propagation, I know have 5 partially variegated
plants, and with luck, in a years time, I will have fully variegated
plants. In this case I can be sure that it's a mutant, as neither
meiosis nor development (from seed) is involved.
>
>So for example, there's the famous story about peppered moths adapting
>to the industrial revolution. Was this really the result of mutations,
>or could it have been recombination of existing alleles? And how do we
>know?
>
--
Alias Ernest Major
CreateThis
>Okay, suppose we find an organism with a noticeable phenotypic
>variation from most of its pals in its population. Is there a way that
>we can tell that this variation is the result of mutation
By seeing if it's passed on hereditarily.
>and not
>recombination of existing genetic material, transposons, or gene
>transference?
These are mutations.
CT
Perplexed in Peoria
"Ernest Major" <{$to$}@meden.demon.co.uk> wrote in message news:0$eaXqKnw...@meden.invalid...
Good answer. I would also point out that you can be sure that it was a
recent point mutation rather than ordinary 'crossing-over' recombination
IF you look at the genetic sequences of the child and both parents. This
has been done often enough so that we have a pretty good idea as to how
frequently particular kinds of point mutations happen. And then our
informed assumptions about mutation frequency can be plugged into the
analysis of things like the peppered moth study (in which, in general,
we DON'T do a careful comparison of each offspring to its parents).
r norman
There is a point to the question. Something like industrial melanism
could easily have resulted with absolutely no mutation or alteration
in the DNA whatsoever. It could be simply a change in the frequency
of existing alleles, or a change in the frequency of particular allele
combinations. A "novel" phenotypic feature can easily result from a
novel combination of existing alleles. Transposons and gene
transference are, indeed, forms of mutation but even those do not
result from the development of "new genetic information" but merely
from the rearrangement of already existing sequences.
Although I strongly suspect an ulterior motive in the question, it
still is a valid molecular biological point. The easiest way now to
detect "novel genetic information" (i.e. the sort of mutation I
believe the questioner is asking about) is through sequence analysis,
finding a DNA sequence that is not present in other members of the
species.
Robert Carnegie
How do you prove that without testing the DNA of every member of the
species?
For that matter, the gene sequence that produces the "new" biology is
likely to be a mutation of genes that the other individuals, without
the "new" characteristic, have.
r norman
<rja.ca...@excite.com> wrote:
"Perplexed" already answered your first point: all you really need
show is that the sequence is not present in the parents.
I don't understand your second point, that the alleles responsible for
the "new" biology is likely to be a mutation in other individuals.
Ultimately, all biological novelty is generated by mutations and the
production of new alleles. Then those alleles can recombined in
different ways to produce additional novelty resulting from gene
combinations. Some of those recombinations are simple shuffling from
sexual reproduction. Others involve crossover or other chromosomal
rearrangements that are a still a form of mutation. My point is
simply that "novel" biological features can result from the novel
combination of existing alleles far separated in time and space from
the origin of those alleles. In other words, the identification of
the origin of a specific "novel" feature means doing a lot of
molecular biological work. Ultimately it boils down to mutations
somewhere and at some time, just not necessarily here and now.
Luminoso
In that particular case you could do a genome analysis or
even something cruder like breed the black & white moths
and do some math on their progeny.
Full or partial genome sequencing can reveal much, although
it's a bit slow and expensive right now. The dif between
black & white moths, or dark or light people for that
matter, CAN be a matter of alleles, outright mutations or
processes that affect gene expression such as methylation.
Regardless though, it's POSSIBLE to find out. Whether you
can AFFORD to find out is another issue ...
r norman
wrote:
The more important issue is whether anybody would be interested in
finding out. If the question is important enough, someone will
eventually persuade the funding agencies to loosen some dollars. If
the issue is Parkinson's or Alzheimer's or diabetes or some other
such, then you can be sure people are hard at work looking. If the
issue is moths turning dark, then you can pretty sure that nobody
would even bother setting a grad student on it (unless either the
major professor or the grad student was particularly obnoxious).
Bloopen...@juno.com
> On Fri, 20 Apr 2007 19:05:01 GMT, lumin...@everywhere.net (Luminoso)
Okay, thanks for your answers everyone. So would I be correct in
saying that any process that results in the creation of a new allele
is by definition a mutation?
There is no ulterior motive to my question, i.e., I am not a troll who
is going to come blazing in here thinking he knows it all better than
99% of scientists. I manifestly don't. What got me thinking about it
is, as r norman pointed out, a new phenotypic characteristic could
develop because of a different combination of pre-existing alleles
that get shuffled around in sexual reproduction (right?). That's a
factor we need to account for whenever we point to modern-day examples
of adaptation.
