果蝇转座子的特性、调控及其在基因组进化中的作用

doi:10.12300/j.issn.1674-5817.2025-112

摘要/Abstract

摘要：

转座子（transposable elements，TEs）是基因组中可移动的DNA序列，在物种演化、基因组稳定性及基因调控中扮演关键角色。果蝇（Drosophila melanogaster）作为经典模式动物，其基因组中TEs占比约20%，是研究TEs的生物学特性、宿主防御机制及功能演化的理想模型，也为理解高等生物乃至人类TEs相关疾病的机制提供了重要范式。本文系统阐述了果蝇中TEs的分类、分布特征及其与宿主基因组的动态互作，重点探讨了以piRNA（Piwi-interacting RNA）通路为核心的宿主防御系统；详细解析了果蝇中关键TEs家族（如Gypsy、Copia、P-element、I-element）的生物学特性及其在基因组进化中的双重作用：一方面，TEs插入可引发基因组不稳定、杂种不育及衰老表型，为研究相关人类疾病（如神经退行性疾病、基因组不稳定综合征等）提供了模型基础；另一方面，其序列可被宿主驯化（co-option）为新型调控元件或功能基因，驱动适应性创新；展望了未来研究方向，包括环境应激对TEs活性的调控、piRNA通路与其他小RNA系统的交互，以及TEs在衰老和神经退行性疾病中的分子机制。果蝇TEs的研究不仅深化了人们对TEs生物学的理解，其揭示的保守机制和原理，为利用实验动物模型研究人类疾病、开发基因治疗和基因编辑技术提供了关键理论基础和重要启示。

关键词: 果蝇, 转座子, piRNA, 功能演化, 宿主互作

Abstract:

Transposable elements (TEs) are mobile DNA sequences in genomes that play key roles in species evolution, genome stability, and gene regulation. Drosophila melanogaster is a classic model animal with about 20% transposons in its genome, which makes it an ideal model for studying the biological properties, host defense mechanisms, and functional evolution of TEs. Its discovery provides an important paradigm for understanding the relevant mechanisms in higher organisms and even in humans. This review systematically elucidates the classification and distribution characteristics of transposons in D. melanogaster and their interactions with the host genome, mainly focused on discussing the host defense system centered on the Piwi-interacting RNA (piRNA) pathway. Additionally, we analyze the biological properties of key transposon families (e.g., Gypsy, Copia, P-element and I-element) in Drosophila, as well as their dual roles in genome evolution. On the one hand, transposon insertions have been demonstrated to trigger genomic instability, heterozygous sterility and aging phenotypes, thus providing a suitable model basis for the study of related human diseases (e.g., neurodegenerative diseases, genomic instability syndromes, etc. ). On the other hand, their sequences can be co-opted by the host to create novel regulatory elements or functional genes, thereby driving adaptive innovation. Finally, we discuss future research directions, including the regulation of transposon activity by environmental stress, the interaction of the piRNA pathway with other small RNA systems, and the molecular mechanisms of transposons in aging and neurodegenerative diseases. The study of Drosophila transposons has been demonstrated to facilitate a more profound comprehension of transposon biology, whilst concomitantly unveiling conserved mechanisms and principles that provide a theoretical foundation and significant insights into the study of human diseases utilising experimental animal models. Furthermore, these insights are instrumental in the development of gene therapy and gene editing technologies.

Key words: Drosophila, Transposons, piRNA, Functional evolution, Host interactions

王也,王露.果蝇转座子的特性、调控及其在基因组进化中的作用[J]. 实验动物与比较医学.. DOI: 10.12300/j.issn.1674-5817.2025-112.

WANG Ye,WANG Lu. Drosophila Transposons: Characterization, Regulation and Their Role in Genome Evolution[J]. Laboratory Animal and Comparative Medicine. DOI: 10.12300/j.issn.1674-5817.2025-112.

