Human and Chimpanzee Transcriptomes: Comparative Evolution


The biological basis of the uniqueness of human abilities is one of the most fascinating research topics of all time. Evolutionary studies now allow us, at least in principle, to identify the underlying functional genetic elements which are specific to humans. However, despite enormous progress in the biosciences over recent years, which has resulted in the complete sequencing of the human genome as well as the genomes of two closely related primate species – chimpanzee and rhesus macaque – the molecular mechanisms underlying human‐specific abilities remain unknown. Gene expression studies now provide us with a powerful tool to identify the functional differences distinguishing humans from chimpanzees, our closest living relatives. From the evolutionary and functional perspective, however, the interpretation of the observed expression differences is almost never as straightforward as we would ideally like.

Keywords: microarrays; human; chimpanzee; brain; expression

Figure 1.

Hierarchical clustering of expression differences between humans and chimpanzees in five different tissues. All probe sets differently expressed between humans and chimpanzees in at least one tissue are shown. Genes in red are more highly expressed in humans than in chimpanzees, whereas genes in blue represent the reverse. It is noteworthy that the testes exhibit many more differences than the other four tissues. Reproduced from Khaitovich et al..

Figure 2.

Gene expression differences between humans and chimpanzees according to Khaitovich et al.. (a) Hierarchical clustering of expression differences between humans and chimpanzees in the prefrontal cortex with (PFC) and without (PFC N) masking of the sequence differences between the species and previously published prefrontal cortex (PFC') and liver data (Enard et al., ). All genes differentially expressed in at least one tissue and detected in the other are shown. The vertical black bar indicates the cluster of expression differences that disappears after the masking procedure. (b) Hierarchical clustering of genes classified as differentially expressed between humans and chimpanzees in at least one out of six studied brain regions. Each row represents a gene and each column represents a pairwise comparison between one human and one chimpanzee in a given tissue. The magnitude of the expression differences is shown as the base two logarithm of the ratio of the gene expression level in humans to that in chimpanzees. Higher expression in humans is shown in red and higher expression in chimpanzees in blue, with colour intensity being proportional to the magnitude of the expression difference as indicated by the colour bar at the bottom of the figure. B, Broca's area; PFC, prefrontal cortex; PVC, primary visual cortex; ACC, anterior cingulate cortex; CN, caudate nucleus and CB, cerebellum. Reproduced with permission from Khaitovich et al..

Figure 3.

Indication of positive selection on brain gene expression in humans. The correlation between expression divergence in the human lineage and size of linkage disequilibrium (LD) regions in (a) four different tissues (red: brain; blue: heart; black: kidney; grey: liver); (b) for brain in three human populations (red: Chinese; blue: Europeans; black: Africans); (c) for brain corrected for recombination rate variation across the genome (dark red: LD size with no correction; red: LD size corrected for the recombination rate by partial correlation; dark blue: direct correlation between recombination rate and expression divergence on the human lineage); (d) for brain corrected for recombination rate variation across the genome using independent data for 10 humans, one chimpanzee and six macaques (symbols as in (c)). Expression divergence cutoffs are shown as quantiles of the divergence distribution for all genes expressed in a given tissue. Thus, the 0.8 quantile cutoff corresponds to 20% of all expressed genes with the largest expression divergence between humans and chimpanzees in a given tissue. Points represent Spearman rank correlation coefficients for single human populations (b, all measures; c and d, recombination rate measures) or an average of three human populations. The filled circles indicate significant correlations for all included populations at the 1% level. CR: correlation coefficient. Reproduced with permission from Khaitovich et al..



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Khaitovich, Philipp, Kehrer‐Sawatzki, Hildegard, and Cooper, David N(Jul 2008) Human and Chimpanzee Transcriptomes: Comparative Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020770]