研究方向：陆剑：
北京大学生命科学学院教授、博士生导师，Science Bulletin和Molecular Biology and Evolution（MBE）编委（Associate Editor）。本实验室的研究方向主要是分子进化和基因组学。
生物的表型进化不仅可以通过改变基因功能，还可以通过基因表达模式变化而实现。由于自然选择的不完美性以及生存环境不断变化，生物进化过程常伴随着从基因型到表型多个层次的不断修补。然而当前对进化修补过程的分子基础及自然选择在此过程中的作用机理却缺乏深入了解。本实验室长期致力于群体遗传学、进化基因组学和基因表达调控等领域的研究，近五年以（共同）通讯作者身份在Molecular Biology and Evolution、National Science Review和Nature Communications等期刊发表论文25篇，多维度解析基因表达调控的进化机制和基因组进化规律，建立了功能与进化规律的关联。当前本实验室紧密结合进化与功能基因组学方法，从三个层面探索生物基因组和表型适应性演化的机制和规律：
1. 蛋白质合成调控的演化机制和规律。结合分子演化和基因学方法多维度探索上游开放读码框（uORF）、非编码小RNA和RNA编辑这三类元件/因子在蛋白质翻译调控中的功能和序列进化规律，探索翻译调控与疾病的关联。
2. 以果蝇为模式解析环境适应的遗传和进化机制。本实验从中国不同地区采集了10000多个果蝇品系，通过基因组测序和表型相关分析，探索果蝇适应复杂自然环境的遗传架构以及蝇环境适应中自然选择作用的靶点及机制。
3. 新冠病毒的分子演化和全球动态研究。本实验室通过新冠病毒基因组的分子演化研究，与合作者率先发现新冠病毒存在“L”和“S”两个主要谱系，建立了完善的亚谱系命名规则并揭示了变异的演进规律，探索新冠病毒分子演化动态及驱动因素。相关研究获得科技部等有关部门表彰。
代表性科研论文：
1. Tang X, Qian Z, Lu X, Lu J* (2023) Adaptive evolution of the Spike protein in coronaviruses. Molecular Biology and Evolution. msad089.
2. Qian Z*, Li P, Tang X, Lu J* (2022) Evolutionary dynamics of the severe acute respiratory syndrome coronavirus 2 genomes. Medical Review. DOI: 10.1515/mr-2021-0035 .
3. Ruan Y#, Hou M#, Tang X#, He X, Lu X, Lu J*, Wu CI*, Wen H* (2022) The runaway evolution of SARS-CoV-2 leading to the highly evolved Delta strain. Molecular Biology and Evolution. msac046. DOI: 10.1093/molbev/msac046 .
4. Sun Q#, Shu C#, Shi W, Luo Y, Fan G, Nie J, Bi Yu, Wang Q, Qi J, Lu J, Zhou Y, Shen Z, Meng Z, Zhang X, Yu Z, Gao S*, Wu L*, Ma J*, Hu S* (2022) VarEPS: an evaluation and prewarning system of known and virtual variations of SARS-CoV-2 genomes. Nucleic Acids Research. 50(D1): D888–D897. DOI: 10.1093/nar/gkab921 .
5. Duan Y, Tang X, Lu J* (2022) Evolutionary driving forces of A-to-I editing in metazoans. WIREs RNA. 13：e1666.
6. Zhang H, Wang Y, Wu X, Tang X, Wu C, Lu J* (2021) Determinants of genome-wide distribution and evolution of uORFs in eukaryotes. Nature Communications. 12: 1076.
7. Zhang H#, Wang Y#, Tang X, Dou S, Sun Y, Zhang Q, Lu J* (2021) Combinatorial regulation of gene expression by uORFs and microRNAs in Drosophila. Science Bulletin. 66(3): 225–228.
8. Duan Y, Dou S, Porath HT, Huang J, Eisenberg E*, Lu J* (2021) A-to-I RNA editing in honeybees shows signals of adaptation and convergent evolution. iScience 24(1): 101983.
9. Ruan Y, Luo Z, Tang X, Li G, Wen H, He X, Lu X*, Lu J*, Wu CI* (2021) On the founder effect in COVID-19 outbreaks: how many infected travelers may have started them all?. National Science Review 8(1): nwaa246.