A related question: I have a popular science book on genetics and
evolution. It contradicts itself, saying in one place that all genetic
variation is the result of mutations at some point, and in another
that's it's mostly due to recombination during meiosis, with rare
mutations. So which is it?
Ernest Major
Bloopen...@juno.com writes
In the short term the majority of genetic variation is due to
recombination and chromosomal assortment creating new combinations of
genes. In the long term every allele of every gene originated by a
mutation.
--
alias Ernest Major
Perplexed in Peoria
<Bloopen...@juno.com> wrote in message news:1177169315.8...@e65g2000hsc.googlegroups.com...
I think so.
> There is no ulterior motive to my question, i.e., I am not a troll who
> is going to come blazing in here thinking he knows it all better than
> 99% of scientists. I manifestly don't. What got me thinking about it
> is, as r norman pointed out, a new phenotypic characteristic could
> develop because of a different combination of pre-existing alleles
> that get shuffled around in sexual reproduction (right?). That's a
> factor we need to account for whenever we point to modern-day examples
> of adaptation.
>
> A related question: I have a popular science book on genetics and
> evolution. It contradicts itself, saying in one place that all genetic
> variation is the result of mutations at some point, and in another
> that's it's mostly due to recombination during meiosis, with rare
> mutations. So which is it?
It depends on what phenomenon you are trying to explain. Mutation is
more important in creating new alleles. Or rather, those kinds of mutation
which don't involve recombination are more important than the kinds of
mutation involving recombination. Only a tiny fraction of the new alleles
that appear result from crossing-over.
On the other hand, if you want an explanation for why your set of genes
is different from that of any of your ancestors, and different from
everyone else on earth, then recombination is the better explanation.
That is, mutation creates new genes; recombination creates novel sets of
genes. As slogans go, this one doesn't distort reality too badly.
Luminoso
Given current technology and the time/expense of using
it I fully agree. Moths aren't important enough. Much
better to just put the issue on hold and persue some
of the afflictions you listed.
Eventually though, sequencing WILL become much cheaper
and quicker. There's unbounded motivivation for finding
these new techniques - and a giant wad of cash for those
who do, which always seems to increase motivation and
willingness to take risks investing in new technology.
Oh yes, there IS a negative side-effect to quick, cheap
genetic sequencing. It was touched-on in a film entitled
"Gattaca". If a technology CAN be abused by the wealthy
and powerful, bet that it WILL be abused.
Mutations and such ...
It's a bit fuzzy when talking about "alleles" and "mutations".
In a sense an allele is a sort of modular "standard mutation",
one of several little genetic packages that can assert
themselves or not or in part. Having a time-tested pre-packaged
sequence always onboard that can alter an animals coloring or
size or a number of other phenotypic traits is definitely
a competetive advantage. Environmental conditions change
constantly so it's "wise" for a species to always have some
small sub-populations where the alternative phenotypes are
dominant. If your trees turn from white to black, a few
percent of the species will survive, enough to rapidly
replenish population numbers.
It's not entirely wrong to say that all humans are "mutants"
relative to each other. There is no "standard human" from a
genetic standpoint. Even "identical" twins develop unique
methylation patterns. With hundreds, thousands, of traits
as obvious as size or skin color to inobvious differences
in biochemistry, this much variation helps guarentee that
the "AVERAGE human", the "race", can adapt and survive
when faced by a large variety of environmental challenges.
The WORST scenerio would be herr Hitlers vision of a
single "pure" line of humans. Reducing variability below
a certain point is an open invitation to extinction the
moment "something" happens.
True, random, mutations always happen, although the results
are rarely "good" in any context. The random, or relatively
random, nature of mutation is a kind of "shotgun" approach
to introducing more variability. Only those very few mutations
that prove useful over time are likely to persist, perhaps to
eventually become packaged as an allele for, say, blue eyes
or a stocky heat-conserving build.
Robert Carnegie
Luminoso wrote:
But not only is it not worth spending more money on finding scientific
evidence to persuade creationists to accept the theory of evolution,
it's also unconstitutional.
Really, nothing remains to be proved; but you could chase moths for a
hundred years and not change a single mind. We're /done/ with the
moths.
Something more compelling maybe... say an early draft of the bible
showing sources. Maybe buried in the pyramid of an ancient Egyptian
science fiction publisher... "To Dr. Asimov: your youthful enthusiasm
for the genre does you credit, but we do not think that this work will
find a market as it stands. The time that the 'Newcomers' spend in
Egypt are not only counter-factual but inauthentic and will put off
any reader who took an ancient history class, and the 'ark' sequence
was clearly lifted from Velikovsky. We do like the two comic androids
at the start though - they could even have a pictogram series of their
own!"
