Review Article | Published:

Human brain evolution: transcripts, metabolites and their regulators

Nature Reviews Neuroscience volume 14, pages 112127 (2013) | Download Citation

Abstract

What evolutionary events led to the emergence of human cognition? Although the genetic differences separating modern humans from both non-human primates (for example, chimpanzees) and archaic hominins (Neanderthals and Denisovans) are known, linking human-specific mutations to the cognitive phenotype remains a challenge. One strategy is to focus on human-specific changes at the level of intermediate phenotypes, such as gene expression and metabolism, in conjunction with evolutionary changes in gene regulation involving transcription factors, microRNA and proximal regulatory elements. In this Review we show how this strategy has yielded some of the first hints about the mechanisms of human cognition.

Key points

  • Studies investigating species-specific molecular phenotypes, such as gene expression or metabolome concentrations, can link genetic and phenotypic differences among species.

  • Human brain evolution may be divided into an early phase that is shared among Homo species and included a gradual increase in cranial volume and possibly increased communication skills, and a recent and rapid evolutionary phase that is possibly specific to the Homo sapiens species. This recent phase is characterized by a remodelling of brain development that enhanced human infant abilities for social learning.

  • Studies investigating human-specific changes that occur during postnatal brain development and that accompany human cognitive phenotype formation may provide more insights into the molecular mechanisms of human cognitive evolution than studies investigating human-specific features in adults only.

  • One recent insight emerging from comparative developmental studies is that the extended period of human cortical synaptogenesis that had been identified using synaptic density measurements in higher-order associative brain areas (such as the prefrontal cortex in the human–macaque comparison) is specific to humans. The pace of cortical synaptogenesis in chimpanzee brains is more similar to that of macaques than of humans.

  • Differences in the rates of cortical synaptogenesis between the prefrontal cortex of humans and non-human primates can be observed at the gene expression and metabolite concentration levels and might be driven by one or several mutations affecting a few transcriptional or epigenetic regulators. These mutations might have occurred after the separation of the human and the Neanderthal lineages 400,000 years ago.

  • Population genetics analyses show that the total number of genetic mutations underlying human brain evolution after the separation of the human and the Neanderthal lineages is likely to be small, possibly less than a dozen.

  • Many more human-specific changes that are as yet unknown might be revealed by studies that integrate different levels of biological data — epigenome, transcriptome, proteome and metabolome — from specific brain structures, separate cortical layers and individual cell types. Although rapid technological developments have provided us with the tools to conduct such studies, the low availability of well-characterized, good-quality brain samples, especially from non-human primates, remains the major stumbling block to future research efforts.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    The Cultural Origins of Human Cognition (Harvard Univ. Press, 1999).

  2. 2.

    & Not By Genes Alone: How Culture Transformed Human Evolution (Univ. of Chicago Press, 2004).

  3. 3.

    & The Origin and Evolution of Cultures (Oxford Univ. Press, 2005).

  4. 4.

    , & The emergence of human uniqueness: characters underlying behavioral modernity. Evol. Anthropol. 18, 187–200 (2009).

  5. 5.

    & The human socio-cognitive niche and its evolutionary origins. Phil. Trans. R. Soc. B 367, 2119–2129 (2012).

  6. 6.

    , & Ratcheting up the ratchet: on the evolution of cumulative culture. Phil. Trans. R. Soc. B. 364, 2405–2415 (2009).

  7. 7.

    & Evolution of the brain and intelligence in primates. Prog. Brain Res. 195, 413–430 (2012).

  8. 8.

    The human brain: rewired and running hot. Ann. NY Acad. Sci. 1225 (Suppl. 1), E182–E191 (2011). A comprehensive review of the current issues of debate in human brain evolution, including questions on the uniqueness of frontal cortex expansion in humans, human brain lateralization and connectivity.

  9. 9.

    Human brain evolution: from gene discovery to phenotype discovery. Proc. Natl Acad. Sci. USA 109 (Suppl. 1), 10709–10716 (2012).

  10. 10.

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

  11. 11.

    & Ape gestures and language evolution. Proc. Natl Acad. Sci. USA 104, 8184–8189 (2007).

  12. 12.

    & Savanna chimpanzees, Pan troglodytes verus, hunt with tools. Curr. Biol. 17, 412–417 (2007).

  13. 13.

    & Does the chimpanzee have a theory of mind? 30 years later. Trends Cogn. Sci. 12, 187–192 (2008).

  14. 14.

    & Bonobos voluntarily share their own food with others. Curr. Biol. 20, R230–R231 (2010).

