Wenyu Zhang

Evolutionary Biologist

Research

As a postdoctoral researcher (2016.11 – )

  • Evolutionary dynamics of gene retrocopies in house mouse natural populations

While the contribution of retrogenes (new genes originated from the reintegration of reverse-transcribed RNA into the genome) to genome evolution and adaptations has long been recognized, the evolutionary patterns of very recently derived gene retrocopies that are still polymorphic within natural populations have not been much studied so far. In this project, we use a unique genomic dataset from nine house mouse populations and show the biological effects of these new gene retrocopies from two distinct aspects: 1) Most new gene retrocopies show deleterious effects, mainly through interference with the expression of their parental genes; 2) A small subset of high-frequency retrocopies show signatures of positive selection, indicating their involvement in a recent adaptation process. Taken together, these two lines of work represent a comprehensive coverage of the evolutionary dynamics of gene retrocopies in a range of natural populations.

Related publication:

  1. Wenyu Zhang, Chen Xie, Kristian Ullrich, Yong E. Zhang and Diethard Tautz(#). The mutational load in natural populations is significantly affected by high primary rates of retroposition. Proc Natl Acad Sci USA. 2021Feb 9;118(6):e2013043118. doi: 10.1073/pnas.2013043118.  [Link]
  2. Wenyu Zhang(#) and Diethard Tautz. Tracing the origin and evolutionary fate of recent gene retrocopies in natural populations of the house mouse. Mol Biol Evol. 2022 Feb 3;39(2):msab360. doi: 10.1093/molbev/msab360. [Link]

  • The genetic basis of Drosophila melanogaster pupal-stage complex traits

Quantitative traits usually have a polygenic genetic basis, with a relatively small effect size from each associated genetic loci. Genome-wide association (GWA) analysis represents the main research paradigm for the detection of association variants of quantitative traits, for which an arbitrary statistical threshold is defined. However, the correlation between the statistical significance of genetic variants and their “true” functional effects is largely unexplored. To this aim, we exploited a high-throughput automated phenotyping platform for the analysis of quantitative (morphological and behavioral) traits in the pupal stage of Drosophila melanogaster. Additionally, taking advantage of the ease of genetic mutagenesis in Drosophila melanogaster, we are capable to quantify the phenotypic effects at the single-gene level, in comparison to their statistical significance from GWA analysis.

Related publication:

  1. Wenyu Zhang, Guy Reeves, and Diethard Tautz(#). Identification of a genetic network for an ecologically relevant behavioral phenotype in Drosophila melanogaster. Mol Ecol. 2020 Feb;29(3):502-518. doi: 10.1111/mec.15341. [Link]
  2. Wenyu Zhang, Guy Reeves, and Diethard Tautz(#). Testing implications of the omnigenic model for the genetic analysis of loci identified through genome-wide association. Current Biology. 2021 Mar 08;31(5):1092-1098.e6. doi: 10.1016/j.cub.2020.12.023. [Link]

As a graduate student and a lecturer (2010.09 – 2016.10)

  • Evolution of orphan genes and de novo genes in Caenorhabditis elegans

Orphan genes are genes without detectable homologs in other lineages. As a special type of orphan genes, de novo genes are genes that de novo originated from non-coding DNA sequences. Compared with duplication-based new genes, the origination and function mechanisms of orphan genes and de novo genes remain largely unexplored. Herein, through a comprehensive and systematic computational pipeline, we present the first systematic evidence on the evolution of orphan genes and de novo origin of genes in nematodes and their impacts on the functional and phenotypic evolution and thus could shed new light on our appreciation of the importance of these new genes.

Related publication:

  1. Wenyu Zhang, Yuanxiao Gao, Manyuan Long, and Bairong Shen(#). Origination and evolution of orphan genes and de novo genes in the genome of Caenorhabditis elegans. Sci China Life Sci. 2019Apr;62(4):579-593. doi: 10.1007/s11427-019-9482-0. [Link]

  • Evolution of gene interaction networks from the view of new gene origination

The origin of new genes with novel functions creates genetic and phenotypic diversity in organisms. To acquire functional roles, new genes must integrate into ancestral gene-gene interaction (GGI) networks. However, the mechanisms by which new genes are integrated into ancestral networks, and their evolutionary significance, are yet to be characterized. In this project, we presented a study investigating the rates and patterns of new gene-driven evolution of GGI networks in the human and mouse genomes. We examined the network topological and functional evolution of new genes that originated at various stages in the human and mouse lineages by constructing and analyzing different GGI datasets. Our data cast new conceptual insights into the evolution of genetic networks.

