Sequencing the chimpanzee genome: insights into human evolution and disease

Key Points

  • The sequencing of the chimpanzee genome is now under way. Substantial data are expected to be available by the summer of 2003.

  • Because the last common ancestor of chimpanzees and humans lived only 5 million years ago, the comparison of the chimpanzee and human genome sequences provides an unprecedented opportunity to examine the genetic changes that are associated with the rapid evolution of new phenotypic characteristics.

  • Genetic differences between chimpanzees and humans are of significant medical interest as they might help to explain the distinctive set of disease susceptibilities seen in humans.

  • Approximately 95% of the chimpanzee genome seems to align directly with corresponding regions of the human genome and within these aligned segments, sequence divergence is only 1.2%.

  • Comparison of the chimpanzee and human genome sequences offers our best hope of looking back at the genetic changes that shaped modern humans.

  • One hypothesis about the evolution of modern humans emphasizes the importance of regulatory mutations, whereas another predicts that loss-of-function mutations on the human lineage were important in the phenotypic divergence of chimpanzees and humans. The chimpanzee genome sequence will facilitate tests of both hypotheses.

  • Genome sequencing of another great ape, preferably the gorilla, will be necessary to determine whether particular genetic differences occurred on the chimpanzee or the human lineage.

  • Evidence indicates that chimpanzees and humans have significantly different patterns of common disease.

  • Because of ethical constraints on the use of chimpanzees as experimental animals, alternative approaches will be required to develop the comparative biology of chimpanzees and humans. These approaches should include much more comprehensive capture of records of the veterinary care provided to captive chimpanzees.

  • Full use of the chimpanzee genome sequence will depend on greatly expanded studies of great ape phenotypes.


Large-scale sequencing of the chimpanzee genome is now imminent. Beyond the inherent fascination of comparing the sequence of the human genome with that of our closest living relative, this project is likely to yield tangible scientific benefits in two areas. First, the discovery of functionally important mutations that are specific to the human lineage offers a new path towards medical benefits. Second, chimpanzee–human comparisons are likely to yield molecular insights into how new biological characteristics evolve — findings that might be relevant throughout the tree of life.

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Figure 1: Sequence-based phylogenetic tree for the human and the great apes.


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Correspondence to Maynard V. Olson.

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Orang-utans, gorillas, chimpanzees and bonobos.


The densely staining regions of the nucleus that generally contain condensed, transcriptionally inactive regions of the genome.


The lightly staining regions of the nucleus that generally contain decondensed, transcriptionally active regions of the genome.


The process whereby a genetic variant arises by mutation and then increases in frequency in a population until it is the only variant present.


A protein that is a key transporter of the thyroid hormones in the blood and cerebrospinal fluid. Thyroid hormones stimulate an increase in the metabolic rate of many cell types and have effects on embryonic brain development.


The steady accumulation of mutations during evolution, which provides a basis for dating the point at which two contemporary species diverged from a common ancestor.


The elimination of deleterious mutations through natural selection.


An acidic sugar that is commonly found at the ends of the glycan chains of cell-surface glycoproteins and glycolipids. They are negatively charged under physiological conditions, contribute to biophysical characteristics of cell surfaces and can be recognized by many receptors of endogenous and exogenous origin.


A dispersed, intermediatly repetitive, 300-bp DNA sequence present in the human genome.


A mutation that results in a change in the reading frame of a protein-encoding region. Frameshift mutations frequently cause such marked changes in a protein sequence that the protein is completely inactivated.


A mutation that results in the introduction of a stop codon to cause the premature termination of a protein. Nonsense mutations often completely inactivate a protein.


A mutation in the coding region of a gene that changes the amino acid inserted at a particular position in a protein.


Monkeys that are native to Africa and Asia.


A type of cancer that originates from epithelial cells. Most human cancers other than leukaemias or lymphomas are carcinomas.


A pregnancy resulting from an abnormal fertilization event whose product can expand through successive cell divisions but cannot undergo normal development.


Raw data that are produced during DNA sequencing. An electropherogram displays the fluorescence produced by DNA molecules that have been electrophoretically separated during the DNA sequencing process.

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Olson, M., Varki, A. Sequencing the chimpanzee genome: insights into human evolution and disease. Nat Rev Genet 4, 20–28 (2003).

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