个人简介

       现任中山大学医学院教授，博士生导师。Genome Biology and Evolution副主编，Frontiers in Molecular Biosciences编委，国际计算生物学学会中国理事。在中山大学生命科学学院，于2006本科毕业，2011年获得博士学位。2011年至2015年在美国密歇根大学张建之教授实验室，从事博士后研究工作。2015年底获聘中山大学“百人计划”引进人才，并于2016年初入选国家高层次引进人才青年项目，2022年获得优秀青年科学基金项目资助。
       目前以第一作者或通讯作者的身份发表具有高影响力的学术论文多篇，分别刊登在Science、Nature Genetics、Lancet Microbe、Nat.Ecol.Evol.(2篇）、Nature Communications、Genome Biology、Mol. Biol. Evol（8篇）、PNAS、Cell Systems等国际知名杂志。
       本课题组以深度突变扫描（DMS）耦合多组学分析为高通量“突变-表型”引擎，贯通经典遗传学与群体遗传学，系统量化“突变→表达扰动→适应度效应→演化轨迹”全链参数，构建可检索、可预测的数字化景观。研究核心在于将功能基因组学的描述性知识转化为可计算方程，为临床意义未明变异（VUS）判读、肿瘤早筛及个体化用药提供实验范式，实现从基础发现到精准医学的全程跃迁。

学术成果 

1. 表达量-突变结局定则
   课题组基于自主构建的“表达梯度”深度突变扫描数据集，提出“表达-命运”模型：突变的有害程度可由其所在基因的表达水平线性调节。借助 CRISPRa/i 或合成启动子，将原本致死的突变精准下调至“安全表达窗口”，即可把高耗表型转化为低耗表型，显著延长突变在群体中的存续时间，为二次补偿或新功能化提供进化窗口。该框架不仅解释了高表达基因在定向选择下为何极度保守，还为罕见病的“低表达-低毒性”基因治疗提供了可量化的设计依据。
2. 位置效应外部性评分
   本课题组通过对 500 个不同染色体位点报告基因的系统整合，提出“位置外部性”概念：外源 DNA 片段的插入并非被动接受局部染色质环境的调控，而是主动参与转录资源竞争，重塑邻近基因的表达网络，并对宿主表型产生可量化的连锁效应。在此基础上构建的“位置外部性评分”可在单碱基分辨率下量化非编码区致病变异对局部调控网络的扰动强度。该指标对平衡易位、复杂重排及病毒插入等结构变异尤为敏感，实现了从“位置可疑”到“功能可评”的研究范式转化，为大规模疾病筛查提供了可扩展、可量化的分析框架。
3. X 染色体不敏感性模型
   本课题组整合跨平台单细胞 RNA-seq 图谱，首次发现 X 染色体具备“噪声容忍”的普适特性，提出“X 染色体不敏感模型”。X 染色体剂量敏感基因密度较常染色体低约 30%，可显著缓解单拷贝表达不足；X 连锁基因允许 10–15% 的表达波动而无适应性代价，无需单细胞级完美剂量补偿即可缓冲 X:AA 失衡。基于该模型可构建“噪声容忍度评分”，将 X 连锁候选变异按功能影响分层，降低罕见病筛查假阳性率，为 X 连锁疾病的精准、可扩展量化筛查提供进化依据与算法框架。
4. 多效性“快速修剪”定律
   本课题整合 100 余个转录因子的表型图谱与逾百万份 QTL 群体基因组数据，发现基因多效性与QTL的年龄呈显著负相关。高多效位点因正负效应交织，在任意环境波动下均暴露净适应代价，受负选择快速清除；低多效位点则因代价微弱而长期维持多态。据此提出“快速修剪律”：自然选择持续剔除高代价调控变异，驱动调控网络向低耦合-高内聚的模块化结构收敛，为复杂性状及多基因疾病的适应性演化提供可遗传的调控架构。