  15. 15.

    , , & Spontaneous prosocial choice by chimpanzees. Proc. Natl Acad. Sci. USA 108, 13847–13851 (2011).

  16. 16.

    , , & Emulation, imitation, over-imitation and the scope of culture for child and chimpanzee. Phil. Trans. R. Soc. B 364, 2417–2428 (2009).

  17. 17.

    , & Evidence for cultural differences between neighboring chimpanzee communities. Curr. Biol. 22, 922–926 (2012).

  18. 18.

    What makes us human (Homo sapiens)? The challenge of cognitive cross-species comparison. J. Comp. Psychol. 121, 227–240 (2007).

  19. 19.

    & Evolution of the brain and intelligence. Trends Cogn. Sci. 9, 250–257 (2005).

  20. 20.

    A comparison of encephalization between odontocete cetaceans and anthropoid primates. Brain Behav. Evol. 51, 230–238 (1998).

  21. 21.

    , , & How many neurons do you have? Some dogmas of quantitative neuroscience under revision. Eur. J. Neurosci. 35, 1–9 (2011).

  22. 22.

    The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost. Proc. Natl Acad. Sci. USA 109 (Suppl. 1), 10661–10668 (2012).

  23. 23.

    et al. Fetal brain development in chimpanzees versus humans. Curr. Biol. 22, R791–R792 (2012).

  24. 24.

    Brain growth, life history, and cognition in primate and human evolution. Am. J. Primatol. 62, 139–164 (2004).

  25. 25.

    & Ponce de León, M. S. The evolution of hominin ontogenies. Semin. Cell Dev. Biol. 21, 441–452 (2010). A review of the studies and debate on comparative developmental trajectories between humans and other primates.

  26. 26.

    , , & Humans and great apes share a large frontal cortex. Nature Neurosci. 5, 272–276 (2002).

  27. 27.

    Absolute brain size: did we throw the baby out with the bathwater? Proc. Natl Acad. Sci. USA 103, 13563–13564 (2006).

  28. 28.

    et al. Evolution of increased glia–neuron ratios in the human frontal cortex. Proc. Natl Acad. Sci. USA 103, 13606–13611 (2006).

  29. 29.

    et al. Spatial organization of neurons in the frontal pole sets humans apart from great apes. Cereb. Cortex 21, 1485–1497 (2011).

  30. 30.

    et al. Uniquely hominid features of adult human astrocytes. J. Neurosci. 29, 3276–3287 (2009).

  31. 31.

    et al. Neuropil distribution in the cerebral cortex differs between humans and chimpanzees. J. Comp. Neurol. 520, 2917–2929 (2012).

  32. 32.

    et al. The evolution of the arcuate fasciculus revealed with comparative DTI. Nature Neurosci. 11, 426–428 (2008). This study compares human and chimpanzee cortices using diffusion tensor imaging and reports a prominent human-specific change in temporal connectivity.

  33. 33.

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

  34. 34.

    et al. The bonobo genome compared with the chimpanzee and human genomes. Nature 486, 527–531 (2012).

  35. 35.

    et al. Generation times in wild chimpanzees and gorillas suggest earlier divergence times in great ape and human evolution Proc. Natl Acad. Sci. USA 109, 15716–15721 (2012).

  36. 36.

    et al. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428, 493–521 (2004).

  37. 37.

    Nonadaptive processes in primate and human evolution. Am. J. Phys. Anthropol. 143 (Suppl. 51), 13–45 (2010).

  38. 38.

    , & Genetic basis of human brain evolution. Trends Neurosci. 31, 637–644 (2008). A comprehensive summary of brain-related genetic changes in human evolution, including protein-coding changes, duplications and regulatory changes.

  39. 39.

    et al. A draft sequence of the Neandertal genome. Science 328, 710–722 (2010).

  40. 40.

    et al. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, 1053–1060 (2010).

  41. 41.

    , , & Accelerated evolution of conserved noncoding sequences in humans. Science 314, 786 (2006).

  42. 42.

    et al. Natural selection on protein-coding genes in the human genome. Nature 437, 1153–1157 (2005).

  43. 43.

    et al. Forces shaping the fastest evolving regions in the human genome. PLoS Genet. 2, e168 (2006).

  44. 44.

    , , , & Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution. Nature Genet. 39, 1140–1144 (2007).

  45. 45.

    et al. Human-specific loss of regulatory DNA and the evolution of human-specific traits. Nature 471, 216–219 (2011).

  46. 46.

    et al. Positive natural selection in the human lineage. Science 312, 1614–1620 (2006).