10. Tang X#, Ying R#, Yao X#, Li G, Wu C, Tang Y, Li Z, Kuang B, Wu F, Chi C, Du X, Qin Y, Gao S, Hu S, Ma J, Liu T, Pang X, Wang J, Zhao G, Tan W*, Zhang Y*, Lu X*, Lu J* (2021) Evolutionary analysis and lineage designation of SARS-CoV-2 genomes. Science Bulletin. 66(22): 2297-2311.
11. Hu B#, Liu R#, Tang X#, Pan Y#, Wang M#, Tong Y#, Ye G#, Shen G#, Ying R#, Fu A, Li D, Zhao W, Peng J, Guo J, Men D, Yao X, Wang Y, Zhang H, Feng Z, Yu J, Chen L, Deng Z, Lu X, Zhang YP*, Li Y*, Liu B*, Yu L*, Li Y*, Lu J*, Liu T* (2021) The concordance between the evolutionary trend and the clinical manifestation of the two SARS-CoV-2 variants. National Science Review 8(8): nwab073.
12. Wu CI*, Wen H, Lu J, Su X, Hughes AC, Zhai W, Chen C, Chen H, Li M, Song S, Qian Z, Wang Q, Chen B, Guo Z, Ruan Y, Lu X, Wei F, Jin L, Kang L, Xue Y, Zhao G, Zhang YP (2021) On the origin of SARS-CoV-2—The blind watchmaker argument. Science China Life Sciences 64: 1560–1563.
13. Wu Z, Jin Q, Wu G, Lu J, Li M, Guo D, Lan K, Feng L, Qian Z, Ren L, Tan W, Xu W, Yang W, Wang J*, Wang C (2021) SARS-CoV-2's origin should be investigated worldwide for pandemic prevention. The Lancet 398(10308): 1299-1303.
14. Sun Q, Shu C, Shi W, Luo Y, Fan G, Nie J, Bi Yu, Wang Q, Qi J, Lu J, Zhou Y, Shen Z, Meng Z, Zhang X, Yu Z, Gao S*, Wu L*, Ma J*, Hu S* (2021) VarEPS: an evaluation and prewarning system of known and virtual variations of SARS-CoV-2 genomes. Nucleic Acids Research gkab921.
15. Peng MS#*, Li JB#, Cai ZF#, Liu H#, Tang X#, Ying R, Zhang JN, Tao JJ, Yin TT, Zhang T, Hu JY, Wu RN, Zhou ZY, Zhang ZG, Yu L, Yao YG, Shi ZL, Lu XM, Lu J*, Zhang YP* (2021) The high diversity of SARS-CoV-2-related coronaviruses in pangolins alerts potential ecological risks. Zoological Research. 42(6): 833–843.
16. Yu T, Huang X, Dou S, Tang X, Luo S, Theurkauf WE*, Lu J*, Weng Z* (2021) A benchmark and an algorithm for detecting germline transposon insertions and measuring de novo transposon insertion frequencies. Nucleic Acids Research 49(8): e44.
17. Feng Y#, Xu H#, Liu J#, Xie N, Gao L, He Y, Yao Y, Lv F, Zhang Y, Lu J, Zhang W, Li CY, Hu X*, Yang Z*, Xiao RP (2021) Functional and adaptive significance of promoter mutations that affect divergent myocardial expressions of TRIM72 in primates. Molecular Biology and Evolution. 38(7): 2930–2945.
14. Tang X#, Wu C#, Li X#, Song Y#, Yao X, Wu X, Duan Y, Zhang H, Wang Y, Qian Z, Cui J*, Lu J* (2020) On the origin and continuing evolution of SARS-CoV-2. National Science Review. 7(6): 1012–1023.
15. Li T#, Tang X#, Wu C, Yao X, Wang Y, Lu X*, Lu J* (2020) The use of SARS-CoV-2-related coronaviruses from bats and pangolins to polarize mutations in SARS-Cov-2. Science China Life Sciences. 63(10): 1608-1611.
16. Luo S#, Zhang H#, Duan Y#, Yao X, Clark AG*, Lu J* (2020) The Evolutionary Arms Race between Transposable Elements and piRNAs in Drosophila melanogaster. BMC Evolutionary Biology. 20: 14.
