Expression profiles of east-west highly differentiated genes in Uyghur genomes

Zhilin Ning; Xinjiang Tan; Yuan Yuan; Ke Huang; Yuwen Pan; Lei Tian; Yan Lu; Xiaoji Wang; Ruicheng Qi; Dongsheng Lu; Yajun Yang; Yaqun Guan; Dolikun Mamatyusupu; Shuhua Xu

doi:10.1093/nsr/nwad077

Expression profiles of east-west highly differentiated genes in Uyghur genomes

Natl Sci Rev. 2023 Mar 21;10(4):nwad077. doi: 10.1093/nsr/nwad077. eCollection 2023 Apr.

Authors

Zhilin Ning¹, Xinjiang Tan¹, Yuan Yuan¹, Ke Huang^{1

2}, Yuwen Pan¹, Lei Tian¹, Yan Lu³, Xiaoji Wang¹, Ruicheng Qi¹, Dongsheng Lu¹, Yajun Yang³, Yaqun Guan⁴, Dolikun Mamatyusupu⁵, Shuhua Xu^{3

6

7}

Affiliations

¹ Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
² School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China.
³ State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China.
⁴ Department of Biochemistry and Molecular Biology, Preclinical Medicine College, Xinjiang Medical University, Urumqi 830011, China.
⁵ College of the Life Sciences and Technology, Xinjiang University, Urumqi 830046, China.
⁶ Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and Ministry of Education Key Laboratory of Contemporary Anthropology, Fudan University, Shanghai 201203, China.
⁷ Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Abstract

It remains unknown and debatable how European-Asian-differentiated alleles affect individual phenotypes. Here, we made the first effort to analyze the expression profiles of highly differentiated genes with eastern and western origins in 90 Uyghurs using whole-genome (30× to 60×) and transcriptome data. We screened 921 872 east-west highly differentiated genetic variants, of which ∼4.32% were expression quantitative trait loci (eQTLs), ∼0.12% were alternative splicing quantitative trait loci (sQTLs), and ∼0.12% showed allele-specific expression (ASE). The 8305 highly differentiated eQTLs of strong effects appear to have undergone natural selection, associated with immunity and metabolism. European-origin alleles tend to be more biasedly expressed; highly differentiated ASEs were enriched in diabetes-associated genes, likely affecting the diabetes susceptibility in the Uyghurs. We proposed an admixture-induced expression model to dissect the highly differentiated expression profiles. We provide new insights into the genetic basis of phenotypic differentiation between Western and Eastern populations, advancing our understanding of the impact of genetic admixture.

Keywords: RNASeq; Xinjiang's Uyghurs; gene expression; next-generation sequencing.