  47. 47.

    , & How culture shaped the human genome: bringing genetics and the human sciences together. Nature Rev. Genet. 11, 137–148 (2010).

  48. 48.

    & Gene regulation and the origins of human biological uniqueness. Trends Genet. 26, 110–118 (2010).

  49. 49.

    et al. Human-specific transcriptional networks in the brain. Neuron 75, 601–617 (2012).

  50. 50.

    , , , & RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res. 18, 1509–1517 (2008).

  51. 51.

    et al. Diversity of microRNAs in human and chimpanzee brain. Nature Genet. 38, 1375–1377 (2006).

  52. 52.

    , , , & Identification of novel exons and transcribed regions by chimpanzee transcriptome sequencing. Genome Biol. 11, R78 (2010).

  53. 53.

    et al. Both noncoding and protein-coding RNAs contribute to gene expression evolution in the primate brain. Genome Biol. Evol. 2010, 67 (2010).

  54. 54.

    et al. Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq. PLoS Comput. Biol. 6, e1000843 (2010).

  55. 55.

    et al. Evolution of the human-specific microRNA miR-941. Nature Commun. 3, 1145 (2012).

  56. 56.

    et al. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).

  57. 57.

    & Metabolomics: a global biochemical approach to the study of central nervous system diseases. Neuropsychopharmacology 34, 173–186 (2009).

  58. 58.

    et al. Intra- and interspecific variation in primate gene expression patterns. Science 296, 340–343 (2002).

  59. 59.

    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).

  60. 60.

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

  61. 61.

    & Evolution at two levels in humans and chimpanzees. Science 188, 107–116 (1975). A classic paper that put forward the hypothesis that human brain evolution involved gene expression differences, probably during development, rather than changes in protein sequence.

  62. 62.

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

  63. 63.

    et al. A neutral model of transcriptome evolution. PLoS Biol. 2, e132 (2004).

  64. 64.

    , , & Evolution of primate gene expression. Nature Rev. Genet. 7, 693–702 (2006). A review of the first half decade of comparative transcriptome studies, describing how patterns of gene expression differences among primates are shaped by positive selection, negative selection and neutral drift.

  65. 65.

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

  66. 66.

    , & Conservation and evolution of gene coexpression networks in human and chimpanzee brains. Proc. Natl Acad. Sci. USA 103, 617973–617978 (2006). This paper introduces the use of co-expressed gene groups for analysing species transcriptome data.

  67. 67.

    , , , & Changing brains, changing perspectives: the neurocognitive development of reciprocity. Psychol. Sci. 22, 60–70 (2011).

  68. 68.

    & Resisting the power of temptations: the right prefrontal cortex and self-control. Ann. NY Acad. Sci. 1104, 123–134 (2007).

  69. 69.

    & A review of EEG, ERP, and neuroimaging studies of creativity and insight. Psychol. Bull. 136, 822–848 (2010).

  70. 70.

    & Neuroimaging studies of language production and comprehension. Annu. Rev. Psychol. 54, 91–114 (2003).

  71. 71.

    Bilingual and multilingual language processing. J. Physiol. Paris 99, 355–369 (2006).

  72. 72.

    , & Function and localization within rostral prefrontal cortex (area 10). Phil. Trans. R. Soc. B 362, 887–899 (2007).

  73. 73.

    & Broca's area: rethinking classical concepts from a neuroscience perspective. Top. Stroke Rehabil. 17, 401–410 (2010).

  74. 74.

    & Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey. Eur. J. Neurosci. 16, 291–310 (2002).

  75. 75.

    , , & The prefrontal cortex: comparative architectonic organization in the human and the macaque monkey brains. Cortex 48, 46–57 (2012).

  76. 76.

    , & Orofacial somatomotor responses in the macaque monkey homologue of Broca's area. Nature 435, 1235–1238 (2005).

  77. 77.

    , , & Communicative signaling activates 'Broca's' homolog in chimpanzees. Curr. Biol. 18, 343–348 (2008). This study demonstrates that an area in the chimpanzee brain that is homologous to Broca's area (which is involved in language in humans) is activated during gesture-based signalling.

  78. 78.

    et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391–399 (2012).

  79. 79.

    Functional brain development in humans. Nature Rev. Neurosci. 2, 475–483 (2001).

  80. 80.

    & Concise Encyclopedia of Special Education (John Wiley and Sons, 2004).

  81. 81.

    Origins of Human Communication (MIT Press, 2008).

  82. 82.

    et al. Transcriptional neoteny in the human brain. Proc. Natl Acad. Sci. USA 106, 5743–5748 (2009).