17. Wang Y#, Zhang H#, Lu J* (2020). Recent advances in ribosome profiling for deciphering translational regulation. Methods 176: 46–54 (Invited Review, 被Faculty of 1000推荐).
18. Zhang H#, Wang Y#, Lu J* (2019). Function and evolution of upstream ORFs in eukaryotes. Trends in Biochemical Sciences 44(9): 782-794 (Invited Review).
19. Dou S#, Wang Y#, Lu J* (2019). Metazoan tsRNAs: biogenesis, evolution and regulatory functions. Non-Coding RNA 5(1): 18 (Invited Review).
20. Wu C, Lu J* (2019). Diversification of transposable elements in arthropods and its impact on genome evolution. Genes 10(5).
21. Zhang H#, Wang Y#, Li J, Chen H, He X, Zhang H, Liang H*, Lu J* (2018). Biosynthetic energy cost for amino acids decreases in cancer evolution. Nature Communications 9(1): 4124.
22. Zhang H#, Dou S#, He F, Luo J, Wei L, and Lu J* (2018). Genome-wide maps of ribosomal occupancy provide insights into adaptive evolution and regulatory roles of uORFs during Drosophila development. PLOS Biology 16(7): e2003903.
23. Luo S#, He F#, Luo J#, Dou S#, Wang Y#, Guo A, Lu J* (2018). Drosophila tsRNAs preferentially suppress general translation machinery via antisense pairing and participate in cellular starvation response. Nucleic Acids Research 46(10): 5250–5268.
24. Luo J#, Wang Y#, Yuan J#, Zhao Z, Lu J* (2018). MicroRNA duplication accelerates the recruitment of new targets during vertebrate evolution. RNA 24(6): 787–802.
25. Duan Y#, Dou S#, Zhang H#, Wu C, Wu M, Lu J* (2018). Linkage of A-to-I RNA editing in metazoans and the impact on genome evolution. Molecular Biology and Evolution 35(1): 132–148.
26. Duan Y#, Dou S#, Luo S#, Zhang H, Lu J* (2017). Adaptation of A-to-I RNA editing in Drosophila. PLOS Genetics 13(3): e1006648.
27. Luo S, Lu J* (2017). Silencing of transposable elements by piRNAs in Drosophila: an evolutionary perspective. Genomics, Proteomics & Bioinformatics 15(3): 164–176.
28. Wang Y, Luo J, Zhang H, and Lu J* (2016). MicroRNAs in the same clusters evolve to coordinately regulate functionally related genes. Molecular Biology and Evolution 33(9): 2232–2247; author reply in 10.1093/molbev/msz121.
29. Yin S, Fan Y, Zhang H, Zhao Z, Hao Y, Li J, Sun C, Yang J, Yang Z, Yang X, Lu J, Xi JJ*. (2016). Differential TGFβ pathway targeting by miR-122 in humans and mice affects liver cancer metastasis. Nature Communications 7: 11012.
30. Zhang XY, Zhu Y, Liu XD, Hong XY, Xu Y, Zhu P, Shen Y, Ji YS, Wen X, Zhang C, Zhao Q, Wang YC, Lu J, Guo HW*. (2015). Suppression of endogenous gene silencing by degradation of normal cytoplasmic RNA in Arabidopsis. Science 348(6230): 120–123.
31. Yu FL#, Lu J#, Liu XM#, Gazave E, Chang D, Raj S, Hunter-Zinck H, Blekhman R, Arbiza L, Hout C, Morrison A, Johnson AD, Bis J, Cupples LA, Psaty BM, Muzny D, Yu J, Gibbs RA, Keinan A, Clark G, Boerwinkle E* (2015). Population genomics analyses of 962 whole genomes of humans reveal natural selection in non-coding regions. PLOS One 10(3): e0121644.
32. Ye KX, Lu J, Ma F, Keinan A, Gu ZL* (2014). Extensive Pathogenicity of Mitochondrial Heteroplasmy in Healthy Human Individuals. Proceedings of the National Academy of Sciences of the United States of America 111(29): 10654–10659.
33. Ye KX*, Lu J, Raj SM, Gu ZL* (2013). Human expression QTLs are enriched in signals of environmental adaptation. Genome Biology and Evolution 5(9): 1689–1701.
