Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Accelerated Evolution of the Regulatory Sequences of Brain Development in the Human Genome

  • Lee, Kang Seon (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Bang, Hyoeun (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Choi, Jung Kyoon (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Kim, Kwoneel (Department of Biology, Kyung Hee University)
  • Received : 2019.11.20
  • Accepted : 2020.03.08
  • Published : 2020.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Genetic modifications in noncoding regulatory regions are likely critical to human evolution. Human-accelerated noncoding elements are highly conserved noncoding regions among vertebrates but have large differences across humans, which implies human-specific regulatory potential. In this study, we found that human-accelerated noncoding elements were frequently coupled with DNase I hypersensitive sites (DHSs), together with monomethylated and trimethylated histone H3 lysine 4, which are active regulatory markers. This coupling was particularly pronounced in fetal brains relative to adult brains, non-brain fetal tissues, and embryonic stem cells. However, fetal brain DHSs were also specifically enriched in deeply conserved sequences, implying coexistence of universal maintenance and human-specific fitness in human brain development. We assessed whether this coexisting pattern was a general one by quantitatively measuring evolutionary rates of DHSs. As a result, fetal brain DHSs showed a mixed but distinct signature of regional conservation and outlier point acceleration as compared to other DHSs. This finding suggests that brain developmental sequences are selectively constrained in general, whereas specific nucleotides are under positive selection or constraint relaxation simultaneously. Hence, we hypothesize that human- or primate-specific changes to universally conserved regulatory codes of brain development may drive the accelerated, and most likely adaptive, evolution of the regulatory network of the human brain.