  83. 83.

    Ontogeny and Phylogeny (Harvard Univ. Press, 1977).

  84. 84.

    et al. MicroRNA-driven developmental remodeling in the brain distinguishes humans from other primates. PLoS Biol. 9, e1001214 (2011).

  85. 85.

    et al. Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques. Genome Res. 22, 611–622 (2012). This paper reports an extreme delay in synaptic maturation in the human PFC compared to other primates. The study further predicts the regulatory network involved in this change.

  86. 86.

    , , & Synaptogenesis in human visual cortex — evidence for synapse elimination during normal development. Neurosci. Lett. 33, 247–252 (1982).

  87. 87.

    , , , & Synaptophysin and postsynaptic density protein 95 in the human prefrontal cortex from mid-gestation into early adulthood. Neuroscience 149, 582–591 (2007).

  88. 88.

    & Regional differences in synaptogenesis in human cerebral cortex. J. Comp. Neurol. 387, 167–178 (1997).

  89. 89.

    , , , & Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science 232, 232–235 (1986).

  90. 90.

    , , , & Increased cortical expression of two synaptogenic thrombospondins in human brain evolution. Cereb. Cortex 17, 2312–2321 (2007).

  91. 91.

    et al. Spatio-temporal transcriptome of the human brain. Nature 478, 483–489 (2011).

  92. 92.

    , & Mapping brain maturation. Trends Neurosci. 29, 148–159 (2006).

  93. 93.

    et al. Neurodevelopmental trajectories of the human cerebral cortex. J. Neurosci. 28, 3586 (2008).

  94. 94.

    et al. Prolonged myelination in human neocortical evolution. Proc. Natl Acad. Sci. USA 109, 16480–16485 (2012). This recent study reports that the prolonged myelinization process, which is known to extend into the third and fourth decades in humans, subsides by sexual maturity in chimpanzees and thus could represent another extreme case of delayed human neurodevelopment.

  95. 95.

    Sequence of Myelinization in the Brain of Macaca mulatta. Thesis, Univ. of California (1970).

  96. 96.

    et al. Differential prefrontal white matter development in chimpanzees and humans. Curr. Biol. 21, 1397–1402 (2011).

  97. 97.

    , & The conservation and evolutionary modularity of metabolism. Genome Biol. 10, R63 (2009).

  98. 98.

    , & Ratio of central nervous system to body metabolism in vertebrates: its constancy and functional basis. Am. J. Physiol. 241, R203–R212 (1981).

  99. 99.

    et al. Age-related changes in cerebral blood flow and glucose metabolism in conscious rhesus monkeys. Brain Res. 936, 76–81 (2002).

  100. 100.

    Global and regional brain metabolic scaling and its functional consequences. BMC Biol. 5, 18 (2007).

  101. 101.

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

  102. 102.

    & Birth and adaptive evolution of a hominoid gene that supports high neurotransmitter flux. Nature Genet. 36, 1061–1063 (2004).

  103. 103.

    , , , & Properties and molecular evolution of human GLUD2 (neural and testicular tissue-specific) glutamate dehydrogenase. J. Neurosci. Res. 85, 3398–3406 (2007).

  104. 104.

    , , & Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection. PLoS Genet. 4, e1000150 (2008).

  105. 105.

    et al. Metabolic changes in schizophrenia and human brain evolution. Genome Biol. 9, R124 (2008).

  106. 106.

    et al. Role of lactate in the brain energy metabolism: revealed by bioradiography. Neurosci. Res. 48, 13–20 (2004).

  107. 107.

    et al. Rapid metabolic evolution in human prefrontal cortex. Proc. Natl Acad. Sci. USA 108, 6181–6186 (2011).

  108. 108.

    et al. Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc. Natl Acad. Sci. USA 95, 316–321 (1998).

  109. 109.

    & Maturational changes in cerebral function in infants determined by 18FDG positron emission tomography. Science 231, 840–843 (1986).

  110. 110.

    et al. A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice. Cell 137, 961–971 (2009).

  111. 111.

    et al. Human-specific transcriptional regulation of CNS development genes by FOXP2. Nature 462, 213–217 (2009). The authors show that the two human-specific amino acid changes in FOXP2 can cause differential expression in cell lines, which overlaps with human and chimpanzee brain expression differences.

  112. 112.

    , & Comparative studies of gene expression and the evolution of gene regulation. Nature Rev. Genet. 13, 505–516 (2012).

  113. 113.