Ron O
We now have the ability to sequence the DNA and check it out. The
problem is that genomes are large and we first have to figure out what
is the cause and where it is located. Before we had this ability we
would have to infer it from genetics. It isn't 100%. For the moth
example it was known that dark morphs were already present in the
population before the shift in allele frequency occurred. We know
that there are several different genetic means to achieve a dark morph
so it isn't a simple single gene mutation, but several genes are
involved. It is actually fairly difficult to determine what the
change in the DNA was. You first have to figure out what gene to look
at, and then have to figure out what the original sequence was. So
let's say that you find out what genes were involved (they haven't
figured this out, yet). You would then obtain the DNA sequence of
those genes from the various dark morphs and light morphs. You would
have to compare these sequences to closely related species to try and
determine what the ancestral sequence was. You obviously can't go by
allele frequency because you know that at one time the dark morphs
dominated and at other times light morphs dominated. You have to use
inferences from the fact of common descent and what you find is
"normal" gene function.
It isn't easy.
Sometimes you can just go by observation and DNA sequence
verification. An example is streptomycin antibiotic resistance in
bacteria. Decades ago they found out that a single base-pair change
in a ribosomal gene could produce a bacterium that was resistant to
the antibiotic. All you had to do to confrim this was to find
bacteria that were not resistant, clone them and grow up a lot of
bacteria from a single cell with a known DNA sequence and then hit
them with antibiotic and pick out the rare ones that were now
resistant. When they sequenced them they found that most of them had
the same single base-pair mutation that they had already figured out
before. As long as you can replicate the experiment and rule out
contamination you get your answer.
Another example is in humans there is a genetic condition called
achondroplastic dwarfism. It is dominant. This just means that
whenever you inherit the polymorphism or a new mutation, it is seen in
all individuals that carry it. Two normal parents routinely produce
new dwarf mutants. It is one of the highest mutation rates for a
single position in the genome that we know of. Around 1 in 14,000
life births have a new mutation at this locus that is dominantly
expressed and is the identical mutation found in nearly all
achondroplastic dwarfs. You know the parents do not have this base
substitution, but when you sequence the FGFR3 gene of the dwarf
progeny you find it.
No one denies that mutations happen. If all you want to do is blow
smoke and claim that we can't tell that mutations happened in the
past, who cares, and who would believe you? We have learned a lot
about mutation and recombination and when we look at the variation
within and between populations that is all we see evidence of. We
expect a lot of sequence variation in populations for the simple
reason that you can't prevent mutations from occurring. A population
will eventually reach what we call mutation selection balance where
the detrimental effects of mutation restrict their frequency due to
selection against them. This isn't a fine and narrow restriction
where only a few mutations are allowed, but a whole boatload. Humans
are a special case because they have less variation that we expect.
It is proposed that genetic bottlenecks occurred where the human
population decreased to very few breeding individuals, so inbreeding
has led to a loss of genetic variation from our population. Most
other species like chimps did not suffer such a bottle neck, even
though they may be suffering such today, and they have around 5 times
the genetic variation found in humans. This is a lot of genetic
variation. Any two relatively unrelated humans will vary by 1 in a
1000 base-pairs (0.1% difference) in single nucleotide type
mutations. Any two chimps will vary by 0.4-0.5% from each other and
any human and any chimp will vary by less than 1.5% from each other.
Mutations are a fact of life there is no way that we know of to stop
them from happening, not only that but the same ones will keep
happening. Every human inherited around 200 new mutations from their
parents scattered around the genome. If we say that there are over 6
billion people in the world, we are talking about 1.2 trillion new
mutations just in the extant population. Everyone has around 6
billion base-pairs of DNA in their genomes so every position in the
genome may have been hit a couple hundred times with new mutations.
We would expect that every single nucleotide mutations that could
occur probably did occur just in the extant population. The only ones
that we don't expect to observe are the dominant lethal mutations.
Ron Okimoto
hersheyh
> Okay, suppose we find an organism with a noticeable phenotypic
> variation from most of its pals in its population. Is there a way that
> we can tell that this variation is the result of mutation and not
> recombination of existing genetic material, transposons, or gene
> transference?
Yes. Geneticists have been doing this for years. But *all* variation
in genes is necessarily a consequence of change (mutation) in genes at
some point in time. Some of these variant mutations are
*phenotypically* dominant and others are *phenotypically* recessive.
[There are intermediate phenotypic possibilties as well.] That is, in
a heterozygote of a diploid organism, either the mutant phenotype will
be observed or the non-mutant phenotype will be observed; that is how
"dominance" or "recessiveness" is determined.
