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Author
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Topic: The human and chimpanzee brains
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mark kennedy
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Member # 1870
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posted 24. January 2006 20:07
I'm new to the board but I was anxious to jump into the discussion with both feet. My interest is in the genetic basis for human evolution and I have been studying this subject (informally of course) for about a year now. I was interested in what the members thought of my thoughts on the genomic comparision of Chimpanzee and human genomes and gene expressions. Critical remarks and observations welcome, I would be very interested in hearing from someone knowledgable about the comparison of specific genes related to human/chimpanzee brain development and function.
When we discuss irreducible complex systems we generally think of things like enzymes, ribosomes, gila, bacteria flaggelum and hundreds of other biomolecular machines. I have developed an interest in the rise of something I have come to regard as the most irreducibly complex molecular machine in all of biology, the human brain.
Let us ponder the most significant questions confronting the single common ancestor model in our day. What makes us human? (Nature 437, 69-87 ) What is the genetic basis for the threefold expansion of the human brain in 2 1/2 million years?(Genetics, Vol. 165, 2063-2070) What is the genetic and evolutionary background of phenotypic traits that set humans apart from our closest evolutionary relatives, the chimpanzees?(Genome Research 14:1462-1473)
One of the problems with the evolutionary expansion of the human brain from that of an ape is the size, weight and complexity. The human brain would have had to triple in size, starting 2 1/2 million years ago and ending 200 to 400 thousand years ago. The brain weight would have had to grow by 250% while the body only grows by 20%. The average brain weight would have to go from 400-450g, 2 1/2 MY ago to 1350–1450 g 0.2–0.4 MY.
"It is generally believed that the brain expansion set the stage for the emergence of human language and other high-order cognitive functions and that it was caused by adaptive selection (DECAN 1992 ), yet the genetic basis of the expansion remains elusive."
Evolution of the Human ASPM Gene, a Major Determinant of Brain Size, Genetics, Vol. 165, 2063-2070, December 2003
Jianzhi Zhang tried to determine if positive selection of amino acid substitutions that left the reading frame open are detectable in the ASPM gene. He instead found strong purifying selection and concluded that the positive selection of the ASPM gene took place time between 6–7 and 0.1 MY ago (0.5 x 10,000 generations x 20 years/generation). Researchers have determined that the gene is still evolving but I wonder how a congenital developmental defect characterized by severely reduced brain size could be an advantage.
Overall genetic differences create a problem since the size of the genetic differences is growing. Type 'DNA similarities between humans and chimpanzees' into a google search engine and you will find estimates close to 99%. Growing evidence has determined that these estimates are just plain wrong. The divergence has been found to include indels of considerable length, in the comparison of the Chimpanzee Chromosome 22 and its counterpart Human Chromosome 21 found that 83% of chimpanzee chromosome 22 proteins are different from their human counterparts.
"Sakaki said their analysis found about 68,000 insertions or deletions. "That is almost one insertion/deletion every 470 bases," he said. In addition, a small proportion of genes showed a relatively higher rate of evolution than most other genes. "We haven't known what proportion of the genes shows adaptive evolution. This study shows it to be about 2 to 3%," he said."
Chimps are not like humans Whole-chromosome comparison reveals much greater genetic differences than expected
More recently, the Chimpanzee Genome project published their highly anticipated Initial sequence of the chimpanzee genome and comparison with the human genome, Nature 437, 69-87 (1 September 2005). What they found was the the differences between the chimpanzee and human genomes have a 35 million nucleotide difference with five million insertion/deletion events, and various chromosomal rearrangements. This would include a 3 million bp divergence in the function part of the genome effecting vital functions. Even by conservative estimates the fixation of single base substitutions, insertions, deletions and polymorphisms (including chromosomal rearrangements) would have to average anywhere from 3 to 7 bp differences, fixed in the respective genomes, per year for humans to evolve from apes. The most important of these would be the human brain with the most important changes occurring in the cerebral cortex.
