Re: Human Genome May Be Longer Than Expected

Stephen E. Jones (sejones@iinet.net.au)
Fri, 06 Aug 1999 06:37:27 +0800

Reflectorites

On Sun, 01 Aug 1999 11:48:12 +0000, mortongr@flash.net wrote:

[...]

>SJ>which is claiming that the human genome might have a billion more genes
>>than previously thought. If that is true, what becomes of claims that we
>>share 98% of our genes with chimps? Doesn't this show that we would
>>have to sequence both ours' and the chimps' genomes to know for sure?

First, it has been pointed out to me by a biologist on the other list I am on,
my "billion more genes" is a mistaken interpretation. The article said
"chemical units", by which is meant *nucleotide base-pairs*, not genes.
The actual number of extra genes was not actually given in the article but it
does say that "The human genome may be...one-third larger than
previously thought..." and that "the number of human genes is likely to lie
at the higher end of the range usually quoted -- 60,000 to 100,000".

The usual previous estimate for the human genome was 100,000 genes:

"The human genome contains very roughly 100 000 genes..." (White A.,
"The greatest apes", New Scientist, 15 May 1999.
http://www.newscientist.co.uk/ns/19990515/thegreates.html)

so an additional "one-third" could mean an extra 33,000 genes!

Even the old 2% difference was a problem for Darwinism. 2% of 100,000
genes is 2,000 different genes, let alone how they are confifured. A
geneticist on the other list I am on wrote:

"I have long said that even a 98% identity does not reflect well for
evolution. If there are 100,000 genes, then a crude comparison means that
there are the equivalent of 2,000 novel genes separating humans and
chimps. 5 million years is very little time to accumulate that much change in
species such as humans and chimps that exhibit such long generation times,
few offspring, low reproductive rate, wide-ranging migration patterns, and
generalized diets. I haven't done the math, but this is an extremely large
hurdle to overcome."

If 2,000 new genes is already a problem for Darwinism, an additional
*33,000* genes would *really* be a problem! But of course, it may turn
out that when the human and chimp genomes are completely sequenced,
the relative 2% difference may remain.

But my expectation is that when the human genome is completely mapped,
a large number of novel genes will be found. There will then be pressure to
map the chimps' genome too, in order to see if they occur in what is thought
to be man's closest living relative. I expect it will then be found to everyone's
astonishment that a large number of new genes will remain in the human
genome that are not homologous with chimps or in fact any apeandfound
in chimps.

If this happens it would represent yet another blow to Darwininism, and of
course it would be consistent with a Mediate Creation model in which an
Intelligent Designer creates by modifying existing genetic blueprints.

GM>Nothing happens to that claim. The claim was made using standard sampling
>techniques and didn't involve a base-pair by base-pair comparison. If they
>had done that, it would have been noticed earlier that the genome might be
>a bit longer. Sampling techniques are done all the time and are fairly
>accurate at assessing things.

Glenn is not be correct here that "The claim was made using standard
sampling techniques", at least in the original 1975 study by King & Wilson:

"Moving on from immune reactions to proteins to the DNA itself, which
orders the shape of the proteins, Wilson and another student, Marie-Claire
King, showed that chimp and man are 99 per cent identical." (King M.-C.
& Wilson A.C., 'Evolution at two levels in humans and chimpanzees",
Science, 188: 107-116, 1975, in Gribbin J. & Cherfas J., "The Monkey
Puzzle", 1982, p262).

Gribbin and Cherfas explain that the process used for comparing the
percentage difference between different species' DNA was DNA
hybridisation (aka DNA annealing). Gribbin and Cherfas explain:

"...it would still be nice to make- that final step and come down from the
amino acid sequence to the DNA itself, but just as the fingerprint technique
is intermediate between immune response and amino acid sequence, so too
there is a technique that is intermediate between amino acid sequence and
nucleotide sequence. It is called DNA hybridisation.

The idea behind DNA hybridization is simplicity itself. We separate the
double helix of one species' DNA into its component single complementary
strands. We do the same to the DNA of the species we wish to compare it
with. Then we mix all the separated strands together. Where the two
species have identical sequences along their DNA, the complementary
bases from the two different species will be able to come together and
join...we would also find in our sample an equal amount of DNA in which
one strand had come from one sample and the other from the other, but
unless we had previously labelled one of the lots of DNA we would not be
able to tell which double-stranded molecule was which. If one sample had
been made highly radioactive, and if we could count the radioactivity of
each newly-formed double helix we would find that a quarter of the
molecules were as radioactive as the original sample, and another quarter
were not at all radioactive. if the two samples were very similar, so that
long stretches of each did indeed contain almost the same sequence of
eases, then they would still be able to form so-called hybrid molecules...

What we then want to know is the extent of the similarity, the percentage
of the two DNAs that is in fact identical. To do this we make use of the
fact that it is only the binding between individual pairs of complementary
bases that holds the two strands together. The more bonds there are, the
harder it will be to separate the strands of the hybrid DNA, and to measure
the strength of the bonding between the strands we need only put in energy
to overcome the binding energy and see when the strands drift apart. What
we are really doing is finding the melting point of the DNA. Solids are held
together by bonds between their component atoms. Inject energy into the
solid, in the form of heat, and you break the bonds so that the solid is free
to become a liquid. The energy needed to break the molecular bonds is the
melting point of the substance. To get back to DNA, if the two strands are
totally complementary they will be held together with a certain strength and
it will take a certain amount of energy, a temperature of around 85 degrees
Celsius, to separate them. If the strands are only partially complementary
the force holding them together will be weaker and it will take less energy,
a lower temperature, to make them drift apart. Impure DNA, in the sense
of being made of non-identical strands, has a lower melting point than pure
DNA, just as impure water has a lower melting point (freezes at a lower
temperature) than pure water...

