Intra- and Interspecific Variation in Primate Gene Expression Patterns

Summary of article appearing in Science, Vol 296, 12 April 2002, pp. 340-343.

Article by:William Enard, Philipp Khaitovich, Joachim Klose, Sebastian Zollner, Florian Heissig, Patrick Giavalisco, Kay Nieselt-Stuwe, Elaine Muchmore, Ajit Varki, Rivka Ravid, Gaby M. Doxiadis, Ronal E. Bontrop and Svante Paabo.

Humans and chimpanzees share 98.7% of their DNA sequences yet are very different in morphology, behavior and cognitive abilities. According to this paper, these distinctions result not from differences in the protein products produced by the DNA, but in the ways in which the genes are expressed. Gene expression changes can occur when genes are deleted or duplicated, or when levels of transcription factors change.

This study compares the gene expression patterns in humans, chimpanzees, orangutans and rhesus macaques. Another comparison was made between species of mice that have been evolving as separate lineages for as long as apes and humans have been split. The authors compared levels of mRNA to measure the amount of transcription from DNA in the liver, brain and blood. Protein patterns were also compared in the brains of these species.

The study found high levels of intraspecific variation in gene expression. They showed that the amount of variation between individuals of the same species was high compared with the amount of variation between chimpanzees and humans.

When comparing interspecific differences, the transcriptomes of the blood and liver of chimpanzees and humans were more similar to each other than to those of the rhesus macaque, which is expected due to the close relationship between humans and chimpanzees. However, a different pattern was discovered in the expression patterns of the brain, with chimpanzees showing greater similarity to macaques than to humans. The human brain had a rate of change of gene expression levels that was 5.5 times faster compared to the other lineages. No evidence of accelerated evolutionary change was found in the blood or the liver.

Three mouse species were used to determine whether this pattern is unique to the primate lineage and whether the change in gene expression levels was unique to the human brain. They found that the rates of evolutionary change in gene expression for the mice were similar in the brain and liver. The evidence from the mice confirms that closely related mammalian species may still have very different gene expression patterns. Also, human brain evolution may have involved substantial evolutionary changes in gene expression levels at both the mRNA and the protein levels. Future work will examine how the differences in the patterns of gene expression relate to specific functional differences between the species.

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