The Chimpanzee Genome

As an aside, does anyone know if Fazale R. Rana,
Ph.D. has had any comment about the information
published in 2005 (see commentary about it below)
since the 2001 article "Humans and Chimps
Differ" in Hugh Ross' Connections 2001 - Volume
3, Number 3 posted
here?: http://www.reasons.org/resources/connections/2001v3n3/index.shtml

I haven't been able to find anything. ~ Janice

Thursday, September 01, 2005

The chimpanzee genome

<http://pharyngula.org/index/member/1/>PZ Myers •
17
<http://pharyngula.org/index/weblog/comments/the_chimpanzee_genome/#comments>Comments
http://64.233.179.104/search?q=cache:SvBbphfO81oJ:pharyngula.org/index/weblog/comments/the_chimpanzee_genome/+Has+a+genome-wide+comparison+of+humans%E2%80%99+and+chimps%E2%80%99+DNA+ever+been+made%3F&hl=en&gl=us&ct=clnk&cd=1

I finished reading the chimpanzee genome paper
last night, and it is not an easily digestible
piece of work. It's fairly technical genetics,
and it's actually a bit of a hodge-podge, as you
might expect given the multitude of authors and the immensity of the project.

In many places where the results were
particularly interesting, the authors also got
very cautious and tentative, and quite rightly so:

this is just the first step in a very difficult
research program, and there aren't any simple,
clear answers to be expected…not yet, if ever.

I'm not even going to try to present a narrative
summary of the work. The best I can do is dole
out some little tidbits that I thought were interesting.

The sequence as a whole was obtained from a
single specimen of Pan troglodytes. However, they
also analyzed sequences from four other West
African and three Central African chimps.

Humans and chimps are much more alike than
different. 29% of our proteins are identical, and
the average protein differs by only two amino
acids. The genome wide nucleotide divergence rate
is 1.23% (it's higher in the Y chromosome, which
seems to be a special case­see
<http://johnhawks.net/weblog/reviews/chimpanzees/genetics/y_chromosome_chimpanzee_comparison_2005.html>John
Hawks).

While single nucleotides are different in 1.23%
of the genome, 3% differs because of insertions
and deletions; that is, largish chunks of DNA
that are missing in one species relative to the
other, or that have been added in one. The
authors estimate that there have been about 5
million insertions and deletions in the combined
chimp and human lineages in the last 5-7 million years since they diverged.

Most of the differences are the result of the
fixation of neutral or slightly deleterious alleles.

One common question is which differences are
important; which genetic changes are responsible
for the obvious differences between chimps and
humans? Of the 13,454 human-chimp gene
orthologues they examined, they identified 585
that have a high level on non-synonymous sequence
changes, and examined their function, where known.

If you were hoping for an obvious 'big brain' or
'hairy-limb' gene, you will be disappointed. What
they found were genes involved in:

immune responses, for instance against malaria and tuberculosis

reproduction, protamines and semenogelins

olfaction

That's what's important, humbling as it may be.

A search by functional category for relative
acceleration in the rate of non-synonymous
substitutions did find one interesting
difference: humans have a greater than expected
difference in genes involved in transcription
factor activity. This includes some homeotic genes.

This suggests that there may have been important
changes in developmental regulatory genes in the
human lineage, but because the absolute number of
nucleotide changes is small, the authors suggest
some caution about overinterpreting this at this point.

36 human genes are not present at all in the
chimp, and and additional 17 are partially deleted.

There are also genes present in chimps that are
missing or damaged in humans, but deficiencies in
the gene models for chimps makes them more difficult to quantify.

One very interesting example is caspase-12, an
important enzyme in apoptosis, which triggers
cell death in response to problems in calcium levels.

Humans have a damaged copy of the gene, while
that of chimps and mice is intact. Loss of
function in mice leads to a failure of
amyloid-induced neuronal cell death; this may be
a gene that contributes to Alzheimer's disease in humans.

Another interesting analysis was to compare human
alleles associated with disease to the chimp
orthologues. As it turns out, some alleles we
consider 'bad', or disease-related, are the
wild-type forms. For example, a form of the gene
called PPARG that has a proline at position 12 is
associated with a greater risk of type 2 diabetes
in humans, but is the most common allele in
chimps. That suggests that the diabetes-resistant
form of PPARG is the recent adaptation, and that
we may be seeing the ongoing spread of this allele in our population.

The authors identified evidence of selective
sweeps in human history. Alleles that are
selectively successful can rise rapidly in
frequency in a population. Because recombination
in any one region is relatively rare, when that
allele becomes fixed, the other alleles that
happen to be in the gene locations around it will
also be fixed in the population. This process
reduces diversity and also increases the
frequency of a whole set of hitchhiking alleles in that same region.

Comparison with the chimpanzee genome as a
baseline allowed the authors to pick out 6
regions in the human genome that exhibit all the
signs of having been subject to a selective sweep
within the last quarter million years. One of
these regions contains both the
<http://www.corante.com/loom/archives/000811.html>FOXP2
gene, involved in speech, and the CFTR gene
which, when defective, is responsible for cystic fibrosis. ..." [snip]

NOTE: Pharyngula has moved to http://scienceblogs.com/pharyngula/
Received on Thu Mar 2 11:28:45 2006