> So for example, there's the famous story about peppered moths adapting
> to the industrial revolution. Was this really the result of mutations,
> or could it have been recombination of existing alleles? And how do we
> know?
The melanic variant allele is *dominant*. That means that, whenever
the mutation to melanism occurs, it *immediately* affects the
phenotype of the organism. The *mutation* to a melanic variant allele
had been observed from time to time before the time of
industrialization as a *rare* event. The melanic variants were rare
and disappeared from these pre-industrial local moth populations
(because the melanic variant is detrimental in such an environment).
It was the change in the environment that made the melanic variant,
when it occurred, "beneficial" wrt reproductive success relative to
the non-melanic w.t. variant and allowed it to spread so rapidly.
But, the 'recessive' non-melanic variant allele remained in the
population as a minor fraction of the alleles because the
heterozygotes were phenotypically melanic. *Selection* works against
*phenotype*, not genotype. Thus Mm heterozygotes, because they look
just like MM homozygotes, are selectively identical to them and
different from the mm homozygotes.
So, recessive alleles (due to mutation) can lie 'hidden' at low levels
in populations, even when they would be deleterious as homozygotes.
If conditions change such that these recessive homozygotes are now
beneficial, the frequency of the recessive allele may also spread, but
more slowly than in the case where the 'new' beneficial allele is
dominant.
Luminoso
<rja.ca...@excite.com> wrote:
An interesting assertion, with some truth to it under
certain conditions. I would definitely be illegal for
federal/state/local governments to fund research with
the specific, stated, aim of de-bunking or confirming
someones religious beliefs. However, a more general
"knowledge-gathering" research program that JUST HAPPENEND
to generate such data, well, that's the way the cookie
crumbles.
Given the sheer number of religions, and you may even
have to count historical religions for fear of insulting
someones ancestry, it's just impossible to conduct most
ANY kind of biological research (or chemistry, physics,
astronomy, neurology or ...) without risk of stepping
on someones theological toes. One hint that the universe
was NOT barfed-up by the Great Cozmik Goat and you've
"insulted" SOMEBODYS beliefs.
As it's suicidal for government NOT to invest in science
and technology I suppose the attitude must be "Step on
anyones toes and damn the criticism".
>Really, nothing remains to be proved; but you could chase moths for a
>hundred years and not change a single mind. We're /done/ with the
>moths.
We'll get the specific info on the moths eventually.
Might be something interesting about their particular
situation. Not today however.
>Something more compelling maybe... say an early draft of the bible
>showing sources. Maybe buried in the pyramid of an ancient Egyptian
>science fiction publisher... "To Dr. Asimov: your youthful enthusiasm
>for the genre does you credit, but we do not think that this work will
>find a market as it stands. The time that the 'Newcomers' spend in
>Egypt are not only counter-factual but inauthentic and will put off
>any reader who took an ancient history class, and the 'ark' sequence
>was clearly lifted from Velikovsky. We do like the two comic androids
>at the start though - they could even have a pictogram series of their
>own!"
His mummy will be SO disappointed to hear of
the rejection letter. Tell them to stick that
papyrus where the Ra don't shine ! :-)
ErikW
> On 20 Apr 2007 07:01:33 -0700, ErikW <bryoph...@hotmail.com> wrote:
>
> >On Apr 20, 3:48 pm, Bloopenblop...@juno.com wrote:
snip
> >> So for example, there's the famous story about peppered moths adapting
> >> to the industrial revolution. Was this really the result of mutations,
> >> or could it have been recombination of existing alleles? And how do we
> >> know?
>
> >Ask yourself why you call it alleles.
>
> There is a point to the question. Something like industrial melanism
> could easily have resulted with absolutely no mutation or alteration
> in the DNA whatsoever. It could be simply a change in the frequency
> of existing alleles, or a change in the frequency of particular allele
> combinations. A "novel" phenotypic feature can easily result from a
> novel combination of existing alleles.
As you already know, existing alleles are also the result of a
mutation one way or another. Witohut a change in the genome s. lat.,
no change in the phenotype. Remember we're not talking about
populations but individuals here. As you already know.
> Transposons and gene
> transference are, indeed, forms of mutation but even those do not
> result from the development of "new genetic information" but merely
> from the rearrangement of already existing sequences.
To me this just illustrates why "genetic information" as a concept has
rather limited utility for me.
>
> Although I strongly suspect an ulterior motive in the question, it
> still is a valid molecular biological point. The easiest way now to
> detect "novel genetic information" (i.e. the sort of mutation I
> believe the questioner is asking about) is through sequence analysis,
> finding a DNA sequence that is not present in other members of the
> species.