For 150 years the consensus in the scientific community has been that human beings descended from some kind of an ape. The most likely candidate for our closest relative would be the chimpanzee since we have more in common with them then any of the other apes. In the September 2000 edition, Nature magazine printed an article that compared the entire genome of human beings to that of the chimpanzee and described the differences in great detail. What they found was approximately 35 million differences at a single-nucleotide level in addition to approximately 5 million indels (insertions/deletions). In order to understand the importance of these findings you have to consider what would have had to occur for human beings to share a common ancestor with the chimpanzee. Now in order for these 35 million differences to occur there would have had to be 3.5 mutations established genome wide per year for 10 million years.
35,000,000 differences in 10,000,000 years
3,500,000 differences in 1,000,000 years
350,000 differences in 100,000 years
35,000 differences in 10,000 years
3,500 differences in 1,000 years
350 differences in 100 years
35 differences in 10 years
3.5 differences per year
According to evolutionary theory we diverged from the chimpanzee about 10 million years ago (it was actually 5-7 million but I’m feeling generous). In that time there would have had to be 35 million differences accumulated genome wide. In the article they cite, ‘High genomic deleterious mutation rates in hominids’, published in Nature in 1999. In this article they proposed that there are 4.2 amino acid altering mutations per diploid per generation which they estimate to be about 20 years. They went on to say that 38% would be eliminated by natural selection leaving 1.6 new deleterious mutations. If you do the math then that is 8 mutations every 100 years and over a period of 10 million years it could only account for 800,000 differences.
8 every 100 years
80 every 1,000 years
800 every 10,000 years
8,000 every 100,000 years
80,000 every 1,000,000 years
800,000 in 10,000,000 years
Something is just not adding up here but wait it gets better. The most important of these changes would have had to occur in the last 2.5 million years. During that time the brain would have had to grow to 2.5 times the size of our supposed ancestors and also become 2.5 times denser. Even more recently the frontal lobes, believed to be essential for language, would have to have be developed.
We are all familiar with the famous double helix of Watson and Crick and since then the central dogma of biology has been DNA-Transcription-mRNA-Translation. You might remember from your basic biology class that when a cell replicates the first thing that happens is that a copy of the DNA is made by enzymes that unzips the double helix making two complimentary stands. This is the RNA that is transported to the ribosome where it is translated into proteins that become the building blocks of the cell. When you look at the double helix it resembles a spiral staircase and each of the steps would represent a single base pair. These nucleotides are grouped together in threes called codons that become the amino acids. The amino acids in turn become proteins and these proteins are built into cells, all of life works this way. When you change one or two of the nucleotides it will disrupt the reading frame, unless it’s in regions that are not involved in coding proteins.
Consumed with incredulity I started to wonder how the genes effecting brian function were related to the presumed common ancestor of Man and Chimpanzee. What I found was astonishing and I don't mean the differences between chimpanzees and humans, which are considerable. The differences within their respective species and, even more suprising, from one individual to another are far larger then I realized. In fact, 22% of the genes that showed differences between humans and chimpanzees where due to differences between individuals within their respective species.
What follows is from Regional Patterns of Gene Expression in Human and Chimpanzee Brains . Apparently the transcriptomes differ more between individuals then between regions. In comparing human and chimpanzee genes differ by 10% in at least one region with the majority being shared in all others. I will make every attempt not to exaggerate the differences nor dismiss the similarities. I, like most people interested in the theory of evolution, am interested in the genetic basis of evolution.
"The draft sequence of the chimpanzee genome will allow most nucleotide differences between the two species to be listed. However, to interpret these differences in terms of function, an important step is to know how gene expression has changed between humans and chimpanzees. Because several important phenotypic differences that distinguish humans and apes are associated with cerebral activity, it is of particular interest to investigate the gene expression patterns in brains of humans and chimpanzees."
Figure 1 Location of areas sampled from the human cerebral cortex.
The cerebral cortex in involved in many complex brain functions including memory, attention, perceptual awareness, "thinking", language and consciousness.
