Chimpanzee Genome Project
Encyclopedia
The Chimpanzee Genome Project is an effort to determine the DNA
sequence of the Chimpanzee
genome
. It is expected that by comparing the genomes of humans and other apes, it will be possible to better understand what makes humans distinct from other species.
s are very similar. The primary difference is that humans have one fewer pair of chromosomes than do other great apes
. Humans have 23 pairs of chromosomes and other great apes have 24 pairs of chromosomes. In the human evolutionary lineage, two ancestral ape chromosomes fused at their telomere
s producing human chromosome 2
. There are nine other major chromosomal differences between chimpanzees and humans: chromosome segment inversions on human chromosomes 1
, 4
, 5
, 9
, 12
, 15
, 16
, 17
, and 18
. After the completion of the Human genome project
, a Common Chimpanzee genome project was initiated. In December 2003, a preliminary analysis of 7600 genes shared between the two genomes confirmed that certain genes such as the forkhead-box P2
transcription factor
, which is involved in speech development, are different in the human lineage. Several genes involved in hearing were also found to have changed during human evolution, suggesting selection involving human language
-related behavior. Differences between individual humans and Common Chimpanzees are estimated to be about 10 times the typical difference between pairs of humans.
on September 1, 2005, in an article produced by the Chimpanzee Sequencing and Analysis Consortium, a group of scientists which is supported in part by the National Human Genome Research Institute
, one of the National Institutes of Health
. The article marked the completion of the draft genome sequence. A database now exists containing the genetic differences between human and chimpanzee genes, with about thirty-five million single-nucleotide
changes, five million insertion/deletion events, and various chromosomal
rearrangements
. Gene duplication
s account for most of the sequence differences between humans and chimps. Single-base-pair substitutions account for about half as much genetic change as does gene duplication.
Typical human and chimp homologs
of protein
s differ in only an average of two amino acid
s. About 30 percent of all human proteins are identical in sequence to the corresponding chimp protein. As mentioned above, gene duplications are a major source of differences between human and chimp genetic material, with about 2.7 percent of the genome now representing differences having been produced by gene duplications or deletions during approximately 6 million years since humans and chimps diverged from their common evolutionary ancestor. The comparable variation within human populations is 0.5 percent.
About 600 genes have been identified that may have been undergoing strong positive selection in the human and chimp lineages; many of these genes are involved in immune system
defense against microbial disease (example: granulysin
is protective against Mycobacterium tuberculosis
,) or are targeted receptors of pathogenic microorganisms (example: Glycophorin C
and Plasmodium falciparum
). By comparing human and chimp genes to the genes of other mammals, it has been found that genes coding for transcription factors, such as forkhead-box P2 (FOXP2
), have often evolved faster in the human relative to chimp; relatively small changes in these genes may account for the morphological differences between humans and chimps. A set of 348 transcription factor genes code for proteins with an average of about 50 percent more amino acid changes in the human lineage than in the chimp lineage.
Six human chromosomal regions were found that may have been under particularly strong and coordinated selection during the past 250,000 years. These regions contain at least one marker allele
that seems unique to the human lineage while the entire chromosomal region shows lower than normal genetic variation. This pattern suggests that one or a few strongly selected genes in the chromosome region may have been preventing the random accumulation of neutral changes in other nearby genes. One such region on chromosome 7 contains the FOXP2
gene (mentioned above) and this region also includes the Cystic fibrosis transmembrane conductance regulator
(CFTR) gene, which is important for ion transport in tissues such as the salt-secreting epithelium of sweat glands. Human mutations in the CFTR gene might be selected for as a way to survive cholera
.
Another such region on chromosome 4 may contain elements regulating the expression of a nearby protocadherin gene that may be important for brain
development and function. Although changes in expression of genes that are expressed in the brain tend to be less than for other organs (such as liver) on average, gene expression changes in the brain have been more dramatic in the human lineage than in the chimp lineage. This is consistent with the dramatic divergence of the unique pattern of human brain development seen in the human lineage compared to the ancestral great ape pattern. The protocadherin-beta gene cluster on chromosome 5 also shows evidence of possible positive selection.
Results from the human and chimp genome analyses should help in understanding some human diseases. Humans appear to have lost a functional caspase
-12 gene, which in other primates codes for an enzyme that may protect against Alzheimer's disease
.
