Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Evolution of primate gene expression

Key Points

  • Gene expression patterns differ substantially among even closely related primate species.

  • The extent of transcriptome divergence between species increases monotonically with evolutionary time since their divergence.

  • The extent of divergence of overall gene expression between species differs among tissues and, in a given tissue, parallels the extent of divergence of the amino-acid sequences of proteins expressed in that tissue.

  • A neutral theory of evolution, where divergence is primarily determined by negative selection and time since divergence, seems to be an adequate and useful null hypothesis for evolutionary analyses of the transcriptome.

  • Genes expressed in the testes have experienced positive selection both with respect to their expression and to their sequences among primates.

  • Gene expression in the brain has diverged less than that of other tissues analysed to date, but a tendency for acceleration of changes on the human lineage relative to the chimpanzee lineage could indicate positive selection.

Abstract

It has been suggested that evolutionary changes in gene expression account for most phenotypic differences between species, in particular between humans and apes. What general rules can be described governing expression evolution? We find that a neutral model where negative selection and divergence time are the major factors is a useful null hypothesis for both transcriptome and genome evolution. Two tissues that stand out with regard to gene expression are the testes, where positive selection has exerted a substantial influence in both humans and chimpanzees, and the brain, where gene expression has changed less than in other organs but acceleration might have occurred in human ancestors.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Expression divergence between humans and chimpanzees in different tissues.
Figure 2: Negative selection adds up across tissues.
Figure 3: Hierarchical clustering of expression differences between humans and chimpanzees in five different tissues.

References

  1. King, M. C. & Wilson, A. C. Evolution at two levels in humans and chimpanzees. Science 188, 107–116 (1975).

    Article  CAS  PubMed  Google Scholar 

  2. Szathmary, E. & Smith, J. M. The major evolutionary transitions. Nature 374, 227–232 (1995).

    Article  CAS  PubMed  Google Scholar 

  3. Breuer, T., Ndoundou-Hockemba, M. & Fishlock, V. First observation of tool use in wild gorillas. PLoS Biol. 3, e380 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Galdikas, B. M. Orangutan tool use. Science 243, 152 (1989).

    Article  CAS  PubMed  Google Scholar 

  5. Boesch, C. & Boesch, H. Tool use and tool making in wild chimpanzees. Folia Primatol. (Basel) 54, 86–99 (1990).

    Article  CAS  Google Scholar 

  6. Sugiyama, Y. Tool use by wild chimpanzees. Nature 367, 327 (1994).

    Article  CAS  PubMed  Google Scholar 

  7. Phillips, K. A. Tool use in wild capuchin monkeys (Cebus albifrons trinitatis). Am. J. Primatol. 46, 259–261 (1998).

    Article  CAS  PubMed  Google Scholar 

  8. Ducoing, A. M. & Thierry, B. Tool-use learning in Tonkean macaques (Macaca tonkeana). Anim. Cogn. 8, 103–113 (2005).

    Article  PubMed  Google Scholar 

  9. Whiten, A. et al. Cultures in chimpanzees. Nature 399, 682–685 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. van Schaik, C. P. et al. Orangutan cultures and the evolution of material culture. Science 299, 102–105 (2003).

    Article  CAS  PubMed  Google Scholar 

  11. Avital, E. & Jablonka, E. Animal Traditions: Behavioural Inheritance in Evolution (Cambridge Univ. Press, Cambridge; New York, 2000).

    Book  Google Scholar 

  12. Whiten, A. The second inheritance system of chimpanzees and humans. Nature 437, 52–55 (2005).

    Article  CAS  PubMed  Google Scholar 

  13. Glazko, G. V. & Nei, M. Estimation of divergence times for major lineages of primate species. Mol. Biol. Evol. 20, 424–434 (2003).

    Article  CAS  PubMed  Google Scholar 

  14. Mikkelsen, T. et al. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2005). This paper discusses human and chimpanzee evolution on the level of genomic DNA sequence.

    Article  CAS  Google Scholar 

  15. Wienberg, J. Fluorescence in situ hybridization to chromosomes as a tool to understand human and primate genome evolution. Cytogenet. Genome Res. 108, 139–160 (2005).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  17. Varki, A. & Altheide, T. K. Comparing the human and chimpanzee genomes: searching for needles in a haystack. Genome Res. 15, 1746–1758 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. Gilbert, S. L., Dobyns, W. B. & Lahn, B. T. Genetic links between brain development and brain evolution. Nature Rev. Genet. 6, 581–590 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. Khaitovich, P. et al. A neutral model of transcriptome evolution. PLoS Biol. 2, e132 (2004). This paper summarizes how the neutral theory can be applied to gene expression evolution.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Preuss, T. M., Caceres, M., Oldham, M. C. & Geschwind, D. H. Human brain evolution: insights from microarrays. Nature Rev. Genet. 5, 850–860 (2004).