学术论著

37. Zheng B, Zhang W, Yu G, Shi W, Deng S, Zhang X, Chen J, Zhou Z, Shan Y, Wu W, Long E, Chen X#, Yang JR#. Translational fidelity and longevity are genetically linked. Nat Commun. 2025 Aug.
36. Zhang X, Li Z, Chen J, Yang W, He X, Wu P, Chen F, Zhou Z, Ren C, Shan Y, Wen X, Lyubetsky VA, Rusin LY, Chen X, Yang JR#. Stereotyped Subclones Revealed by High-Density Single-Cell Lineage Tracing Support Robust Development. ADV SCI. 2025 Apr.
35. Chen J, Chen X#. Human single-cell RNA-sequencing data supports the hypothesis of X chromosome insensitivity but is ineffective in testing the dosage compensation model, Mol. Biol. Evol. 2025 Feb. 
34. Liu L, Liu Y, Min L, Zhou Z, He X, Xie Y, Cao W, Deng S, Lin X#, He X#, Chen X#. Most pleiotropic effects of gene knockouts are evolutionarily transient in yeasts. Mol. Biol. Evol. 2024 Sep.
33. Chen J, Chen X#. Dosage compensation of sex chromosomes in animals. Hereditas(Beijing). 2024 Aug. 
32. Guo Z, Feng S, Liang L, Wu Z, Min L, Wang R, Li J, Zhong LL, Zhao H, Chen X#, Tian GB#, Yang JR#. Assessment of the reversibility of resistance in the absence of antibiotics and its relationship with the resistance gene's fitness cost: a genetic study with mcr-1. Lancet Microbe. 2024 Aug.
31. Yu G, Liu Y, Li Z, Deng S, Wu Z, Zhang X, Chen W, Yang J, Chen X, Yang JR#. Genome-wide probing of eukaryotic nascent rna structure elucidates cotranscriptional folding and its antimutagenic effect. Nat Commun. 2023 Sep.
30. Wang D, Li Z, Huang W, Cao S, Xie L, Chen Y, Li H, Wang L, Chen X#, Yang JR#. Single-cell transcriptomics reveals heterogeneity and intercellular crosstalk in human intervertebral disc degeneration. iScience. 2023 Apr.
29. Chen F, Li Z, Zhang X, Wu P, Yang W, Yang J, Chen X, Yang JR#. Phylogenetic comparative analysis of single-cell transcriptomes reveals constrained accumulation of gene expression heterogeneity during clonal expansion. Mol. Biol. Evol. 2023 May.
28. Feng S, Wu Z, Liang W, Zhang X, Cai X, Li J, Liang L, Lin D, Stoesser N, Doi Y, Zhong LL, Liu Y, Xia Y, Dai M, Zhang L, Chen X#, Yang JR#, Tian GB#. Prediction of antibiotic resistance evolution by growth measurement of all proximal mutants of beta-lactamase. Mol. Biol. Evol. 2022 May.
27. Wu Z, Cai X, Zhang X, Liu Y, Tian GB, Yang JR, Chen X#. Expression level is a major modifier of the fitness landscape of a protein coding gene. Nat Ecol Evol. 2022 Jan.
26. Gui Q*，Deng S*，Zhou Z，Cai W，Zhang X，Shi W，Cai X，Jiang W, Cui Z, Hu Z# and Chen X#. Transcriptome Analysis in Yeast Reveals the Externality of Position Effects. Mol. Biol. Evol. 2021 Apr.
25. Yu G, Zhu H, Chen X# and Yang JR#. Specificity of RNA Folding and its Association with Evolutionarily Adaptive mRNA Secondary Structures. Genom Proteom Bioinf. 2021 Feb.
24. Mo N, Zhang X, Shi W, Yu G, Chen X# and Yang J#. Bidirectional genetic control of phenotypic heterogeneity and its implication for cancer drug resistance. Mol Biol Evol. 2020 Dec.
23. Chen J, Wang M, He X, Yang J# and Chen X#. The Evolution of Sex Chromosome Dosage Compensation in Animals. J Genet Genomics. 2020 Nov.
22. Yuan M, Yang X, Lin J, Cao X, Chen F, Zhang X, Li Z, Zheng G, Wang X, Chen X# and Yang J#. Alignment of Cell Lineage Trees Elucidates Genetic Programs for the Development and Evolution of Cell Types. iScience. 2020 Jul.
