Abstract
Greatly expanded brain volume is one of the most characteristic traits that distinguish humans from other primates. Recent studies have revealed genes responsible for the dramatically enlarged human brain size (i.e., the microcephaly genes), and it has been well documented that many microcephaly genes have undergone accelerated evolution along the human lineage. In addition to being far larger than other primates, human brain volume is also highly variable in general populations. However, the genetic basis underlying human brain volume variation remains elusive and it is not known whether genes regulating human brain volume variation also have experienced positive selection. We have previously shown that genetic variants (near the IL3 gene) on 5q33 were significantly associated with brain volume in Chinese population. Here, we provide further evidence that support the significant association of genetic variants on 5q33 with brain volume. Bioinformatic analyses suggested that rs31480 is likely to be the causal variant among the studied SNPs. Molecular evolutionary analyses suggested that IL3 might have undergone positive selection in primates and humans. Neutrality tests further revealed signatures of positive selection of IL3 in Han Chinese and Europeans. Finally, extended haplotype homozygosity (EHH) and relative EHH analyses showed that the C allele of SNP rs31480 might have experienced recent positive selection in Han Chinese. Our results suggest that IL3 is an important genetic regulator for human brain volume variation and implied that IL3 might have experienced weak or modest positive selection in the evolutionary history of humans, which may be due to its contribution to human brain volume.
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Acknowledgments
XJL was supported by the 100 Talents Program (BaiRenJiHua) of the Kunming Institute of Zoology, Chinese Academy of Sciences, and Project of Thousand Youth Talents of China. YGY was supported by the Ministry of Science and Technology of China (2011CB910900) and the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020300). Chunhui Chen was supported by the National Natural Science Foundation of China (31100807). QD and Chuansheng Chen were supported by the 111 Project of the Ministry of Education of China (B07008).
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Ming Li, Liang Huang, Kaiqin Li and Yongxia Huo contributed equally to this work.
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Li, M., Huang, L., Li, K. et al. Adaptive evolution of interleukin-3 (IL3), a gene associated with brain volume variation in general human populations. Hum Genet 135, 377–392 (2016). https://doi.org/10.1007/s00439-016-1644-z
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DOI: https://doi.org/10.1007/s00439-016-1644-z