"In the cerebral cortex, the biggest difference in gene expression is between the primary visual cortex and the anterior cingulate cortex in both humans and chimpanzees, where 193 and 227 genes differ in expression in humans and chimpanzees, respectively."
The primary visual cortex has been observed to have distinct differences between chimpanzees and other primates considered to be related to humans. The human nonphosphorylated neurofilaments (NPNF) is denser with embedded cell bodies, were intermingled with lightly stained territories, giving the layer a mesh-like appearance. (Cerebral Cortex, Vol. 12, No. 7, 671-691, July 2002)
In other regions the differences are close to nonexistent.
"Only one gene out of the 4998 genes with detectable expression differs in expression between Broca's area and the left prefrontal cortex in all three humans analyzed and none in chimpanzees."
Figure 3 Number of genes exhibiting expression patterns specific to brain regions in humans and chimpanzees.
In all the differences amount to:
"406 differentially expressed genes for which the chimpanzee DNA sequence is known, 207 are more highly expressed in humans and 199 in chimpanzees."
What is the explanation that is most often used to explain the level of divergence in genes affecting the brain? Welcome to the wonderful world of duplications. Chromosomes 1, 2, 4, 5, 9, 12, 15, 16, 17, and 18, are known sites of significant differences between chimpanzees and humans. Instead of differences modern researchers simply insert the word selection instead of admitting the coding regions have distinct structural differences. In the conclusion they assume that these chromosomal rearrangements led to speciation because they lead to lower recombination in the heterokaryotypes.
"Gene expression differences between humans and chimpanzees are furthermore associated with regions of segmental duplications in the human genome Table 5 . This association is seen for genes that show higher expression levels in humans than in chimpanzees, whereas there is no statistically significant association with genes that are more highly expressed in chimpanzees."
When looking at this through the Darwinian prism it refracts and distorts the real world complications associated with natural selection. In order for natural selection to preserve an inheritable trait it must first be produced and the genetic basis for this extraordinary adaptive innovation remains elusive.
This statement from the Chimpanzee Genome Project paper in Nature left me dumbfounded:
"More than a century ago Darwin1 and Huxley posited that humans share recent common ancestors with the African great apes. Modern molecular studies have spectacularly confirmed this prediction and have refined the relationships, showing that the common chimpanzee (Pan troglodytes) and bonobo (Pan paniscus or pygmy chimpanzee) are our closest living evolutionary relatives."
This is simply not what the evidence is telling us and certainly not consistant with what Darwin and Huxley predicted. This is not slight, successive, gradual changes, this is an evolutionary giant leap. Affirming it requires a leap of faith philosophers call an a priori assumption.
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John A. Davison
Member
Member # 1425
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posted 25. January 2006 07:36
I agree that modern man has been a giant step but it was not made in a single event. I figure about 12 were required because that is the number of chromosome rearrangements that distinguish us from the chimpanzee, out closest living relative. None of these intermediate species survives and none of them were produced as a result of allelic mutation. Of that I am confident. I don't know how many times I have to say this but I see no role for chance in either ontogeny or phylogeny. Neither did Leo Berg:
"Neither in the one nor in the other is there room for chance."
Nomogenesis, page 406
That is the substance of the PEH concerning which I remain like a dog with a bone.
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Christopher D. Beling
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Member # 723
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posted 25. January 2006 19:58
Hi Mark,
This is a very interesting subject - thanks for the references. There seems, however, to be a problem with the URL for this reference:
Chimps are not like humans Whole-chromosome comparison reveals much greater genetic differences than expected
Hope you could correct it -thanks: Chris
[ 25. January 2006, 20:00: Message edited by: Christopher D. Beling ]
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mark kennedy
Member
Member # 1870
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posted 28. January 2006 23:00
I checked the link to 'Chimps are not like humans Whole-chromosome comparison reveals much greater genetic differences than expected', and I went right to it.
Also I had read the paper 'Davison Prescribed Evolutionary Hypothesis' before I posted my OP. I found it very interesting but I am most interested in the genetic basis for evolution.