The results of the chimpanzee genome project suggest that when ancestral chromosomes 2A and 2B fused to produce human chromosome 2, no genes were lost from the fused ends of 2A and 2B. At the site of fusion, there are approximately 150,000 base pairs of sequence not found in chimpanzee chromosomes 2A and 2B. Additional linked copies of the PGML/FOXD/CBWD genes exist elsewhere in the human genome, particularly near the p end of chromosome 9
. This suggests that a copy of these genes may have been added to the end of the ancestral 2A or 2B prior to the fusion event. It remains to be determined if these inserted genes confer a selective advantage.
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
sequence of the Chimpanzee
Chimpanzee
Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...
genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
. It is expected that by comparing the genomes of humans and other apes, it will be possible to better understand what makes humans distinct from other species.
Starting the chimpanzee genome project
Human and chimpanzee chromosomeChromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s are very similar. The primary difference is that humans have one fewer pair of chromosomes than do other great apes
Great Apes
Great Apes may refer to*Great apes, species in the biological family Hominidae, including humans, chimpanzees, gorillas, and orangutans*Great Apes , a 1997 novel by Will Self...
. Humans have 23 pairs of chromosomes and other great apes have 24 pairs of chromosomes. In the human evolutionary lineage, two ancestral ape chromosomes fused at their telomere
Telomere
A telomere is a region of repetitive DNA sequences at the end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. Its name is derived from the Greek nouns telos "end" and merοs "part"...
s producing human chromosome 2
Chromosome 2 (human)
Chromosome 2 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second largest human chromosome, spanning more than 237 million base pairs and representing almost 8% of the total DNA in cells.Identifying genes on each...
. There are nine other major chromosomal differences between chimpanzees and humans: chromosome segment inversions on human chromosomes 1
Chromosome 1 (human)
Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 247 million nucleotide base pairs, which are the basic units of information for DNA...
, 4
Chromosome 4 (human)
125px|rightChromosome 4 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 4 spans more than 186 million base pairs and represents between 6 and 6.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area...
, 5
Chromosome 5 (human)
Chromosome 5 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 5 spans about 181 million base pairs and represents almost 6% of the total DNA in cells. Chromosome 5 is one of the largest human chromosomes, yet has one of the lowest gene...
, 9
Chromosome 9 (human)
125px|rightChromosome 9 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome, as they normally do with all chromosomes...
, 12
Chromosome 12 (human)
Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 143 million base pairs and represents between 4 and 4.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic...
, 15
Chromosome 15 (human)
right|frame|Human chromosome 15Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 106 million base pairs and represents between 3% and 3.5% of the total DNA in cells.Identifying genes on each chromosome is an...
, 16
Chromosome 16 (human)
125px|rightChromosome 16 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 16 spans about 90 million base pairs and represents just under 3 % of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic...
, 17
Chromosome 17 (human)
125px|rightChromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 81 million base pairs and represents between 2.5 and 3 % of the total DNA in cells.Identifying genes on each chromosome is an active area of...
, and 18
Chromosome 18 (human)
125px|rightChromosome 18 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 18 spans about 85 million base pairs and represents about 2.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic...
. After the completion of the Human genome project
Human Genome Project
The Human Genome Project is an international scientific research project with a primary goal of determining the sequence of chemical base pairs which make up DNA, and of identifying and mapping the approximately 20,000–25,000 genes of the human genome from both a physical and functional...
, a Common Chimpanzee genome project was initiated. In December 2003, a preliminary analysis of 7600 genes shared between the two genomes confirmed that certain genes such as the forkhead-box P2
FOXP2
Forkhead box protein P2 also known as FOXP2 is a protein that in humans is encoded by the FOXP2 gene, located on human chromosome 7 . FOXP2 orthologs have also been identified in all mammals for which complete genome data are available...
transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
, which is involved in speech development, are different in the human lineage. Several genes involved in hearing were also found to have changed during human evolution, suggesting selection involving human language
Language
Language may refer either to the specifically human capacity for acquiring and using complex systems of communication, or to a specific instance of such a system of complex communication...
