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Principal Investigator
Bing Su   Ph.D  
Title
Phone +86 871 65120212
Fax +86 871 65120212
E-mail sub@mail.kiz.ac.cn
Address Kunming Institute of Zoology, the Chinese Academy of Sciences No. 32 Jiaochang Donglu, Kunming, Yunnan, 650223, P.R.China
Zip Code 650223
 
   Education and Appointments:

Dr. Bing Su, principal investigator, The enlarged brain and highly developed cognitive skills are the most significant characteristics that set us apart from our relatives, the non-human primates. This evolutionary expansion is believed to be crucial to the highly developed cognitive abilities in humans, yet its genetic basis remains unsolved. our laboratory focuses on the genetic mechanism underlying the dramatic enlargement of human brain and its highly developed cognitive skills during human evolution.

  Professional Services
   Research Interests:

Genetic mechanism underlying primate brain evolution 
The enlarged brain and highly developed cognitive skills are the most significant characteristics that set us apart from our relatives, the non-human primates. The brains of modern humans are more than 20 times larger than those of Old World monkeys, and more than four times larger than those of great apes. This evolutionary expansion is believed to be crucial to the highly developed cognitive abilities in humans, yet its genetic basis remains unsolved. To understand the genetic basis shaping up the phenotypic characteristics  such as enlarged brain as well as highly developed cognitive skills of humans comparing to its relative, Chimpanzee, we analyzed  sequence variation and  gene expression of human brain-expressed genes in diverse non-human primate species, we identified 47 candidate genes showing strong evidence of positive selection in the human lineage. Genes with maximal expression in the brain showed a higher evolutionary rate in human than in chimpanzee. We observed that many immune-defense-related genes were under strong positive selection, and this trend was more prominent in chimpanzee than in human.
Neuropsin (kallikrein 8, KLK8) is a secreted-type serine protease preferentially expressed in the central nervous system and involved in learning and memory. Its splicing pattern is different in human and mouse, with the longer form (type II) only expressed in human. Sequence analysis suggested a recent origin of type II during primate evolution. Here we demonstrate that the type II form is absent in nonhuman primates, and is thus a human-specific splice form. With the use of an in vitro splicing assay, we show that a human-specific T to A mutation (c.71–127T4A) triggers the change of splicing pattern, leading to the origin of a novel splice form in the human brain. Using mutation assay, we prove that this mutation is not only necessary but also sufficient for type II expression. Our results demonstrate a molecular mechanism for the creation of novel proteins through alternative splicing in the central nervous system during human evolution .
MicroRNAs (miRNAs) are a growing class of small RNAs (about 22 nt) that play crucial regulatory roles in the genome by targeting mRNAs for cleavage or translational repression. We analyzed two miRNA clusters located on chromosome X and 19, respectively. Our data indicate rapid evolution of this cluster in primates including frequent tandem duplications and nucleotide substitutions. We propose that, like protein-coding genes, miRNA genes involved in male reproduction are subject to rapid adaptive changes that may contribute to functional novelties during evolution. Our results also showed an evidence of an Alu-mediated rapid expansion of miRNA genes in a previously identified primate-specific miRNA family, drawn from sequencing and comparative analysis of 9 diverse primate species. Evolutionary analysis reveals similar divergence among miRNA copies whether they are within or between species, lineage-specific gain and loss of miRNAs, and gene pseudolization in multiple species. These observations support a birth-and-death process of miRNA genes in this family, implicating functional diversification during primate evolution.

  Supported Projects:
  Public Services:
  Honors:

1996 The award of natural science research of the Chinese Academy of Sciences
1997 The national award of natural science research of China
2002 The award of natural science research of Yunnan province of China
2003 The award of natural science research of ministry of education, China
2006 The award of natural science research of Yunnan province of China

  Selected Publications:

1.         Su, B. et al. Y-Chromosome evidence for a northward migration of modern humans into Eastern Asia during the last Ice Age. Am J Hum Genet 65, 1718-24. (1999)

2.         Jin, L. & Su, B. Natives or immigrants: modern human origin in east Asia. Nat Rev Genet 1, 126-33. (2000)

3.         Su, B., Jin, L., Underhill, P., Martinson, J., Saha, N., McGarvey, S.T., Shriver, M.D., Chu, J., Oefner, P., Chakraborty, R. & Deka, R. Polynesian origins: insights from the Y chromosome. Proc Natl Acad Sci U S A 97, 8225-8. (2000)

4.         Ke, Y.H. Su, B.(co-first authors), et al. African origin of modern humans in East Asia: A tale of 12,000 Y chromosomes. Science 292, 1151-1153. (2001)

5.         Li, Y., Qian, Y.P., Yu, X.J., Wang, Y.Q., Dong, D.G., Sun, W., Ma, R.M. & Su, B.* Recent origin of a hominoid-specific splice form of neuropsin, a gene involved in learning and memory. Mol Biol Evol 21, 2111-5. (2004)