Keywords

References

  1. Barton, R.A. and Venditti, C. (2014). Rapid evolution of the cerebellum in humans and other great apes. Curr. Biol. 24, 2440-2444. https://doi.org/10.1016/j.cub.2014.08.056
  2. Bejerano, G., Pheasant, M., Makunin, I., Stephen, S., Kent, W.J., Mattick, J.S., and Haussler, D. (2004). Ultraconserved elements in the human genome. Science 304, 1321-1325. https://doi.org/10.1126/science.1098119
  3. Bird, C.P., Stranger, B.E., Liu, M., Thomas, D.J., Ingle, C.E., Beazley, C., Miller, W., Hurles, M.E., and Dermitzakis, E.T. (2007). Fast-evolving noncoding sequences in the human genome. Genome Biol. 8, R118. https://doi.org/10.1186/gb-2007-8-6-r118
  4. Bush, E.C. and Lahn, B.T. (2008). A genome-wide screen for noncoding elements important in primate evolution. BMC Evol. Biol. 8, 17. https://doi.org/10.1186/1471-2148-8-17
  5. Caporale, A.L., Gonda, C.M., and Franchini, L.F. (2019). Transcriptional enhancers in the FOXP2 locus underwent accelerated evolution in the human lineage. Mol. Biol. Evol. 36, 2432-2450. https://doi.org/10.1093/molbev/msz173
  6. DeCasien, A.R., Williams, S.A., and Higham, J.P. (2017). Primate brain size is predicted by diet but not sociality. Nat. Ecol. Evol. 1, 1-7. https://doi.org/10.1038/s41559-016-0001
  7. Dimitrieva, S. and Bucher, P. (2013). UCNEbase-a database of ultraconserved non-coding elements and genomic regulatory blocks. Nucleic Acids Res. 41, D101-D109. https://doi.org/10.1093/nar/gks1092
  8. Doan, R.N., Bae, B.I., Cubelos, B., Chang, C., Hossain, A.A., Al-Saad, S., Mukaddes, N.M., Oner, O., Al-Saffar, M., Balkhy, S., et al. (2016). Mutations in human accelerated regions disrupt cognition and social behavior. Cell 167, 341-354.e12. https://doi.org/10.1016/j.cell.2016.08.071
  9. Duret, L. and Galtier, N. (2009). Comment on "Human-specific gain of function in a developmental enhancer". Science 323, 1-2.
  10. Ernst, J., Kheradpour, P., Mikkelsen, T.S., and Shoresh, N. (2011). Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473, 43-49. https://doi.org/10.1038/nature09906
  11. Heintzman, N.D., Hon, G.C., Hawkins, R.D., Kheradpour, P., Stark, A., Harp, L.F., Ye, Z., Lee, L.K., Stuart, R.K., Ching, C.W., et al. (2009). Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459, 108-112. https://doi.org/10.1038/nature07829
  12. Hill, K.K., Juang, V.B.J., and Hoffmann, F.M. (1995). Genetic interactions between the Drosophila Abelson (Abl) tyrosine kinase and failed axon connections (Fax), a novel protein in axon bundles. Genetics 141, 595-606. https://doi.org/10.1093/genetics/141.2.595
  13. Hnisz, D., Abraham, B.J., Lee, T.I., Lau, A., Saint-André, V., Sigova, A.A., Hoke, H.A., and Young, R.A. (2013). Super-enhancers in the control of cell identity and disease. Cell 155, 934-947. https://doi.org/10.1016/j.cell.2013.09.053
  14. Kamm, G.B., Pisciottano, F., Kliger, R., and Franchini, L.F. (2013). The developmental brain gene NPAS3 contains the largest number of accelerated regulatory sequences in the human genome. Mol. Biol. Evol. 30, 1088-1102. https://doi.org/10.1093/molbev/mst023
  15. Katzman, S., Kern, A.D., Pollard, K.S., Salama, S.R., and Haussler, D. (2010). GC-biased evolution near human accelerated regions. PLoS Genet. 6, e1000960. https://doi.org/10.1371/journal.pgen.1000960
  16. King, M. and Wilson, A.C. (1975). Evolution at two levels in humans and chimpanzees. Science 188, 107-116. https://doi.org/10.1126/science.1090005
  17. Kostka, D., Hubisz, M.J., Siepel, A., and Pollard, K.S. (2012). The role of GCbiased gene conversion in shaping the fastest evolving regions of the human genome. Mol. Biol. Evol. 29, 1047-1057. https://doi.org/10.1093/molbev/msr279
  18. Lindblad-Toh, K., Garber, M., Zuk, O., Lin, M.F., Parker, B.J., Washietl, S., Kheradpour, P., Ernst, J., Jordan, G., Mauceli, E., et al. (2011). A highresolution map of human evolutionary constraint using 29 mammals. Nature 478, 476-482. https://doi.org/10.1038/nature10530
  19. Lu, Y., Wang, X., Yu, H., Li, J., Jiang, Z., Chen, B., Lu, Y., Wang, W., Han, C., Ouyang, Y., et al. (2019). Evolution and comprehensive analysis of DNAseI hypersensitive sites in regulatory regions of primate brain-related genes. Front. Genet. 10, 1-12. https://doi.org/10.3389/fgene.2019.00001
  20. Maurano, M.T., Humbert, R., Rynes, E., Thurman, R.E., Haugen, E., Wang, H., Reynolds, A.P., Sandstrom, R., Qu, H., Brody, J., et al. (2012). Systematic localization of common disease-associated variation in regulatory DNA. Science 337, 1190-1195. https://doi.org/10.1126/science.1222794
  21. McLean, C.Y., Reno, P.L., Pollen, A.A., Bassan, A.I., Capellini, T.D., Guenther, C., Indjeian, V.B., Lim, X., Menke, D.B., Schaar, B.T., et al. (2011). Humanspecific loss of regulatory DNA and the evolution of human-specific traits. Nature 471, 216-219. https://doi.org/10.1038/nature09774
  22. Morreale de Escobar, G., Obregon, M.J., and Escobar del Rey, F. (2004). Role of thyroid hormone during early brain development. Eur. J. Endocrinol. 151, U25-U37. https://doi.org/10.1530/eje.0.151U025
  23. Pennacchio, L.A., Ahituv, N., Moses, A.M., and Prabhakar, S. (2006). In vivo enhancer analysis of human conserved non-coding sequences. Nature 444, 499-502. https://doi.org/10.1038/nature05295
  24. Pollard, K.S., Hubisz, M.J., Rosenbloom, K.R., and Siepel, A. (2010). Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res. 20, 110-121. https://doi.org/10.1101/gr.097857.109
  25. Pollard, K.S., Salama, S.R., King, B., Kern, A.D., Dreszer, T., Katzman, S., Siepel, A., Pedersen, J.S., Bejerano, G., Baertsch, R., et al. (2006). Forces shaping the fastest evolving regions in the human genome. PLoS Genet. 2, e168. https://doi.org/10.1371/journal.pgen.0020168
  26. Prabhakar, S., Noonan, J.P., Svante, P., and Rubin, E.M. (2006). Accelerated evolution of conserved noncoding sequences in humans. Science 314, 786. https://doi.org/10.1126/science.1130738
  27. Prabhakar, S., Visel, A., Akiyama, J.A., Shoukry, M., Lewis, K.D., Holt, A., Plajzer-Frick, I., Morrison, H., Fitzpatrick, D.R., Afzal, V., et al. (2008). Humanspecific gain of function in a developmental enhancer. Science 321, 1346-1350. https://doi.org/10.1126/science.1159974
  28. Prabhakar, S., Visel, A., Akiyama, J.A., Shoukry, M., Lewis, K.D., Holt, A., Plajzer-Frick, I., Morrison, H., FitzPatrick, D.R., Afzal, V., et al. (2009). Response to comment on "Human-specific gain of function in a developmental enhancer". Science 323, 714d. https://doi.org/10.1126/science.1166571
  29. Roth, G. (2015). Convergent evolution of complex brains and high intelligence. Philos. Trans. R. Soc. Lond. B Biol. Sci. 370, 20150049. https://doi.org/10.1098/rstb.2015.0049
  30. Sandhu, K.S., Li, G., Poh, H.M., Quek, Y.L.K., Sia, Y.Y., Peh, S.Q., Mulawadi, F.H., Lim, J., Sikic, M., Menghi, F., et al. (2012). Large-scale functional organization of long-range chromatin interaction networks. Cell Rep. 2, 1207-1219. https://doi.org/10.1016/j.celrep.2012.09.022
  31. Siepel, A., Bejerano, G., Pedersen, J.S., Hinrichs, A.S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L.W., Richards, S., et al. (2005). Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15, 1034-1050. https://doi.org/10.1101/gr.3715005
  32. Spielmann, M. and Mundlos, S. (2016). Looking beyond the genes: the role of non-coding variants in human disease. Hum. Mol. Genet. 25, R157-R165. https://doi.org/10.1093/hmg/ddw205
  33. Stein, J.L., Hua, X., Lee, S., Ho, A.J., Leow, A.D., and Toga, A.W. (2010). Voxelwise genome-wide association study (vGWAS). Neuroimage 53, 1160-1174. https://doi.org/10.1016/j.neuroimage.2010.02.032
  34. Yang, D., Jang, I., Choi, J., Kim, M.S., Lee, A.J., Kim, H., Eom, J., Kim, D., Jung, I., and Lee, B. (2018). 3DIV: a 3D-genome Interaction Viewer and database. Nucleic Acids Res. 46, D52-D57. https://doi.org/10.1093/nar/gkx1017