    Article  CAS  PubMed  Google Scholar 

  21. Gilad, Y., Rifkin, S. A., Bertone, P., Gerstein, M. & White, K. P. Multi-species microarrays reveal the effect of sequence divergence on gene expression profiles. Genome Res. 15, 674–680 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Whitehead, A. & Crawford, D. L. Variation within and among species in gene expression: raw material for evolution. Mol. Ecol. 15, 1197–1211 (2006).

    Article  CAS  PubMed  Google Scholar 

  23. Ranz, J. M. & Machado, C. A. Uncovering evolutionary patterns of gene expression using microarrays. Trends Ecol. Evol. 21, 29–37 (2006).

    Article  PubMed  Google Scholar 

  24. Rifkin, S. A., Kim, J. & White, K. P. Evolution of gene expression in the Drosophila melanogaster subgroup. Nature Genet. 33, 138–144 (2003). This paper describes the expression evolution in Drosophila melanogaster and demonstrates that expression differences correlate with divergence time as measured from DNA sequences.

    Article  CAS  PubMed  Google Scholar 

  25. Nuzhdin, S. V., Wayne, M. L., Harmon, K. L. & McIntyre, L. M. Common pattern of evolution of gene expression level and protein sequence in Drosophila. Mol. Biol. Evol. 21, 1308–1317 (2004). This paper argues that positive selection is a substantial factor in expression evolution in Drosophila.

    Article  CAS  PubMed  Google Scholar 

  26. Lemos, B., Meiklejohn, C. D., Caceres, M. & Hartl, D. L. Rates of divergence in gene expression profiles of primates, mice, and flies: stabilizing selection and variability among functional categories. Evolution Int. J. Org. Evolution 59, 126–137 (2005).

    Article  CAS  Google Scholar 

  27. Denver, D. R. et al. The transcriptional consequences of mutation and natural selection in Caenorhabditis elegans. Nature Genet. 37, 544–548 (2005). This paper shows that negative selection has a dominant role in gene expression evolution in Caenorhabditis elegans.

    Article  CAS  PubMed  Google Scholar 

  28. Rifkin, S. A., Houle, D., Kim, J. & White, K. P. A mutation accumulation assay reveals a broad capacity for rapid evolution of gene expression. Nature 438, 220–223 (2005). This paper shows that negative selection has a dominant role in gene expression evolution in Drosophila.

    Article  CAS  PubMed  Google Scholar 

  29. Khaitovich, P. et al. Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science 309, 1850–1854 (2005). This paper demonstrates that modes of protein sequences and gene expression evolution are similar to one another, but differ among tissues in primates.

    Article  CAS  PubMed  Google Scholar 

  30. Gilad, Y., Oshlack, A., Smyth, G. K., Speed, T. P. & White, K. P. Expression profiling in primates reveals a rapid evolution of human transcription factors. Nature 440, 242–245 (2006).

    Article  CAS  PubMed  Google Scholar 

  31. Jordan, I. K., Marino-Ramirez, L., Wolf, Y. I. & Koonin, E. V. Conservation and coevolution in the scale-free human gene coexpression network. Mol. Biol. Evol. 21, 2058–2070 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  33. Liao, B. Y. & Zhang, J. Evolutionary conservation of expression profiles between human and mouse orthologous genes. Mol. Biol. Evol. 23, 530–540 (2006).

    Article  CAS  PubMed  Google Scholar 

  34. Korneev, S. A., Park, J. H. & O'Shea, M. Neuronal expression of neural nitric oxide synthase (nNOS) protein is suppressed by an antisense RNA transcribed from an NOS pseudogene. J. Neurosci. 19, 7711–7720 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hirotsune, S. et al. An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Nature 423, 91–96 (2003).