    , , & Contrasts between adaptive coding and noncoding changes during human evolution. Proc. Natl Acad. Sci. USA 107, 7853–7857 (2010). A meta-analysis of genome-scans for human-specific changes in protein-coding sequence and cis -regulatory changes. They find that human-specific genetic changes in neural genes mainly involve cis -regulatory but not protein-coding changes.

  114. 114.

    et al. Genes expressed in specific areas of the human fetal cerebral cortex display distinct patterns of evolution. PLoS ONE 6, e17753 (2011).

  115. 115.

    , , & Cluster analysis and display of genome-wide expression patterns. Proc. Natl Acad. Sci. USA 95, 14863–14868 (1998).

  116. 116.

    , , , & A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413, 519–523 (2001).

  117. 117.

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

  118. 118.

    , , & Accelerated recruitment of new brain development genes into the human genome. PLoS Biol. 9, e1001179 (2011).

  119. 119.

    , , & Differences in human and chimpanzee gene expression patterns define an evolving network of transcription factors in brain. Proc. Natl Acad. Sci. USA 106, 22358–22363 (2009).

  120. 120.

    & When brain clocks lose track of time: cause or consequence of neuropsychiatric disorders. Curr. Opin. Neurobiol. 21, 849–857 (2011).

  121. 121.

    , & How necessary is the activation of the immediate early gene zif268 in synaptic plasticity and learning? Behav. Brain Res. 142, 17–30 (2003).

  122. 122.

    et al. Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311, 1008–1012 (2006).

  123. 123.

    et al. A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science 311, 1012–1017 (2006).

  124. 124.

    et al. Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory. Mol. Cell. Neurosci. 35, 76–88 (2007).

  125. 125.

    et al. Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection. Neuron 60, 1022–1038 (2008).

  126. 126.

    The neuronal microRNA system. Nature Rev. Neurosci. 7, 911–920 (2006).

  127. 127.

    MicroRNAs at the synapse. Nature Rev. Neurosci. 10, 842–849 (2009).

  128. 128.

    & Lowly expressed human microRNA genes evolve rapidly. Mol. Biol. Evol. 26, 1195–1198 (2009).

  129. 129.

    et al. MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome Res. 20, 1207–1218 (2010).

  130. 130.

    et al. MicroRNA expression and regulation in human, chimpanzee, and macaque brains. PLoS Genet. 7, e1002327 (2011).

  131. 131.

    et al. Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell Stem Cell 6, 433–444 (2010).

  132. 132.

    , , & Decoding the epigenetic language of neuronal plasticity. Neuron 60, 961–974 (2008).

  133. 133.

    et al. Epigenetics in the human brain. Neuropsychopharmacology 38, 183–197 (2012).

  134. 134.

    et al. Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution. Am. J. Hum. Genet. 91, 455–465 (2012).

  135. 135.

    et al. Human-specific histone methylation signatures at transcription start sites in prefrontal neurons. PLoS Biol. 10, e1001427 (2012). The first genome-wide analysis of histone modification differences among human, chimpanzee and macaque brains. It identified hundreds of H3K4me3 differences, some of which included genes associated with neurological disorders.

  136. 136.

    et al. Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet. 82, 477–488 (2008).

  137. 137.

    et al. Global analysis of alternative splicing differences between humans and chimpanzees. Genes Dev. 21, 2963–2975 (2007).

  138. 138.

    et al. Evolution of alternative splicing in primate brain transcriptomes. Hum. Mol. Genet. 19, 2958–2973 (2010).

  139. 139.

    et al. Adenosine-to-inosine RNA editing shapes transcriptome diversity in primates. Proc. Natl Acad. Sci. USA 107, 12174–12179 (2010).

  140. 140.

    et al. Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing. Science 324, 1210–1213 (2009).

  141. 141.

    , , & Large-scale mRNA sequencing determines global regulation of RNA editing during brain development. Genome Res. 19, 978–986 (2009).

  142. 142.

    et al. An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443, 167–172 (2006).

  143. 143.

    et al. Functionality of intergenic transcription: an evolutionary comparison. PLoS Genet. 2, e171 (2006).

  144. 144.

    , & Explaining human uniqueness: genome interactions with environment, behaviour and culture. Nature Rev. Genet. 9, 749–763 (2008).

  145. 145.

    Flaked stones and old bones: biological and cultural evolution at the dawn of technology. Am. J. Phys. Anthropol. Suppl. 39, 118–164 (2004).

  146. 146.

    Evolution of the size and functional areas of the human brain. Annu. Rev. Anthropol. 35, 379–406 (2006).

  147. 147.

    Brain size and encephalization in early to Mid-Pleistocene Homo. Am. J. Phys. Anthropol. 124, 109–123 (2004).

  148. 148.

    Natural history of Homo erectus. Am. J. Phys. Anthropol. 122 (Suppl. 37), 126–170 (2003).

  149. 149.

    , & Mitochondrial DNA and human evolution. Nature 325, 31–36 (1987).

  150. 150.

    Stone toolmaking and the evolution of human culture and cognition. Phil. Trans. R. Soc. B. 366, 1050–1059 (2011).

  151. 151.

    et al. An earlier origin for the Acheulian. Nature 477, 82–85 (2011).

  152. 152.

    , , & Phylogenetic rate shifts in feeding time during the evolution of Homo. Proc. Natl Acad. Sci. USA 108, 14555–14559 (2011).

  153. 153.

    , & Energetics and the evolution of human brain size. Nature 480, 91–93 (2011).

  154. 154.

    , , , & Genomic signatures of diet-related shifts during human origins. Proc. Biol. Sci. 278, 961–969 (2011).

  155. 155.

    et al. A new small-bodied hominin from the Late Pleistocene of Flores, Indonesia. Nature 431, 1055–1061 (2004).

  156. 156.

    et al. Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation. Cell 149, 923–935 (2012). Together with reference 157, this paper shows how a human-specific duplication in recent human history may have lead to prolonged neurodevelopment and increased spine density.

  157. 157.

    et al. Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication. Cell 149, 912–922 (2012).

  158. 158.

    et al. The derived FOXP2 variant of modern humans was shared with Neandertals. Curr. Biol. 17, 1908–1912 (2007).

  159. 159.

    et al. A high-coverage genome sequence from an archaic Denisovan individual. Science 338, 222–226 (2012).

  160. 160.

    et al. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418, 869–872 (2002).

  161. 161.

    Human evolution and cognition. Theory Biosci. 129, 193–201 (2010).

  162. 162.

    , & Stratigraphic placement and age of modern humans from Kibish, Ethiopia. Nature 433, 733–736 (2005).

  163. 163.

    & The revolution that wasn't: a new interpretation of the origin of modern human behavior. J. Hum. Evol. 39, 453–563 (2000).

  164. 164.

    , & Middle Stone Age bone tools from the Howiesons Poort Layers, Sibudu Cave, South Africa. J. Archaeol. Sci. 35, 1566–1580 (2008).

  165. 165.

    et al. An early and enduring advanced technology originating 71,000 years ago in South Africa. Nature 491, 590–593 (2012).

  166. 166.

    et al. Early human use of marine resources and pigment in South Africa during the Middle Pleistocene. Nature 449, 905–908 (2007).

  167. 167.

    et al. Emergence of modern human behavior: Middle Stone Age engravings from South Africa. Science 295, 1278–1280 (2002).

  168. 168.

    Neanderthals and the modern human colonization of Europe. Nature 432, 461–465 (2004).

  169. 169.

    et al. Symbolic use of marine shells and mineral pigments by Iberian Neandertals. Proc. Natl Acad. Sci. USA 107, 1023–1028 (2010).

  170. 170.

    Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues (J. A. Barth, 1909).

  171. 171.

    , , & Neuronal subtype specification in the cerebral cortex. Nature Rev. Neurosci. 8, 427–437 (2007).

  172. 172.

    , , & The determination of projection neuron identity in the developing cerebral cortex. Curr. Opin. Neurobiol. 18, 28–35 (2008).

  173. 173.

    & New insights into cortical interneurons development and classification: contribution of developmental studies. Dev. Neurobiol. 71, 34–44 (2011).

  174. 174.

    et al. Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures. Cell 149, 483–496 (2012).

  175. 175.

    et al. Transcriptional architecture of the primate neocortex. Neuron 73, 1083–1099 (2012).

  176. 176.

    et al. A transcriptomic atlas of mouse neocortical layers. Neuron 71, 605–616 (2011).

  177. 177.

    & Differential expansion of neural projection systems in primate brain evolution. Neuroreport 10, 1453–1459 (1999).

  178. 178.

    , , & Connectivity-driven white matter scaling and folding in primate cerebral cortex. Proc. Natl Acad. Sci. USA 107, 19008–19013 (2010).

  179. 179.

    A cytoarchitectural study of the prefrontal area of the macaque monkey. J. Comp. Neurol. 73, 59–86 (1940).

  180. 180.

    Rethinking mammalian brain evolution. Am. Zool. 30, 629–705 (1990).

  181. 181.