Often, or perhaps even usually, especially for phenotypic evolution,
natural selection has been described as acting on existing variation
as opposed to having to wait for mutations. I think most hold this
view for phenotypic evolution even though molecular evolution seem to
be mutation driven.
ErikW
Perplexed in Peoria
"ErikW" <bryo...@hotmail.com> wrote in message news:1177337062.7...@n76g2000hsh.googlegroups.com...
> Often, or perhaps even usually, especially for phenotypic evolution,
> natural selection has been described as acting on existing variation
> as opposed to having to wait for mutations. I think most hold this
> view for phenotypic evolution even though molecular evolution seem to
> be mutation driven.
Well, of course natural selection acts on existing variation. It couldn't
very well act on non-existing variation, could it?
The issue is that natural selection tends to 'use up' or 'consume' the
existing variation. Variation is the 'fuel' of natural selection, and
if you want the process to continue, you need a continuing source of
new fuel. And not just any kind of variation. It needs to be heritable
variation.
Mutation is one important source of new heritable variation. Recombination
or 'crossing-over' is also an important source of new variation, but it
is my impression that much of the variation which comes from recombination
is not heritable. What recombination puts together, recombination will
probably tear apart again within a few generations.
r norman
I used to describe in my classes that mutation was "the most
important factor in evolutionary change" and, simultaneously, that
mutation was "the least important factor." (I would still do so, but
have now retired from teaching.)
It is the least significant because evolution is defined as a change
in the genetic composition of a population and mutation changes the
allele frequency by such a tiny amount that it is insignificant
compared to the other factors that change allele frequency.
It is the most significant because without variation there is no
evolution and mutation is ultimately the only source of variation.
It is quite possible for existing variation in a population to be
expressed in a completely novel way by a particular combination of
genes acquired through recombination in sexual reproduction to produce
a new phenotype completely without the immediate action of mutation.
Mutation, of course, was how the existing variation was produced.
However it is not at all how that phenotype was produced -- no single
gene was responsible for it.
Bloopen...@juno.com
All right, thanks for your help guys. I really appreciate it.
ErikW
wrote:
> "ErikW" <bryoph...@hotmail.com> wrote in messagenews:1177337062.7...@n76g2000hsh.googlegroups.com...
> > Often, or perhaps even usually, especially for phenotypic evolution,
> > natural selection has been described as acting on existing variation
> > as opposed to having to wait for mutations. I think most hold this
> > view for phenotypic evolution even though molecular evolution seem to
> > be mutation driven.
>
> Well, of course natural selection acts on existing variation. It couldn't
> very well act on non-existing variation, could it?
As regards molecular evolution there has been (still exist) a debate
if it is selection or mutation driven. The tentative consensus from
the data is that when a substitution in a protein is selected,
selection has usually had to "wait" for the mutation and it has not
been selected from an existing pool of mutations when a change in
environment or such happened.
Since many or most phenotypic traits we look at are polygenic we might
expect it to be otherwise on the phenotypic level. That is indeed the
view held by most. It is however not a given.
Maybe I didn't understand the original question cause I still don't
see how the follow up comments improved (much) on my one-liner answer.
> The issue is that natural selection tends to 'use up' or 'consume' the
> existing variation.
Sure, but not for many phenotypic traits since they are polygenic.
There is enough variation for selection to work on. (I do not see why
recombination is something special, we all would agree that
recombination it's the usual case in sexual organisms. One combination
of alleles from different loci gíves something different than another.
One can leave it at that for the sake of the original question. If we
on the other hand have recombination within a locus then you can
indeed get new variation, new alleles, but I don't think we are
talking about that.)
> Variation is the 'fuel' of natural selection, and
> if you want the process to continue, you need a continuing source of
> new fuel. And not just any kind of variation. It needs to be heritable
> variation.
>
> Mutation is one important source of new heritable variation. Recombination
> or 'crossing-over' is also an important source of new variation,
Personally I'd strike the word new in the preceeding sentence. We
don't know which combination came first after all.
> but it
> is my impression that much of the variation which comes from recombination
> is not heritable. What recombination puts together, recombination will
> probably tear apart again within a few generations.
(I may misunderstand you here but..) That depends on the nature of the
gene interactions and also on linkage which is influenced not only by
chromosomal physical proximity, but also by population processes,
including selection. I take it that's why you said "much"?
(If this goes any further I think we'll have to start getting careful
about how we use "genes" and "alleles").
And just to go to the OP once more, if we're still interested in that,
the dark colour of those butterflies is heritable.
ErikW