    Article  CAS  PubMed  Google Scholar 

  36. Fay, J. C., McCullough, H. L., Sniegowski, P. D. & Eisen, M. B. Population genetic variation in gene expression is associated with phenotypic variation in Saccharomyces cerevisiae. Genome Biol. 5, R26 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Whitehead, A. & Crawford, D. L. Neutral and adaptive variation in gene expression. Proc. Natl Acad. Sci. USA 103, 5425–5430 (2006). This paper uses expression variation within and between populations to assess influence of positive and negative selection on expression evolution in teleost fish.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jordan, I. K., Marino-Ramirez, L. & Koonin, E. V. Evolutionary significance of gene expression divergence. Gene 345, 119–126 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Oleksiak, M. F., Churchill, G. A. & Crawford, D. L. Variation in gene expression within and among natural populations. Nature Genet. 32, 261–266 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Khaitovich, P. et al. Regional patterns of gene expression in human and chimpanzee brains. Genome Res. 14, 1462–1473 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fraser, H. B., Hirsh, A. E., Steinmetz, L. M., Sharfe, C. & Feldman, M. W. Evolutionary rate in the protein interaction network. Science 296, 750–752 (2002).

    Article  CAS  PubMed  Google Scholar 

  42. Lemos, B., Bettencourt, B. R., Meiklejohn, C. D. & Hartl, D. L. Evolution of proteins and gene expression levels are coupled in Drosophila and are independently associated with mRNA abundance, protein length, and number of protein–protein interactions. Mol. Biol. Evol. 22, 1345–1354 (2005). This paper demonstrates that modes of protein sequences and gene expression evolution are similar in Drosophila.

    Article  CAS  PubMed  Google Scholar 

  43. Smith, N. G. & Eyre-Walker, A. Adaptive protein evolution in Drosophila. Nature 415, 1022–1024 (2002).

    Article  CAS  PubMed  Google Scholar 

  44. Fay, J. C., Wyckoff, G. J. & Wu, C. I. Testing the neutral theory of molecular evolution with genomic data from Drosophila. Nature 415, 1024–1026 (2002).

    Article  CAS  PubMed  Google Scholar 

  45. Lynch, M. & Hill, W. G. Phenotypic evolution by neutral mutation. Evolution 40, 915–935 (1986).

    Article  PubMed  Google Scholar 

  46. Rice, W. R. Sex chromosomes and the evolution of sexual dimorphism. Evolution 38, 735–742 (1984).

    Article  PubMed  Google Scholar 

  47. Nielsen, R. et al. A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol. 3, e170 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Wyckoff, G. J., Wang, W. & Wu, C. I. Rapid evolution of male reproductive genes in the descent of man. Nature 403, 304–309 (2000).

    Article  CAS  PubMed  Google Scholar 

  49. Voight, B. F., Kudaravalli, S., Wen, X. & Pritchard, J. K. A map of recent positive selection in the human genome. PLoS Biol. 4, e72 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Clark, N. L. & Swanson, W. J. Pervasive adaptive evolution in primate seminal proteins. PLoS Genet. 1, e35 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Swanson, W. J. & Vacquier, V. D. The rapid evolution of reproductive proteins. Nature Rev. Genet. 3, 137–144 (2002).

    Article  CAS  PubMed  Google Scholar 

  52. Good, J. M. & Nachman, M. W. Rates of protein evolution are positively correlated with developmental timing of expression during mouse spermatogenesis. Mol. Biol. Evol. 22, 1044–1052 (2005).

    Article  CAS  PubMed  Google Scholar 

  53. Meiklejohn, C. D., Parsch, J., Ranz, J. M. & Hartl, D. L. Rapid evolution of male-biased gene expression in Drosophila. Proc. Natl Acad. Sci. USA 100, 9894–9899 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ranz, J. M., Castillo-Davis, C. I., Meiklejohn, C. D. & Hartl, D. L. Sex-dependent gene expression and evolution of the Drosophila transcriptome. Science 300, 1742–1745 (2003).

    Article  CAS  PubMed  Google Scholar 

  55. Zhang, Z. & Parsch, J. Positive correlation between evolutionary rate and recombination rate in Drosophila genes with male-biased expression. Mol. Biol. Evol. 22, 1945–1947 (2005).

    Article  CAS  PubMed  Google Scholar 

  56. Zhang, Z., Hambuch, T. M. & Parsch, J. Molecular evolution of sex-biased genes in Drosophila. Mol. Biol. Evol. 21, 2130–2139 (2004).

    Article  CAS  PubMed  Google Scholar 

  57. Lindblad-Toh, K. et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438, 803–819 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Goriely, A. et al. Gain-of-function amino acid substitutions drive positive selection of FGFR2 mutations in human spermatogonia. Proc. Natl Acad. Sci. USA 102, 6051–6056 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kleene, K. C. A possible meiotic function of the peculiar patterns of gene expression in mammalian spermatogenic cells. Mech. Dev. 106, 3–23 (2001).