The first step, as we've said, is to purify the DNA from the two species.
Then, one species' DNA is labelled with a radioactive tag, usually the
radioactive isotope of iodine; this does not affect the way the strands work,
but simpler acts as a tracer that enables researchers to follow the single
strands from that species. With the labelling done, the two sets of DNA are
mixed and slowly heated. At around 85 degrees Celsius the bonds between
opposite bases, which normally hold the strands together, are broken, and
the strands drift apart. Now the mixture is allowed to cool slowly so that
heteroduplex molecules can form from the two species of DNA. Once the
mixture is cooled the few remaining single strands are removed and the
business of measuring the melting point begins. The temperature is raised
by about one degree and the dissociates DNA removed and assayed for
radioactivity with an improves version of the old-fashioned geiger counter.
Then the temperature is raised another notch and the next lot of single
strands removed ant counted. A repeated series of counts at steadily
increasing tempera turns produces a so-called dissociation curve, the peak
of which represents the melting point of the hybrid DNA. This can then be
compared directly with the melting point of a pure hybrid, that is DNA
from the target species heated and allowed to recombine, so that any quirks
due to the heating processes and so on are evened out. The size of the
difference in melting points between heteroduplex and normal DNA is
directly related to the dissimilarity between the two strands. A difference of
one degree Celsius is roughly equivalent to a difference in one per cent of
the DNA; one in a hundred of the nucleotides are not identical in two
species that show a melting point depression of one degree Celsius....

Heteroduplex DNA made from Pan troglodytes and Homo sapiens melts at
a temperature just one degree Celsius below that of pure Homo sapiens
DNA. Ninety-nine out of a hundred bases are identical in man and the
chimp, which are not put in the same genus, or even the same family."

(Gribbin J. & Cherfas J., "The Monkey Puzzle", 1982, pp96-99)

But Gribbin & Cherfas admit that DNA annealing is not as accurate as
actually counting the DNA nucleotide sequences themselves:

"DNA annealing is a very powerful technique, but like protein
fingerprinting it is a step away from the information we are really after. The
ultimate truth resides not in the melting point of mixed DNA molecules but
in the sequence of bases along the DNA itself. These are the dice that
evolution rolls, and here we will find the successful moves that set one
species off from another. Technology, again, is everything. If you've
managed to extract the particular bit of DNA you are interested in from a
variety of species, pure enough and in sufficient amounts to work with,
actually uncovering the sequence of nucleotides is probably the easiest part
of the whole business. That doesn't mean that it is simple, but such
advances have been made in the genetic engineer's toolkit that one can
think realistically of knowing the entire nucleic acid sequence of an
organism. Indeed this has already been achieved, notably for the virus
phiX174 whose complete DNA sequence occupied several pages of the
scientific journal Nature in 1980...

The entire DNA sequence of a virus is much shorter than a human genetic
blueprint, and molecular biologists are still a long way from being able to
write down the DNA sequence for a man, or any other mammal. But the
technique is essentially a refinement of the molecule chopping and
reconstruction techniques used to sequence pro thins. DNA molecules are
cut into pieces, labelled with radioactive tracer atoms, the fragments
separated from one another by electrophoresis, and the sequence
reconstructed. Of course the work is more difficult than protein
sequencing, operating on a smaller molecular scale. It is rather as if we had
described how to make a grandfather clock and then said that making a
Cartier watch involved the same physics. It does, but our statement doesn't
do justice to the watchmaker's craft, just as we cannot do justice here to
the work of Wally Gilbert and Fred hanger. For our purposes all that
matters is that once the complete sequence of nucleotides along the DNA
of different species is known, the evolutionary history of those species can
be explored right down at the very level at which evolutionary changes take
place."

(Gribbin J. & Cherfas J., 1982, pp100-101)

I cheerfully concede of course that Glenn *might* be eventually proved
right that "Nothing happens to that claim", that "we share 98% of our
genes with chimps". But I do not concede that Glenn *will* be eventually
proved right about this claim. Until the human and chimp genomes are
completely mapped, no one really knows how distant each genome is from
the other.

The fact is that as genomes are completely mapped, researchers are finding
an unexpectedly high number of new genes which are unique to that
genome. For example in a 1997 article in NATURE, reporting on the first
eucaryote genome completely mapped, that of yeast (Saccharomyces
cerevisiae), Clayton, et. al., said:

"Faced with this wealth of new information about a time-honoured genetic
'model organism', Dujon has asserted that the most remarkable finding of
the yeast genome project is the discovery of 2,000 yeast genes of unknown
function, and with no homologues of known function." (Clayton R.A.,
White O., Ketchum K.A. & Venter J.C., "The first genome from the third
domain of life", Nature, Vol 387, 29 May 1997, p459)

and

"It is important to remember that there are many genes that do not appear
in this diagram. Like the orphan Saccharomyces cerevisiae genes, these
absentees appear to be unique to one genome. With such a small set of
common genes, and so many unique genes, we are led to question the
concept of S. cerevisiae or E. coli as model organisms- that is,
physiological representatives of many other organisms. In a real sense,
organisms that contain unique constituent parts cannot be models for one
another. Having several whole genomes spread out for our examination
underscores how different from one another these organisms are." (Clayton
R.A., et. al., 1997, p462)

Steve

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"Biologists must constantly keep in mind that what they see was not
designed, but rather evolved." (Crick F.H.C., "What Mad Pursuit: A
Personal View of Scientific Discovery", [1988], Penguin Books: London
UK, 1990, reprint, p138)
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