21. Liu L, Wang Y, Zhang D, Chen Z, Chen X, Su Z and He X. The Origin of additive genetic variance driven by positive selection. Mol Biol Evol. 2020 Apr.
20. Chen F, Wu P, Deng S, Zhang H, Hou Y, Hu Z, Zhang J#, Chen X# and Yang JR#. Dissimilation of synonymous codon usage bias in virus-host coevolution due to translational selection. Nat Ecol Evol. 2020 Mar.
19. Yang JR# and Chen X#. Dosage sensitivity of X-linked genes in human embryonic single cells. BMC genomics. 2019 Jan.
18. Duan C*, Huan Q*, Chen X*, Wu S, Carey LB, He X and Qian W. Reduced intrinsic DNA curvature leads to increased mutation rate. Genome Biol. 2018 Sep. (*Co-first authors)
17. Chen X, Zhang J. The X to autosome expression ratio in haploid and diploid human embryonic stem cells. Mol Biol Evol. 2016 Sep.
16. Chen X, Zhang J. The genomic landscape of position effects on protein expression level and noise in yeast. Cell Syst. 2016 May.
15. Chen X, Yang JR, Zhang J. Nascent RNA folding mitigates transcription associated mutagenesis. Genome Res. 2015 Oct.
14. Chen X, Zhang J. No X-chromosome dosage compensation in human proteomes. Mol Biol Evol. 2015 Feb.
13. Chen X, Zhang J. Mutation accumulation experiment supports elevated mutation rates at highly transcribed sites. (Letter to Editor) PNAS. 2014 Sep.
12. Yang JR, Chen X, Zhang J. Codon-by-codon modulation of translational speed and accuracy via mRNA folding. PLoS Biol. 2014 Jul.
11. Chen X, Zhang J. Why Are Genes Encoded on the Lagging Strand of the Bacterial Genome? Genome Biol Evol. 2013 Nov.
10. Chen X, Zhang J. No Gene-Specific Optimization of Mutation Rate in Escherichia coli. Mol Biol Evol. 2013 Mar.
9. Park C, Chen X, Yang JR, Zhang J. Differential requirements for mRNA folding partially explain why highly expressed proteins evolve slowly. PNAS. 2013 Feb.
8. Chen X, Zhang J. The ortholog conjecture is untestable by the current Gene Ontology but is supported by RNA sequencing data. PLoS Comput Biol. 2012 Nov.
7. Chen X, Chen Z, Chen H, Su Z, Yang J, Shi S, He X. Nucleosomes suppress spontaneous mutations base-specifically in eukaryotes. Science. 2012 Mar.
6. He X, Chen X, Xiong Y, Chen Z, Wang X, Shi S, Wang X, Zhang J. He et al. reply. Nat Genet. 2011 Nov.
5. Yang G, Zhou R, Tang T, Chen X, Ouyang J, He L, Li W, Chen S, Guo M, Li X, Zhong C, Shi S. Gene expression profiles in response to salt stress in Hibiscus tiliaceus. Plant Mol Biol Rep. 2011 Sep.
4. Yang G, Chen X, Tang T, Zhou R, Chen S, Li W, Ouyang J , He L, Shi S. Comparative genomics of two ecologically differential populations of Hibiscus tiliaceus under salt stress. Funct Plant Biol. 2011 Mar.
3. Xiong Y*, Chen X*, Chen Z, Wang X, Shi S, Wang X, Zhang J, He X. RNA sequencing shows no dosage compensation of the active X-chromosome. Nat Genet. 2010 Dec. (*Co-first authors)
2. Chen X, Shi S, He X. Evidence for gene length as a determinant of gene coexpression in protein complexes. Genetics. 2009 Oct.
1. Zhou R, Zeng K, Wu W, Chen X, Yang Z, Shi S, Wu CI. Population genetics of speciation in nonmodel organisms: I. Ancestral polymorphism in mangroves. Mol Biol Evol. 2007 Dec.

获奖荣誉

国家重点研发计划《组织干细胞突变的形成和演化规律研究》项目，子课题负责人（课题经费678万）

中山大学引进人才项目，项目负责人（项目经费300万）

国家高层次引进人才青年项目，项目负责人（项目经费300万）

国家优秀青年科学基金项目（项目经费200万）

国家自然科学基金面上项目，项目负责人（2项，项目经费60万和58万）

国家高层次引进人才青年项目广东省配套经费，项目负责人（项目经费50万）

本实验室长期招收具有基础医学或生物学背景的硕士生、博士生、博士后、助理研究员以及研究员。

欢迎有志于遗传学研究的同学和同行加入！