    Article  CAS  PubMed  Google Scholar 

  60. Kleene, K. C. Patterns, mechanisms, and functions of translation regulation in mammalian spermatogenic cells. Cytogenet. Genome Res. 103, 217–224 (2003).

    Article  CAS  PubMed  Google Scholar 

  61. Birkhead, T. R. & Pizzari, T. Postcopulatory sexual selection. Nature Rev. Genet. 3, 262–273 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. Robbins, M. M. et al. Social structure and life-history patterns in western gorillas (Gorilla gorilla gorilla). Am. J. Primatol. 64, 145–159 (2004).

    Article  PubMed  Google Scholar 

  63. Lyttle, T. W. Cheaters sometimes prosper: distortion of mendelian segregation by meiotic drive. Trends Genet. 9, 205–210 (1993).

    Article  CAS  PubMed  Google Scholar 

  64. Parker, G. A. & Begon, M. E. Sperm competition games: sperm size and number under gametic control. Proc. Biol. Sci. 253, 255–262 (1993).

    Article  CAS  PubMed  Google Scholar 

  65. Parker, G. A. Sperm competition games: sperm size and sperm number under adult control. Proc. Biol. Sci. 253, 245–254 (1993).

    Article  CAS  PubMed  Google Scholar 

  66. Haig, D. & Bergstrom, C. T. Multiple mating, sperm competition and meiotic drive. J. Evol. Biol. 8, 265–282 (1995).

    Article  Google Scholar 

  67. Handel, M. Spermatogenesis: Genetic Aspects Vol. 15 (ed. Hennig, W.) (Springer, Berlin, 1987).

    Google Scholar 

  68. Kierszenbaum, A. & Tres, L. L. Structural and transcriptional features of mouse spermatid genome. J. Cell Biol. 65, 258–270 (1975).

    Article  CAS  PubMed  Google Scholar 

  69. Kouprina, N. et al. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion. PLoS Biol. 2, e126 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Evans, P. D. et al. Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans. Science 309, 1717–1720 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Kouprina, N. et al. The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein. Hum. Mol. Genet. 14, 2155–2165 (2005).

    Article  CAS  PubMed  Google Scholar 

  72. Enard, W. et al. Intra- and interspecific variation in primate gene expression patterns. Science 296, 340–343 (2002). The first paper that compared gene expression patterns in primates and described a brain-specific acceleration in humans.

    Article  CAS  PubMed  Google Scholar 

  73. Caceres, M. et al. Elevated gene expression levels distinguish human from non-human primate brains. Proc. Natl Acad. Sci. USA 100, 13030–13035 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gu, J. & Gu, X. Induced gene expression in human brain after the split from chimpanzee. Trends Genet. 19, 63–65 (2003).

    Article  CAS  PubMed  Google Scholar 

  75. Hsieh, W. P., Chu, T. M., Wolfinger, R. D. & Gibson, G. Mixed-model reanalysis of primate data suggests tissue and species biases in oligonucleotide-based gene expression profiles. Genetics 165, 747–757 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Dorus, S. et al. Accelerated evolution of nervous system genes in the origin of Homo sapiens. Cell 119, 1027–1040 (2004).

    Article  CAS  PubMed  Google Scholar 

  78. Khaitovich, P. et al. Positive selection on gene expression in the human brain. Curr. Biol. 16, R356–R358 (2006).

    Article  CAS  PubMed  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  80. Ohyama, H. et al. Laser capture microdissection-generated target sample for high-density oligonucleotide array hybridization. Biotechniques 29, 530–536 (2000).

    Article  CAS  PubMed  Google Scholar 

  81. Mikulowska-Mennis, A. et al. High-quality RNA from cells isolated by laser capture microdissection. Biotechniques 33, 176–179 (2002).

    Article  CAS  PubMed  Google Scholar 

  82. Yanai, I. et al. Similar gene expression profiles do not imply similar tissue functions. Trends Genet. 22, 132–138 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Gibson, G. & Weir, B. The quantitative genetics of transcription. Trends Genet. 21, 616–623 (2005).

    Article  CAS  PubMed  Google Scholar 

  84. Su, A. I. et al. Large-scale analysis of the human and mouse transcriptomes. Proc. Natl Acad. Sci. USA 99, 4465–4470 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Su, A. I. et al. A gene atlas of the mouse and human protein-encoding transcriptomes. Proc. Natl Acad. Sci. USA 101, 6062–6067 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Altshuler, D. et al. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).