34. Lu J*, Clark AG* (2012). Impact of microRNA regulation on variation in human gene expression. Genome Research 22(7): 1243–1254.
35. Zhou RC#, Ling SP#, Zhao WM#, Osada N, Chen SF, Zhang M, He ZW, Bao H, Zhong CR, Zhang B, Lu XM, Turissini D, Duke NC, Lu J*, Shi SH*, Wu CI* (2011). Population genetics in non-model organisms: II. Natural selection in marginal habitats revealed by deep sequencing on dual platforms. Molecular Biology and Evolution 28(10): 2833–2842.
36. Tang T#, Kumar S#, Shen Y, Lu J, Wu ML, Shi S, Li WH, Wu CI* (2010). Adverse interactions between micro-RNAs and target genes from different species. Proceedings of the National Academy of Sciences of the United States of America 107: 12935–-12940.
37. Lu J, Clark AG* (2010). Population dynamics of PIWI-interacting RNAs (piRNAs) and their targets in Drosophila. Genome Research 20: 212–227.
38. Lu J, Shen Y,Wu QF, Kumar S, He B, Carthew RW, Wang SM*, Wu CI* (2008). The birth and death of microRNA genes in Drosophila. Nature Genetics 40: 351–355; author reply in 42: 9–10.
39. Lu J, Fu Y, Kumar S, Shen Y, Zeng K, Xu A, Carthew RW, Wu CI* (2008). Adaptive evolution of newly emerged micro-RNA genes in Drosophila. Molecular Biology and Evolution 25: 929–938.
40. Wang HY, Fu Y, McPeek MS, Lu X, Nuzhdin S, Xu A, Lu J, Wu ML, Wu CI* (2008). Complex genetic interactions underlying expression differences between Drosophila races: analysis of chromosome substitutions. Proceedings of the National Academy of Sciences of the United States of America 105: 6362–6367.
41. Wu QF, Kim YC, Lu J, Xuan ZY, Chen J, Zheng YL, Zhou T, Zhang MQ, Wu CI, Wang SM* (2008). Poly A- transcripts expressed in HeLa cells. PLOS ONE 3(7): e2803.
42. Clark AG, Eisen MB, Smith DR, Bergman CM, Oliver B, Markow TA et al (2007). Evolution of genes and genomes on the Drosophila phylogeny. Nature 450: 203–218 (Lu J is a coauthor of this paper).
43. Shapiro JA, Huang W, Zhang C, Hubisz MJ, Lu J, Turissini DA, Fang S, Wang HY, Hudson RR, Nielsen R, Chen Z, Wu CI* (2007). Adaptive genic evolution in the Drosophila genomes. Proceedings of the National Academy of Sciences of the United States of America 104: 2271–2276.
44. Lu J#, Tang T#, Tang H, Huang JZ, Shi SH*, Wu CI* (2006). The accumulation of deleterious mutations in rice genomes: a hypothesis on the cost of domestication. Trends in Genetics 22: 126–131.
45. Tang T#, Lu J#, Huang J, He J, McCouch SR, Purugganan MD, Shi SH*, Wu CI* (2006). Genomic variation in rice - Genesis of highly polymorphic linkage blocks during domestication. PLOS Genetics 2(11): e199.
46. Lu J, Wu CI* (2005). Weak selection revealed by the whole-genome comparison of the X chromosome and autosomes of human and chimpanzee. Proceedings of the National Academy of Sciences of the United States of America 102: 4063–4067.
47. Tang H, Wyckoff GJ, Lu J, Wu CI* (2004). A universal evolutionary index for amino acid changes. Molecular Biology and Evolution 21: 1548–1556.
48. Lu J, Li WH, Wu CI* (2003). Comment on "Chromosomal speciation and molecular divergence-accelerated evolution in rearranged chromosomes". Science 302: 988.
49. Lu J, Lü J, Chen HX, Zhang WX, Dai ZH* (2002). Molecular phylogeny of Drosophila auraria species complex (in Chinese). Acta Genetica Sinica 29: 39–49.
50. Zhao Z, Lu J, Dai ZH* (2001). Genetic differentiation within Drosophila auraria species complex revealed by Random Amplified Polymorphic DNA (RAPD) (in Chinese). Acta Zoologica Sinica 47: 625–631.
