Human Transcriptome Evolution


It has been a long‐standing hypothesis that evolution of the human transcriptome (the collection of all gene transcripts in a cell) may have contributed greatly to the observed human‐specific phenotypes. With recent advances in high throughput technologies and bioinformatic tools, it becomes possible to get deep understandings of this important issue. Here, we provided a brief but updated summary of the exciting findings in the study of human transcriptome evolution.

Keywords: transcriptome; genomic analysis; human evolution

Figure 1.

(a) Distance trees representing the relative extent of expression changes in brain and liver among three primates: Human, Chimpanzee (Chimp.) and Orangutan (Orang.). (b) Ratio of human‐lineage‐specific expression changes to chimpanzee‐lineage‐specific expression changes (LH/LC) in both brain and liver under different significance levels (alpha=0.05, 0.02, 0.01 and 0.001).

Figure 2.

Induction/repression (I/R) ratios for genes showing lineage‐specific expression patterns. (a) In the human brain and liver. The I/R ratio of brain‐expressed genes is statistically greater than one, whereas the I/R ratio of liver‐expressed genes is not significant. (b) In the chimpanzee brain and liver. The I/R ratios for both brain‐ and liver‐expressed genes are relatively similar, and sensitive, to the significance level.

Figure 3.

(a) Schematic illustration of gene expression variation among and between humans and chimpanzees in five tissues. Brain shows the smallest divergence and diversity. (b) Variation of human–mouse tissue expression distances (Eti) among 29 tissues. Abbreviations for these tissues are shown in parentheses.

Figure 4.

Correlations between tissue expression distance (Eti) and tissue protein distance (Dti) for highly expressed proteins (a) and for normally expressed proteins (b). (c) The correlation between tissue expression distance (Eti) and tissue duplicate distances (Tdup). Here, Tdup is the average of human and mouse duplicates.



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

Blencowe BJ (2006) Alternative splicing: new insights from global analyses. Cell 126: 37–47.

Carroll SB (2003) Genetics and the making of Homo sapiens. Nature 422: 849–857.

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

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

Gilad Y, Oshlack A and Rifkin SA (2006a) Natural selection on gene expression. Trends in Genetics 22: 456–461.

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

Gu X (2004) Statistical framework for phylogenomic analysis of gene family expression profiles. Genetics 167: 531–542.

Gu J and Gu X (2003) Induced gene expression in human brain after the split from chimpanzee. Trends in Genetics 19: 63–65.

Gu X and Su Z (2007) Tissue‐driven hypothesis of genomic evolution and sequence‐expression correlations. Proceedings of the National Academy of Sciences of the USA 104: 2779–2784.

Guo H, Weiss RE, Gu X and Suchard MA (2007) Time squared: repeated measures on phylogenies. Molecular Biology and Evolution 24: 352–362.

Huminiecki L and Wolfe KH (2004) Divergence of spatial gene expression profiles following species‐specific gene duplications in human and mouse. Genome Research 14: 1870–1879.

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

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

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

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

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

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

Lemos B, Meiklejohn CD, Caceres M and Hartl DL (2005) Rates of divergence in gene expression profiles of primates, mice, and flies: stabilizing selection and variability among functional categories. Evolution; International Journal of Organic Evolution 59: 126–137.

Li WH, Yang J and Gu X (2005) Expression divergence between duplicate genes. Trends in Genetics 21: 602–607.

Makova KD and Li WH (2003) Divergence in the spatial pattern of gene expression between human duplicate genes. Genome Research 13: 1638–1645.

Oakley TH, Gu Z, Abouheif E, Patel NH and Li WH (2005) Comparative methods for the analysis of gene‐expression evolution: an example using yeast functional genomic data. Molecular Biology and Evolution 22: 40–50.

Rifkin SA, Kim J and White KP (2003) Evolution of gene expression in the Drosophila melanogaster subgroup. Nature Genetics 33: 138–144.

Su Z, Wang J, Yu J, Huang X and Gu X (2006) Evolution of alternative splicing after gene duplication. Genome Research 16: 182–189.

Xing Y and Lee C (2005) Evidence of functional selection pressure for alternative splicing events that accelerate evolution of protein subsequences. Proceedings of the National Academy of Sciences of the USA 102: 13526–13531.

Yanai I, Graur D and Ophir R (2004) Incongruent expression profiles between human and mouse orthologous genes suggest widespread neutral evolution of transcription control. Omics 8: 15–24.

Further Reading

Bar‐Or C, Czosnek H and Koltai H (2007) Cross‐species microarray hybridizations: a developing tool for studying species diversity. Trends in Genetics 23: 200–207.

Evans PD, Anderson JR, Vallender EJ et al. (2004) Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Human Molecular Genetics 13: 489–494.

Fay JC and Wittkopp PJ (2008) Evaluating the role of natural selection in the evolution of gene regulation. Heredity 100: 191–199.

Velculescu VE, Zhang L, Zhou W et al. (1997) Characterization of the yeast transcriptome. Cell 88: 243–251.

Web Links

NCBI Gene Expression Omnibus

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

* Required Field

How to Cite close
Gu, Xun, and Huang, Yong(Jul 2008) Human Transcriptome Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020772]