    Article  CAS  Google Scholar 

  87. Lewontin, R. C. & Hubby, J. L. A molecular approach to the study of genic heterozygosity in natural populations. II. Amount of variation and degree of heterozygosity in natural populations of Drosophila pseudoobscura. Genetics 54, 595–609 (1966).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Darwin, C. The Origin of Species by Means of Natural Selection; or, the Preservation of Favored Races in the Struggle for Life (John Murray, London, 1859).

    Google Scholar 

  89. Kimura, M. Natural selection as the process of accumulating genetic information in adaptive evolution. Genet. Res. 2, 127–140 (1961).

    Article  Google Scholar 

  90. Kimura, M. The Neutral Theory of Molecular Evolution (Cambridge Univ. Press, Cambridge, New York, 1983).

    Book  Google Scholar 

  91. Ohta, T. Slightly deleterious mutant substitutions in evolution. Nature 246, 96–98 (1973).

    Article  CAS  PubMed  Google Scholar 

  92. Ohta, T. Near-neutrality in evolution of genes and gene regulation. Proc. Natl Acad. Sci. USA 99, 16134–16137 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Hudson, R. R., Kreitman, M. & Aguade, M. A test of neutral molecular evolution based on nucleotide data. Genetics 116, 153–9 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. McDonald, J. H. & Kreitman, M. Adaptive protein evolution at the Adh locus in Drosophila. Nature 351, 652–654 (1991).

    Article  CAS  PubMed  Google Scholar 

  95. Tajima, F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123, 585–595 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Fu, Y. X. & Li, W. H. Statistical tests of neutrality of mutations. Genetics 133, 693–709 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Fay, J. C. & Wu, C. I. Sequence divergence, functional constraint, and selection in protein evolution. Annu. Rev. Genomics Hum. Genet. 4, 213–235 (2003).

    Article  CAS  PubMed  Google Scholar 

  98. Tomita, H. et al. Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain. Biol. Psychiatry 55, 346–352 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Li, J. Z. et al. Systematic changes in gene expression in postmortem human brains associated with tissue pH and terminal medical conditions. Hum. Mol. Genet. 13, 609–616 (2004).

    Article  CAS  PubMed  Google Scholar 

  100. Franz, H. et al. Systematic analysis of gene expression in human brains before and after death. Genome Biol. 6, R112 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Marvanova, M. et al. Microarray analysis of nonhuman primates: validation of experimental models in neurological disorders. FASEB J. 17, 929–931 (2003).

    Article  CAS  PubMed  Google Scholar 

  102. Uddin, M. et al. Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain gene expression profiles. Proc. Natl Acad. Sci. USA 101, 2957–2962 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Margulies, M. et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437, 376–380 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Whitehead, A. & Crawford, D. L. Variation in tissue-specific gene expression among natural populations. Genome Biol. 6, R13 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Pal, C., Papp, B. & Lercher, M. J. An integrated view of protein evolution. Nature Rev. Genet. 7, 337–348 (2006).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank R.E. Green and S.E. Ptak for many helpful comments on the manuscript and all members of our group for fruitful discussions. The research on primate gene expression in our laboratory is supported by the Max Planck Society and the Bundesministerium für Bildung und Forschung.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Svante Pääbo.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

International HapMap project

Glossary

Negative selection

Removal of genetic variants in a population that decrease the fitness of their carrier. If negative selection acts on a phenotypic trait, this is also called stabilizing selection.

Positive selection

Increase in frequency of a genetic variant or a phenotypic trait because it increases the fitness of its carrier. If positive selection acts on a phenotypic trait, this is also called directional selection.

Sperm competition

The direct competition between sperm from different males that occurs when females copulate with multiple males.

Meiotic drive

Preferential transmission of one of two alleles from a parent to its offspring.

Outgroups

Species that are more distantly related to two or more species studied and can therefore be used to estimate the ancestral state of a trait such as nucleotide sequence or gene expression level.

Linkage disequilibrium

Non-random association of nucleotide polymorphisms along the chromosome. Larger areas of stronger linkage disequilibrium are seen around a genetic change that has been positively selected in the recent past.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Khaitovich, P., Enard, W., Lachmann, M. et al. Evolution of primate gene expression. Nat Rev Genet 7, 693–702 (2006). https://doi.org/10.1038/nrg1940

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg1940

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing