Abstract
Rapidly advancing knowledge of genome structure and sequence enables new means for the analysis of specific DNA changes associated with the differences between the human brain and that of other mammals. Recent studies implicate evolutionary changes in messenger RNA and protein expression levels, as well as DNA changes that alter amino acid sequences. We can anticipate having a systematic catalogue of DNA changes in the lineage leading to humans, but an ongoing challenge will be relating these changes to the anatomical and functional differences between our brain and that of our ancient and more recent ancestors.
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References
Ramon y Cajal, S. Recuerdos de mi Vida Vol. 2 Historia de mi Labour Científica 345–346 (Moya, Madrid, 1917)
Carroll, S. B. Genetics and the making of Homo sapiens. Nature 422, 849–857 (2003)
Kornack, D. R. & Rakic, P. Changes in cell-cycle kinetics during the development and evolution of primate neocortex. Proc. Natl Acad. Sci. USA 95, 1242–1246 (1998)
Takahashi, T., Nowakowski, R. S. & Caviness, V. S. Jr. The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall. J. Neurosci. 15, 6046–6057 (1995)
Marin-Padilla, M. Ontogenesis of the pyramidal cell of the mammalian neocortex and developmental cytoarchitectonics: a unifying theory. J. Comp. Neurol. 321, 223–240 (1992)
Allman, J., Hakeem, A. & Watson, K. Two phylogenetic specializations in the human brain. Neuroscientist 8, 335–346 (2002)
Orban, G. A., Van Essen, D. & Vanduffel, W. Comparative mapping of higher visual areas in monkeys and humans. Trends Cogn. Sci. 8, 315–324 (2004)
Semendeferi, K., Lu, A., Schenker, N. & Damasio, H. Humans and great apes share a large frontal cortex. Nature Neurosci. 5, 272–276 (2002)
Hopkins, W. D. & Cantalupo, C. Handedness in chimpanzees (Pan troglodytes) is associated with asymmetries of the primary motor cortex but not with homologous language areas. Behav. Neurosci. 118, 1176–1183 (2004)
Cantalupo, C. & Hopkins, W. D. Asymmetric Broca's area in great apes. Nature 414, 505 (2001)
Sun, T. et al. Early asymmetry of gene transcription in embryonic human left and right cerebral cortex. Science 308, 1794–1798 (2005)
Broadfield, D. C. et al. Endocast of Sambungmacan 3 (Sm 3): a new Homo erectus from Indonesia. Anat. Rec. 262, 369–379 (2001)
The Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature doi:10.1038/nature04072 (this issue)
Gilad, Y., Man, O. & Glusman, G. A comparison of the human and chimpanzee olfactory receptor gene repertoires. Genome Res. 15, 224–230 (2005)
Enard, W. et al. Intra- and interspecific variation in primate gene expression patterns. Science 296, 340–343 (2002)
Caceres, M. et al. Elevated gene expression levels distinguish human from non-human primate brains. Proc. Natl Acad. Sci. USA 100, 13030–13035 (2003)
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)
Goldman, N. & Yang, Z. A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol. Biol. Evol. 11, 725–736 (1994)
Dorus, S. et al. Accelerated evolution of nervous system genes in the origin of Homo sapiens. Cell 119, 1027–1040 (2004)
Nielsen, R. et al. A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol. 3, e170 (2005)
Clark, A. G. et al. Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios. Science 302, 1960–1963 (2003)
Lai, C. S., Fisher, S. E., Hurst, J. A., Vargha-Khadem, F. & Monaco, A. P. A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413, 519–523 (2001)
Enard, W. et al. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418, 869–872 (2002)
Gilbert, S. L., Dobyns, W. B. & Lahn, B. T. Genetic links between brain development and brain evolution. Nature Rev. Genet. 6, 581–590 (2005)
Bond, J. et al. ASPM is a major determinant of cerebral cortical size. Nature Genet. 32, 316–320 (2002)
Evans, P. D., Anderson, J. R., Vallender, E. J., Choi, S. S. & Lahn, B. T. Reconstructing the evolutionary history of microcephalin, a gene controlling human brain size. Hum. Mol. Genet. 13, 1139–1145 (2004)
Evans, P. D. et al. Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Hum. Mol. Genet. 13, 489–494 (2004)
Kouprina, N. et al. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion. PLoS Biol. 2, E126 (2004)
Zhang, J. Evolution of the human ASPM gene, a major determinant of brain size. Genetics 165, 2063–2070 (2003)
Ferland, R. J. et al. Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome. Nature Genet. 36, 1008–1013 (2004)
Marin-Padilla, M. Dual origin of the mammalian neocortex and evolution of the cortical plate. Anat. Embryol. 152, 109–126 (1978)
Acknowledgements
This work was supported by grants from the NINDS and Cure Autism Now. We thank M. Ruvolo and D. Reich for comments on an earlier version of this manuscript, and J. DeFilipe for the translation of the Cajal quotation. Owing to space limitations we were unable to cite directly some of the relevant work in this field. C.A.W. is an Investigator of the Howard Hughes Medical Institute.
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Hill, R., Walsh, C. Molecular insights into human brain evolution. Nature 437, 64–67 (2005). https://doi.org/10.1038/nature04103
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DOI: https://doi.org/10.1038/nature04103
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