-related behavior. Differences between individual humans and Common Chimpanzees are estimated to be about 10 times the typical difference between pairs of humans.
Draft genome sequence of the common chimpanzee
Analysis of the genome was published in NatureNature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...
on September 1, 2005, in an article produced by the Chimpanzee Sequencing and Analysis Consortium, a group of scientists which is supported in part by the National Human Genome Research Institute
National Human Genome Research Institute
The National Human Genome Research Institute is a division of the National Institutes of Health, located in Bethesda, Maryland.NHGRI began as the National Center for Human Genome Research , which was established in 1989 to carry out the role of the NIH in the International Human Genome Project...
, one of the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
. The article marked the completion of the draft genome sequence. A database now exists containing the genetic differences between human and chimpanzee genes, with about thirty-five million single-nucleotide
Point mutation
A point mutation, or single base substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA. Often the term point mutation also includes insertions or deletions of a single base pair...
changes, five million insertion/deletion events, and various chromosomal
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
rearrangements
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
. Gene duplication
Gene duplication
Gene duplication is any duplication of a region of DNA that contains a gene; it may occur as an error in homologous recombination, a retrotransposition event, or duplication of an entire chromosome.The second copy of the gene is often free from selective pressure — that is, mutations of it have no...
s account for most of the sequence differences between humans and chimps. Single-base-pair substitutions account for about half as much genetic change as does gene duplication.
Typical human and chimp homologs
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s differ in only an average of two amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s. About 30 percent of all human proteins are identical in sequence to the corresponding chimp protein. As mentioned above, gene duplications are a major source of differences between human and chimp genetic material, with about 2.7 percent of the genome now representing differences having been produced by gene duplications or deletions during approximately 6 million years since humans and chimps diverged from their common evolutionary ancestor. The comparable variation within human populations is 0.5 percent.
About 600 genes have been identified that may have been undergoing strong positive selection in the human and chimp lineages; many of these genes are involved in immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
defense against microbial disease (example: granulysin
Granulysin
Granulysin is a substance released by cytotoxic T cells when they are attached to infected body cells. It functions to create holes in the target cell membrane and destroy it...
is protective against Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
,) or are targeted receptors of pathogenic microorganisms (example: Glycophorin C
Glycophorin C
Glycophorin C plays a functionally important role in maintaining erythrocyte shape and regulating membrane material properties, possibly through its interaction with protein 4.1. Moreover, it has previously been shown that membranes deficient in protein 4.1 exhibit decreased content of glycophorin C...
and Plasmodium falciparum
Plasmodium falciparum
Plasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito. Malaria caused by this species is the most dangerous form of malaria, with the highest rates of complications and mortality...
). By comparing human and chimp genes to the genes of other mammals, it has been found that genes coding for transcription factors, such as forkhead-box P2 (FOXP2
FOXP2
Forkhead box protein P2 also known as FOXP2 is a protein that in humans is encoded by the FOXP2 gene, located on human chromosome 7 . FOXP2 orthologs have also been identified in all mammals for which complete genome data are available...
), have often evolved faster in the human relative to chimp; relatively small changes in these genes may account for the morphological differences between humans and chimps. A set of 348 transcription factor genes code for proteins with an average of about 50 percent more amino acid changes in the human lineage than in the chimp lineage.
Six human chromosomal regions were found that may have been under particularly strong and coordinated selection during the past 250,000 years. These regions contain at least one marker allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
that seems unique to the human lineage while the entire chromosomal region shows lower than normal genetic variation. This pattern suggests that one or a few strongly selected genes in the chromosome region may have been preventing the random accumulation of neutral changes in other nearby genes. One such region on chromosome 7 contains the FOXP2
FOXP2
Forkhead box protein P2 also known as FOXP2 is a protein that in humans is encoded by the FOXP2 gene, located on human chromosome 7 . FOXP2 orthologs have also been identified in all mammals for which complete genome data are available...
gene (mentioned above) and this region also includes the Cystic fibrosis transmembrane conductance regulator
Cystic fibrosis transmembrane conductance regulator
Cystic fibrosis transmembrane conductance regulator is a protein that in humans is encoded by the CFTR gene.CFTR is a ABC transporter-class ion channel that transports chloride and thiocyanate ions across epithelial cell membranes...