    & Linked regularities in the development and evolution of mammalian brains. Science 268, 1578–1584 (1995). This work demonstrates how evolutionary changes in brain size follow common rules across mammals.

  182. 182.

    et al. Extraordinary neoteny of synaptic spines in the human prefrontal cortex. Proc. Natl Acad. Sci. USA 108, 13281–13286 (2011).

  183. 183.

    Childhood, adolescence, and longevity: a multilevel model of the evolution of reserve capacity in human life history. Am. J. Hum. Biol. 21, 567–577 (2009).

  184. 184.

    , & Cognition without control: when a little frontal lobe goes a long way. Curr. Dir. Psychol. Sci. 18, 259–263 (2009).

  185. 185.

    et al. Earliest evidence of modern human life history in North African early Homo sapiens. Proc. Natl Acad. Sci. USA 104, 6128–6133 (2007).

  186. 186.

    et al. Dental evidence for ontogenetic differences between modern humans and Neanderthals. Proc. Natl Acad. Sci. USA 107, 20923–20928 (2010).

  187. 187.

    , , , & Rapid dental development in a Middle Paleolithic Belgian Neanderthal. Proc. Natl Acad. Sci. USA 104, 20220–20225 (2007).

  188. 188.

    et al. How Neanderthal molar teeth grew. Nature 444, 748–751 (2006).

  189. 189.

    Tooth microstructure tracks the pace of human life-history evolution. Proc. Biol. Sci. 273, 2799–2808 (2006).

  190. 190.

    et al. Linkage disequilibrium extends across putative selected sites in FOXP2. Mol. Biol. Evol. 26, 2181–2184 (2009).

  191. 191.

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

  192. 192.

    et al. Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genet. 4, e1000083 (2008).

  193. 193.

    & The hitch-hiking effect of a favourable gene. Genet. Res. 23, 23–35 (1974).

  194. 194.

    et al. Rate of de novo mutations and the importance of father's age to disease risk. Nature 488, 471–475 (2012).

  195. 195.

    et al. Growth rates and life histories in twenty-two small-scale societies. Am. J. Hum. Biol. 18, 295–311 (2006).

  196. 196.

    Evolution in Mendelian populations. Genetics 16, 97–159 (1931).

  197. 197.

    A mathematical theory of natural and artificial selection, part V: selection and mutation. Proc. Cambridge Phil. Soc. 23, 838–844 (1927).

  198. 198.

    & The average number of generations until fixation of a mutant gene in a finite population. Genetics 61, 763–771 (1969).

  199. 199.

    et al. Genetic signatures of strong recent positive selection at the lactase gene. Am. J. Hum. Genet. 74, 1111–1120 (2004).

  200. 200.

    et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nature Genet. 39, 31–40 (2007).

  201. 201.

    , , & Map of recent positive selection in the human genome. PLoS Biol. 4, e72 (2006).

  202. 202.

    , , , & Recent and ongoing selection in the human genome. Nature Rev. Genet. 8, 857–868 (2007).

  203. 203.

    , & The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Curr. Biol. 20, R208–R215 (2010).

  204. 204.

    Allelic genealogy and human evolution. Mol. Biol. Evol. 10, 2–22 (1993).

  205. 205.

    On the probability of fixation of mutant genes in a population. Genetics 47, 713–719 (1962).

  206. 206.

    et al. Targeted investigation of the Neandertal genome by array-based sequence capture. Science 328, 723–725 (2010).

Download references

Acknowledgements

We thank F. Kaya, N. Singh, E.-H. Sanchez, R. Nielsen, K. Bozek and J. Boyd-Kirkup for suggestions and help in preparation of this manuscript. The authors' studies are supported by the Ministry of Science and Technology of the People's Republic of China (grant number S2012GR0368), Chinese Academy of Sciences (grant numbers KSCX2-EW-R-02-02, KSCX2-EW-J-15-03 and KSCX2-EW-J-15-02), National Natural Science Foundation of China (grant number 31171232) and the Max Planck-Society. M. S. is funded by a fellowship from the European Molecular Biology Organization (EMBO ALTF 1475–2010).

Author information

Affiliations

  1. CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, 320 Yue Yang Road, Shanghai, 200031, China.

    • Mehmet Somel
    • , Xiling Liu
    •  & Philipp Khaitovich
  2. Department of Integrative Biology, University of California Berkeley, Berkeley, California 94820, USA.

    • Mehmet Somel
  3. Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, 04103, Germany.