6.         Wang, Y.Q. & Su, B.* Molecular evolution of microcephalin, a gene determining human brain size. Hum Mol Genet 13, 1131-7. (2004)

7.         Wen, B., Li, H., Lu, D., Song, X., Zhang, F., He, Y., Li, F., Gao, Y., Mao, X., Zhang, L., Qian, J., Tan, J., Jin, J., Huang, W., Deka, R., Su, B., Chakraborty, R. & Jin, L. Genetic evidence supports demic diffusion of Han culture. Nature 431, 302-5. (2004)

8.         Shi, H., Dong, Y.L., Wen, B., Xiao, C.J., Underhill, P.A., Shen, P.D., Chakraborty, R., Jin, L. & Su, B.* Y-chromosome evidence of southern origin of the East Asian-specific haplogroup O3-M122. Am J Hum Genet 77, 408-19. (2005)

9.         Wang, Y.Q., Qian, Y.P., Yang, S., Shi, H., Liao, C.H., Zheng, H.K., Wang, J., Lin, A.A., Cavalli-Sforza, L.L., Underhill, P.A., Chakraborty, R., Jin, L. & Su, B.* Accelerated evolution of the pituitary adenylate cyclase-activating polypeptide precursor gene during human origin. Genetics 170, 801-6. (2005)

10.      Lu, Z.X., Peng, J. & Su, B.* A human-specific mutation leads to the origin of a novel splice form of neuropsin (KLK8), a gene involved in learning and memory. Hum Mutat 28, 978-84. (2007)

11.      Zhang, R., Peng, Y., Wang, W. & Su, B.* Rapid evolution of an X-linked microRNA cluster in primates. Genome Res 17, 612-7. (2007)

12.      Shi, H., Zhong, H., Peng, Y., Dong, Y.L., Qi, X.B., Zhang, F., Liu, L.F., Tan, S.J., Ma, R.L., Xiao, C.J., Wells, S., Jin, L. & Su, B.* Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations. BMC Biol 6, 45. (2008)

13.      Wang, J.K., Li, Y. & Su, B.* A common SNP of MCPH1 is associated with cranial volume variation in Chinese population. Hum Mol Genet 17, 1329-35. (2008)

14.      Wu, H.H. & Su, B.* Adaptive evolution of SCML1 in primates, a gene involved in male reproduction. BMC Evol Biol 8, 192. (2008)

15.      Zhang, R. & Su, B.* MicroRNA regulation and the variability of human cortical gene expression. Nucleic Acids Res 36, 4621-8. (2008)

16.      Zhang, R., Wang, Y.Q. & Su, B.* Molecular evolution of a primate-specific microRNA family. Mol Biol Evol 25, 1493-502. (2008)

17.      Lu, Z.X., Huang, Q. & Su, B.* Functional characterization of the human-specific (type II) form of kallikrein 8, a gene involved in learning and memory. Cell Res 19, 259-67. (2009)

18.      Shi, H., Tan, S.J., Zhong, H., Hu, W., Levine, A., Xiao, C.J., Peng, Y., Qi, X.B., Shou, W.H., Ma, R.L., Li, Y., Su, B.* & Lu, X. Winter temperature and UV are tightly linked to genetic changes in the p53 tumor suppressor pathway in Eastern Asia. Am J Hum Genet 84, 534-41. (2009)

19.      Peng, Y., Shi, H., Qi, X.B., Xiao, C.J., Zhong, H., Ma, R.L. & Su, B.* The ADH1B Arg47His polymorphism in east Asian populations and expansion of rice domestication in history. BMC Evol Biol 10, 15. (2010)

20.      Zhong, H., Shi, H., Qi, X.B., Xiao, C.J., Jin, L., Ma, R.Z. & Su, B.* Global distribution of Y-chromosome haplogroup C reveals the prehistoric migration routes of African exodus and early settlement in East Asia. J Hum Genet 55, 428-35. (2010)

21.       Peng, Y., Yang, Z., Zhang, H., Cui, C., Qi, X., Luo, X., Tao, X., Wu, T., Ouzhuluobu, Basang, Ciwangsangbu, Danzengduojie, Chen, H., Shi, H. & Su, B.* Genetic variations in Tibetan populations and high-altitude adaptation at the Himalayas. Mol Biol Evol 28, 1075-81. (2011)

22.       Zhong, H., Shi, H., Qi, X.B., Duan, Z.Y., Tan, P.P., Jin, L., Su, B.* & Ma, R.Z.* Extended Y-chromosome investigation suggests post-Glacial migrations of modern humans into East Asia via the northern route. Mol Biol Evol 28, 717-727. (2011)       

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