(CFTR) gene, which is important for ion transport in tissues such as the salt-secreting epithelium of sweat glands. Human mutations in the CFTR gene might be selected for as a way to survive cholera
Cholera
Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...
.
Another such region on chromosome 4 may contain elements regulating the expression of a nearby protocadherin gene that may be important for brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
development and function. Although changes in expression of genes that are expressed in the brain tend to be less than for other organs (such as liver) on average, gene expression changes in the brain have been more dramatic in the human lineage than in the chimp lineage. This is consistent with the dramatic divergence of the unique pattern of human brain development seen in the human lineage compared to the ancestral great ape pattern. The protocadherin-beta gene cluster on chromosome 5 also shows evidence of possible positive selection.
Results from the human and chimp genome analyses should help in understanding some human diseases. Humans appear to have lost a functional caspase
Caspase
Caspases, or cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases are a family of cysteine proteases that play essential roles in apoptosis , necrosis, and inflammation....
-12 gene, which in other primates codes for an enzyme that may protect against Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.
Genes of the Chromosome 2 fusion site
Chromosome 9 (human)
125px|rightChromosome 9 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome, as they normally do with all chromosomes...
. This suggests that a copy of these genes may have been added to the end of the ancestral 2A or 2B prior to the fusion event. It remains to be determined if these inserted genes confer a selective advantage.
- PGML. The phosphoglucomutasePhosphoglucomutasePhosphoglucomutase is an enzyme that transfers a phosphate group on an α-D-glucose monomer from the 1' to the 6' position in the forward direction or the 6' to the 1' position in the reverse direction....
-like gene of human chromosome 2. This gene is incomplete and may not produce a functional transcript. - FOXD. The forkhead boxFOX proteinsFOX proteins are a family of transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity...
D4-like gene is an example of an intronless gene. The function of this gene is not known, but it may code for a transcription control protein. - CBWD. Cobalamin synthetase is a bacterial enzyme that makes vitamin B12CyanocobalaminCyanocobalamin is an especially common vitamer of the vitamin B12 family. It is the most famous vitamer of the family, because it is, in chemical terms, the most air-stable...
. In the distant past, a common ancestor to mice and apes incorporated a copy of a cobalamin synthetase gene (see: Horizontal gene transferHorizontal gene transferHorizontal gene transfer , also lateral gene transfer , is any process in which an organism incorporates genetic material from another organism without being the offspring of that organism...
). Humans are unusual in that they have several copies of cobalamin synthetase-like genes, including the one on chromosome 2. It remains to be determined what the function of these human cobalamin synthetase-like genes is. If these genes are involved in vitamin B12 metabolism, this could be relevant to human evolution. A major change in human development is greater post-natal brain growth than is observed in other apes. Vitamin B12 is important for brain development, and vitamin B12 deficiency during brain development results in severe neurological defects in human children. - CXYorf1-like protein. Several transcripts of unknown function corresponding to this region have been isolated. This region is also present in the closely related chromosome 9p terminal region that contains copies of the PGML/FOXD/CBWD genes.
- Many ribosomalRibosomeA ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
protein L23a pseudogenePseudogenePseudogenes are dysfunctional relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell...
s are scattered through the human genome.
See also
- Common ChimpanzeeCommon ChimpanzeeThe common chimpanzee , also known as the robust chimpanzee, is a great ape. Colloquially, the common chimpanzee is often called the chimpanzee , though technically this term refers to both species in the genus Pan: the common chimpanzee and the closely related bonobo, formerly called the pygmy...
- Human evolutionary geneticsHuman evolutionary geneticsHuman evolutionary genetics studies how one human genome differs from the other, the evolutionary past that gave rise to it, and its current effects. Differences between genomes have anthropological, medical and forensic implications and applications...
- Human chromosome 2Chromosome 2 (human)Chromosome 2 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second largest human chromosome, spanning more than 237 million base pairs and representing almost 8% of the total DNA in cells.Identifying genes on each...
- Human Genome ProjectHuman Genome ProjectThe Human Genome Project is an international scientific research project with a primary goal of determining the sequence of chemical base pairs which make up DNA, and of identifying and mapping the approximately 20,000–25,000 genes of the human genome from both a physical and functional...