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Christopher D. Beling
Member
Member # 723
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posted 30. January 2006 04:24
Hi Mark,
I have picked up that reference - thx - probably a problem on my PC. These 35 x10^6 mutational differences are quite a problem aren't they? According to the standard text-book understanding the mutation rate for higher organisms is 10^-10/bp/generation. If one takes a genome length of say 3x10^9 bp that gives a rate of 0.3/generation. If the mutations are mainly neutral then this would equate with an introduction rate per/population of 0.3/generation. But the generation length for a human or chimp is ~20 year giving an estimate mutation rate of .015 mutation/year (significantly less than 3.5). Could you check my calculation or comment on it?
Question; Are these mutations noted in the Nature paper neutral? If they occur largely on functional genes would one not expect to have a even lower mutational rate?
- Chris
[ 30. January 2006, 08:47: Message edited by: Christopher D. Beling ]
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mark kennedy
Member
Member # 1870
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posted 19. October 2006 21:22
quote:
Hi Mark,
I have picked up that reference - thx - probably a problem on my PC. These 35 x10^6 mutational differences are quite a problem aren't they? According to the standard text-book understanding the mutation rate for higher organisms is 10^-10/bp/generation. If one takes a genome length of say 3x10^9 bp that gives a rate of 0.3/generation. If the mutations are mainly neutral then this would equate with an introduction rate per/population of 0.3/generation. But the generation length for a human or chimp is ~20 year giving an estimate mutation rate of .015 mutation/year (significantly less than 3.5). Could you check my calculation or comment on it?
Question; Are these mutations noted in the Nature paper neutral? If they occur largely on functional genes would one not expect to have a even lower mutational rate?
- Chris
Sorry I took so long getting back, I had forgotten about this board and happened back here while doing a google search.
The mutation rate for hominids is usually around 2.7 * 10^-8 which translates into 123 mutations per human zygote. When comparing the DNA of humans and chimpanzees they are about 95% the same. Single nucleotide substitutions come to 35 million base pairs (Mb) indels are 90 Mb or 3-4% while the major chromosomal rearrangements are another 20 Mb which are from 2 Mb to 4 Mb. This whole buisness of Chromosome 2 showing a TAG right where they expected is misleading. There are actually 9 pericentric inversion hotspots and a lot more scattered throughout. That is at least what the Chimpanzee Consortium reported in Nature Magazine in September of 2005.
A genome-wide survey of structural variation between human and chimpanzee
The Initial seqeunce of the Chimpanzee Genome paper found over 500 genes out of over 13000 compared that had a Ka/Ks ratio that was >1 which is over 1/3. There were a total of 40,000 nucleotides that diverged which may seem like a slight amount but in highly conserved genes mutations are deadly.
Recently they have started exploring the Human Accelerated Regions, there are 49. The first one they looked at revealed a regulatory gene involved in the development of the cerbral cortex between the 7 and 17th week of gestation.
"Forty-nine regions, which the team called human accelerated regions (HARs), rose to the top of the list. Surprisingly, only two of these regions code for proteins. Instead, the majority of the regions tend to be located near genes that are involved in regulating the function of genes. Furthermore, 12 of the regions are adjacent to genes involved in the development of the brain.
The Nature paper looks in depth at the region that has undergone the most change in the human lineage, which the researchers called HAR1 (for human accelerated region 1). Only two of the region's 118 bases changed in the 310 million years separating the evolutionary lineages of the chicken and the chimp. Incredibly, since the human lineage separated from that of the chimp, 18 of the 118 nucleotides have changed. This region "stood out," said Pollard. "
Novel RNA gene is one of the fastest evolving regions in human genome
Dispite all of this Darwinians will tell you that there isn't much difference between humans and chimpanzees. If there is a more irreducibly complex system in the world then the regulatory genes involved in neural functions I don't know what it would be.
[ 19. October 2006, 21:25: Message edited by: mark kennedy ]
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