    • Philipp Khaitovich

Authors

  1. Search for Mehmet Somel in:

  2. Search for Xiling Liu in:

  3. Search for Philipp Khaitovich in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Philipp Khaitovich.

Glossary

Neuropile

A synaptically dense region between the neuronal and glial cell bodies, composed of dendrites, axons, synapses, glial cell processes and microvasculature.

Hominid

A member of the family Hominidae (the great apes), including the subfamily Homininae (humans, gorillas and chimpanzees) and the subfamily Ponginae (orang-utans).

Hominin

Member of the tribe Hominini, including all species that evolved since the last common ancestor between humans and chimpanzees, and which were more closely related to humans than to chimpanzees, including the genera Ardipithecus, Australopithecus, Paranthropus and Homo.

Neanderthals

An extinct species of the genus Homo, which inhabited Europe and parts of western Asia between 400,000 and 30,000 years ago. Notably, they had very similar morphology to modern humans, slightly bigger brains, and interbred with Eurasian modern humans for some period.

Denisovans

A recently discovered extinct Homo species identified by genome sequencing of a finger bone from Siberia. Denisovans were more closely related to Neanderthals than to modern humans.

mRNAs

Transcripts encoding sequences of protein-coding genes. mRNAs serve as messengers between genomic DNA and the protein translation machinery of the cell.

Non-coding RNAs

(ncRNAs). Transcripts that do not encode proteins but have regulatory, structural and catalytic roles in cells.

Broca's area

A region of the brain within the inferior frontal gyrus that is associated with speech in humans and manual gestures in other primates. The region tends to be larger in the left hemisphere.

Heterochrony

An evolutionary phenomenon involving changes in the rate and timing of development.

Synaptogenesis

The formation of synapses between neurons. In the human cerebrum, synaptogenesis is especially intense starting from 30 weeks of pregnancy until 15 months of age.

Synaptic elimination

Also called synaptic pruning, this is the developmental process whereby immature synapses — that is, those not subject to activity-dependent strengthening — are removed. At least half of the synapses generated in the infant cortex are eventually eliminated.

Neoteny

A type of evolutionary change in timing — that is, heterochrony — brought about by a retardation of somatic development, resulting in adult features characteristic of the juvenile state of ancestors.

Hominoid

Member of the superfamily Hominoidea, which contains two families of extant species — the family Hominidae (the great apes, including humans, orang-utans, gorillas, chimpanzees and bonobos) and the family Hylobatidae (lesser apes, including gibbons).

Transcription factors

Proteins activating or repressing the expression of genes by binding to particular DNA sequence motifs proximal to a gene's transcription start site.

MicroRNAs

(miRNAs). miRNAs are commonly single-stranded RNA molecules of 20–23 nucleotides in length, generated endogenously from a single-stranded hairpin precursor. They act as post-transcriptional inhibitors in association with the RNA-induced silencing complex (RISC).

Cis-elements

DNA sequences, such as a transcription binding site, directly affecting the expression of a gene within the same chromosomal region.

Trans-regulator

An RNA or protein that regulates the expression of another, so-called target gene. Unlike a cis-element, it does not necessarily reside in the same chromosomal region as the target gene.

Neutral mutation

A mutation that has no effect on evolutionary fitness: that is, it is neither positively nor negatively selected, so its frequency changes only as a result of genetic drift.

Genetic drift

Random sampling effects, such as random variance in the number of offspring among individuals, that can increase or decrease a mutation's frequency in a population across generations. Such events can cause the loss or, more rarely, fixation of a neutral or nearly neutral mutation.

Zinc finger proteins

A family of proteins containing a zinc finger motif, where zinc ions take part in stabilizing the structure, and which usually function in DNA or RNA binding. The largest family of mammalian transcription factors consists of zinc finger proteins.

RNA editing

A molecular process in which the information content in an RNA molecule is altered through a chemical change in the base make-up at the post-transcriptional level.

RNA-binding proteins

Proteins that bind to RNAs through an RNA-binding motif. The binding may regulate the translation of RNA or induce post-transcriptional changes, such as RNA splicing and editing.

PIWI-interacting RNA

(piRNA). A class of small non-coding RNA molecules of 26–31 nucleotides in length with a bias for a 5′ uridine, which is abundant in the germ line and has been implicated in the maintenance of genomic integrity by both epigenetic and post-transcriptional silencing of transposable elements and other genetic elements.

Large intergenic non-coding RNA

(lincRNA). Non-protein coding transcripts of more than 200 nucleotides in length, which are characterized by the complexity and diversity of their sequences. lincRNAs have emerged as key molecules involved in the control of transcriptional and post-transcriptional gene regulatory pathways.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nrn3372