Human and Chimpanzee Transcriptomes: Comparative Evolution

Abstract

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..

close

References

Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116: 281–297.

Berezikov E, Thuemmler F, van Laake LW et al. (2006) Diversity of microRNAs in human and chimpanzee brain. Nature Genetics 38: 1375–1377.

Brenner S, Johnson M, Bridgham J et al. (2000) Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arrays. Nature Biotechnology 18: 630–634.

Britten RJ (2002) Divergence between samples of chimpanzee and human DNA sequences is 5%, counting indels. Proceedings of the National Academy of Sciences of the USA 99: 13633–13635.

Cáceres M, Lachuer J, Zapala MA et al. (2003) Elevated gene expression levels distinguish human from non‐human primate brains. Proceedings of the National Academy of Sciences of the USA 100: 13030–13035.

Cheng J, Kapranov P, Drenkow J et al. (2005) Transcriptional maps of 10 human chromosomes at 5‐nucleotide resolution. Science 308: 1149–1154.

Chimpanzee Sequencing and Analysis Consortium (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437: 69–87.

Coqueugniot H, Hublin JJ, Veillon F, Houët F and Jacob T (2004) Early brain growth in Homo erectus and implications for cognitive ability. Nature 431: 299–302.

Darwin C (1859) The Origin of Species by Means of Natural Selection. London: John Murray.

DeSilva J and Lesnik J (2006) Chimpanzee neonatal brain size: implications for brain growth in Homo erectus. Journal of Human Evolution 51: 207–212.

Enard W, Khaitovich P, Klose J et al. (2002a) Intra‐ and interspecific variation in primate gene expression patterns. Science 296: 340–343.

Enard W, Przeworski M, Fisher SE et al. (2002b) Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418: 869–872.

Evans PD, Gilbert SL, Mekel‐Bobrov N et al. (2005) Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans. Science 309: 1717–1720.

Fu N, Drinnenberg I, Kelso J et al. (2007) Comparison of protein and mRNA expression evolution in humans and chimpanzees. PLoS ONE 2: e216.

Glazko GV and Nei M (2003) Estimation of divergence times for major lineages of primate species. Molecular Biology and Evolution 20: 424–434.

Grossman LI, Wildman DE, Schmidt TR and Goodman M (2004) Accelerated evolution of the electron transport chain in anthropoid primates. Trends in Genetics 20: 578–585.

Haygood R, Fedrigo O, Hanson B, Yokoyama KD and Wray GA (2007) Promoter regions of many neural‐ and nutrition‐related genes have experienced positive selection during human evolution. Nature Genetics 39: 1140–1144.

Imanishi T, Itoh T, Suzuki Y et al. (2004) Integrative annotation of 21 037 human genes validated by full‐length cDNA clones. PLoS Biology 2: e162.

International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437: 1299–1320.

Kapranov P, Cawley SE, Drenkow J et al. (2002) Large‐scale transcriptional activity in chromosomes 21 and 22. Science 296: 916–919.

Khaitovich P, Hellmann I, Enard W et al. (2005) Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science 309: 1850–1854.

Khaitovich P, Tang K, Franz H et al. (2006) Positive selection on gene expression in the human brain. Current Biology 16: R356–R358.

Khaitovich P, Weiss G, Lachmann M et al. (2004) A neutral model of transcriptome evolution. PLoS Biology 2: E132.

Kimura M (1968) Evolutionary rate at the molecular level. Nature 217: 624–626.

Kimura M (1983) The Neutral Theory of Molecular Evolution. Cambridge: Cambridge University Press.

King MC and Wilson AC (1975) Evolution at two levels in humans and chimpanzees. Science 188: 107–116.

Kumar S, Filipski A, Swarna V, Walker A and Hedges SB (2005) Placing confidence limits on the molecular age of the human–chimpanzee divergence. Proceedings of the National Academy of Sciences of the USA 102: 18842–18847.

Lockhart DJ and Barlow C (2001) Expressing what's on your mind: DNA arrays and the brain. Nature Reviews. Neuroscience 2: 63–68.

Mekel‐Bobrov N, Gilbert SL, Evans PD et al. (2005) Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens. Science 309: 1720–1722.

Mink JW, Blumenschine RJ and Adams DB (1981) Ratio of central nervous system to body metabolism in vertebrates: its constancy and functional basis. American Journal of Physiology 241: R203–R212.

Przeworski M (2002) The signature of positive selection at randomly chosen loci. Genetics 160: 1179–1189.

Rhesus Macaque Genome Sequencing and Analysis Consortium, Gibbs RA, Rogers J et al. (2007) Evolutionary and biomedical insights from the rhesus macaque genome. Science 316: 222–234.

Sabeti PC, Reich DE, Higgins JM et al. (2002) Detecting recent positive selection in the human genome from haplotype structure. Nature 419: 832–837.

Sheng QH, Wang LS, Dai J et al. (2006) Comparison of a proteomic approach with a microarray‐based approach to detect exons in the mouse genome. Nature Genetics 38: 1223–1224.

Varki A and Altheide TK (2005) Comparing the human and chimpanzee genomes: searching for needles in a haystack. Genome Research 15: 1746–1758.

Wang HY, Chien HC, Osada N et al. (2007) Rate of evolution in brain‐expressed genes in humans and other primates. PLoS Biology 5: e13.

Further Reading

Fisher SE and Marcus GF (2006) The eloquent ape: genes, brains and the evolution of language. Nature Reviews. Genetics 7: 9–20.

Gilad Y, Oshlack A, Smyth GK, Speed TP and White KP (2006) Expression profiling in primates reveals a rapid evolution of human transcription factors. Nature 440: 242–245.

Gilad Y, Rifkin SA, Bertone P, Gerstein M and White KP (2005) Multi‐species microarrays reveal the effect of sequence divergence on gene expression profiles. Genome Research 15: 674–680.

Khaitovich P, Enard W, Lachmann M and Pääbo S (2006) Evolution of primate gene expression. Nature Reviews. Genetics 7(9): 693–702.

Khaitovich P, Kelso J, Franz H et al. (2006) Functionality of intergenic transcription: an evolutionary comparison. PLoS Genetics 2: e171.

Khaitovich P, Muetzel B, She X et al. (2004) Regional patterns of gene expression in human and chimpanzee brains. Genome Research 14: 1462–1473.

Khaitovich P, Pääbo S and Weiss G (2005) Toward a neutral evolutionary model of gene expression. Genetics 170: 929–939.

Marquès‐Bonet T, Cáceres M, Bertranpetit J et al. (2004) Chromosomal rearrangements and the genomic distribution of gene‐expression divergence in humans and chimpanzees. Trends in Genetics 20: 524–529.

Oldham MC, Horvath S and Geschwind DH (2006) Conservation and evolution of gene coexpression networks in human and chimpanzee brains. Proceedings of the National Academy of Sciences of the USA 103: 17973–17978.

Uddin M, Wildman DE, Liu G et al. (2004) Sister grouping of chimpanzees and humans as revealed by genome‐wide phylogenetic analysis of brain gene expression profiles. Proceedings of the National Academy of Sciences of the USA 101: 2957–2962.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

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