Related publication:

  1. Wenyu Zhang, Patrick Landback, Andrea R Gschwend, Bairong Shen(#), and Manyuan Long(#). New genes drive the evolution of gene interaction networks in the human and mouse genomes. Genome Biol. 2015 Oct 1;16:202. doi: 10.1186/s13059-015-0772-4. [Link]
  2. Jian Zu(#), Yuexi Gu, Yu Li, Chentong Li, Wenyu Zhang, Yong E. Zhang, UnJin Lee, Li Zhang, and Manyuan Long. Topological evolution of coexpression networks by new gene integration maintains the hierarchical and modular structures in human ancestors. Sci China Life Sci. 2019 Apr;62(4):594-608. doi: 10.1007/s11427-019-9483-6. [Link]

  • Computational discovery of miRNA biomarkers for cancer diagnosis

Abnormal miRNA function has been implicated in various human cancers, and thus altered miRNA expression could serve as a biomarker for cancer diagnosis and treatment. Previous studies have provided evidence of multiple-to-multiple relationships between miRNAs and their target genes. However, our in-depth analysis revealed the scale-free features of the human miRNA-mRNA interaction network and showed the distinctive topological features of existing cancer miRNA biomarkers from previously published studies. Based on these observations, we developed a novel cancer miRNA biomarker prediction framework and applied this approach to the discovery of miRNA biomarkers in several human cancers. 

Related publication:

  1. Wenyu Zhang(*), Jin Zang(*), Xinhua Jing, Zhandong Sun, Wenying Yan, Dongrong Yang, Feng Guo(#), and Bairong Shen(#).  Identification of candidate miRNA biomarkers from miRNA regulatory network with application to prostate cancer. J Transl Med. 2014 Mar 11;12:66. doi: 10.1186/1479-5876-12-66. [Link]
  2. Jin Zhu(*), Sugui Wang(*), Wenyu Zhang(*), Junyi Qiu, Yuxi Shan, Dongrong Yang(#), and Bairong Shen(#). Screening key microRNAs for castration-resistant prostate cancer based on miRNA/mRNA functional synergistic network. Oncotarget. 2015 Dec 22; 6(41):43819-30. doi: 10.18632/oncotarget.6102. [Link]
  3. Jiajia Chen, Daqing Zhang, Wenyu Zhang, Yifei Tang, Wenying Yan, Lingchuan Guo, and Bairong Shen(#). Clear cell renal cell carcinoma associated microRNA expression signatures identified by an integrated bioinformatics analysis. J Transl Med. 2013 Jul 10;11:169. doi: 10.1186/1479-5876-11-169. [Link]
  4. Wenying Yan, Lihua Xu, Zhandong Sun, Yuxin Lin, Wenyu Zhang, Jiajia Chen, Shaoyan Hu, and Bairong Shen(#). MicroRNA biomarker identification for pediatric acute myeloid leukemia based on a novel bioinformatics model. Oncotarget. 2015 Sep 22;6(28):26424-36. doi: 10.18632/oncotarget.4459. [Link]
  5. Wenyu Zhang and Bairong Shen (2013). Chapter 8: Identification of Cancer MicroRNA Biomarkers Based on miRNA–mRNA Network. Bioinformatics for Diagnosis, Prognosis and Treatment of Complex Diseases. Translational Bioinformatics Volume 4. Springer, Dordrecht. [Link]
  6. Yuxin Lin, Zhandong Sun, Wenyu Zhang, Wenying Yan, Jiajia Chen, and Bairong Shen. (2015). Chapter 1: Proceedings on the bioinformatics studies of microRNA biomarkers. Annual Reviews on new biology 2015. (In Chinese). SCIENCE PRESS. [Link]

As an undergraduate student (2006.09 – 2010.06)

  • Practical evaluation of the next-generation sequencing data analysis tools

The fast development of next-generation sequencing technologies is accompanied by the development of many whole-genome sequence analysis methods and software, especially for de novo fragment assembly and short read alignment processes. Due to the poor knowledge about the applicability and performance of these software tools, choosing a befitting one becomes a tough task. In this project, we firstly systematically reviewed existing analysis tools on the de novo assembly and alignment and then compared the performance of these tools with both simulated datasets and real datasets from various sequencing platforms. Our comparison studies could assist researchers in selecting well-suited analysis tools and offer essential information for the improvement of existing methods or the development of novel analysis tools.

Related publication:

  1. Wenyu Zhang, Jiajia Chen, Yang Yang, Yifei Tang, Jing Shang, and Bairong Shen(#). A practical comparison of de novo genome assembly software tools for next-generation sequencing technologies. PLoS One. 2011 Mar 14;6(3):e17915. doi: 10.1371/ journal.pone.0017915. [Link]
  2. Jing Shang, Fei Zhu, Wanwipa Vongsangnak, Yifei Tang, Wenyu Zhang, and Bairong Shen(#). Evaluation and comparison of multiple aligners for next-generation sequencing data analysis. Biomed Res Int. 2014:309650. doi: 10.1155/2014/309650.  [Link]
  3. Wenyu Zhang (2017). Chapter 5: Short reads assembly; Chapter 10: Single-cell sequencing data analysis. Bioinformatics for Deep Sequencing Data with Examples. (In Chinese). SCIENCE PRESS. [Link to the book] [Link to the examples]
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