图/表 3

参考文献 77

[1]	B M. The Origin and Behavior of Mutable Loci in Maize [J]. PNAS, 1950, 36(6): 344–55.
[2]	WELLS J N, FESCHOTTE C. A Field Guide to Eukaryotic Transposable Elements [J]. Annu Rev Genet, 2020, 54: 539-61.
[3]	BHAT A, GHATAGE T, BHAN S, et al. Role of Transposable Elements in Genome Stability: Implications for Health and Disease [J]. Int J Mol Sci, 2022, 23(14).
[4]	LIANG Y, QU X, SHAH N M, et al. Towards targeting transposable elements for cancer therapy [J]. Nat Rev Cancer, 2024, 24(2): 123-40.
[5]	KAZAZIAN H H, JR., MORAN J V. Mobile DNA in Health and Disease [J]. N Engl J Med, 2017, 377(4): 361-70.
[6]	BIER E. Gene drives gaining speed [J]. Nat Rev Genet, 2022, 23(1): 5-22.
[7]	KLEIN S J, O'NEILL R J. Transposable elements: genome innovation, chromosome diversity, and centromere conflict [J]. Chromosome Res, 2018, 26(1-2): 5-23.
[8]	DRONGITIS D, ANIELLO F, FUCCI L, et al. Roles of Transposable Elements in the Different Layers of Gene Expression Regulation [J]. Int J Mol Sci, 2019, 20(22).
[9]	GASPAROTTO E, BURATTIN F V, DI GIOIA V, et al. Transposable Elements Co-Option in Genome Evolution and Gene Regulation [J]. Int J Mol Sci, 2023, 24(3).
[10]	NISHIHARA H. Transposable elements as genetic accelerators of evolution: contribution to genome size, gene regulatory network rewiring and morphological innovation [J]. Genes Genet Syst, 2020, 94(6): 269-81.
[11]	COSBY R L, CHANG N C, FESCHOTTE C. Host-transposon interactions: conflict, cooperation, and cooption [J]. Genes Dev, 2019, 33(17-18): 1098-116.
[12]	GORBUNOVA V, SELUANOV A, MITA P, et al. The role of retrotransposable elements in ageing and age-associated diseases [J]. Nature, 2021, 596(7870): 43-53.
[13]	SUN W, SAMIMI H, GAMEZ M, et al. Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies [J]. Nat Neurosci, 2018, 21(8): 1038-48.
[14]	DELLA VALLE F, REDDY P, AGUIRRE VAZQUEZ A, et al. Reactivation of retrotransposable elements is associated with environmental stress and ageing [J]. Nat Rev Genet, 2025.
[15]	LI W, PRAZAK L, CHATTERJEE N, et al. Activation of transposable elements during aging and neuronal decline in Drosophila [J]. Nat Neurosci, 2013, 16(5): 529-31.
[16]	SCHRADER L, SCHMITZ J. The impact of transposable elements in adaptive evolution [J]. Mol Ecol, 2019, 28(6): 1537-49.
[17]	HSU P S, YU S H, TSAI Y T, et al. More than causing (epi)genomic instability: emerging physiological implications of transposable element modulation [J]. J Biomed Sci, 2021, 28(1): 58.
[18]	GALBRAITH J D, HAYWARD A. The influence of transposable elements on animal colouration [J]. Trends Genet, 2023, 39(8): 624-38.
[19]	DOPKINS N, O'MARA M M, LAWRENCE E, et al. A field guide to endogenous retrovirus regulatory networks [J]. Mol Cell, 2022, 82(20): 3763-8.
[20]	CASOLA C, LAWING A M, BETRAN E, et al. PIF-like transposons are common in drosophila and have been repeatedly domesticated to generate new host genes [J]. Mol Biol Evol, 2007, 24(8): 1872-88.
[21]	BARRON M G, FISTON-LAVIER A S, PETROV D A, et al. Population genomics of transposable elements in Drosophila [J]. Annu Rev Genet, 2014, 48: 561-81.
[22]	RECH G E, RADIO S, GUIRAO-RICO S, et al. Population-scale long-read sequencing uncovers transposable elements associated with gene expression variation and adaptive signatures in Drosophila [J]. Nat Commun, 2022, 13(1): 1948.
[23]	SHEN D, XU Y, SHI Q, et al. Retrotransposon 3S18 forms self-protective aggregates and prolongs mid-oogenesis [J]. Cell Rep, 2025, 44(7): 115914.
[24]	WANG L, DOU K, MOON S, et al. Hijacking Oogenesis Enables Massive Propagation of LINE and Retroviral Transposons [J]. Cell, 2018, 174(5): 1082-94 e12.
[25]	MOON S, CASSANI M, LIN Y A, et al. A Robust Transposon-Endogenizing Response from Germline Stem Cells [J]. Dev Cell, 2018, 47(5): 660-71 e3.
[26]	YANG F, SU W, CHUNG O W, et al. Retrotransposons hijack alt-EJ for DNA replication and eccDNA biogenesis [J]. Nature, 2023, 620(7972): 218-25.
[27]	MÉREL V, BOULESTEIX M, FABLET M, et al. Transposable elements in Drosophila [J]. Mobile DNA, 2020, 11(1).
[28]	SPRADLING A C, RUBIN G M. Transposition of cloned P elements into Drosophila germ line chromosomes [J]. Science, 1982, 218(4570): 341-7.
[29]	RUBIN G M, SPRADLING A C. Genetic transformation of Drosophila with transposable element vectors [J]. Science, 1982, 218(4570): 348-53.
[30]	HO S, THEURKAUF W, RICE N. piRNA-Guided Transposon Silencing and Response to Stress in Drosophila Germline [J]. Viruses, 2024, 16(5).
[31]	CZECH B, MUNAFO M, CIABRELLI F, et al. piRNA-Guided Genome Defense: From Biogenesis to Silencing [J]. Annu Rev Genet, 2018, 52: 131-57.
[32]	WANG X, RAMAT A, SIMONELIG M, et al. Emerging roles and functional mechanisms of PIWI-interacting RNAs [J]. Nat Rev Mol Cell Biol, 2023, 24(2): 123-41.
[33]	LUO Y, HE P, KANRAR N, et al. Maternally inherited siRNAs initiate piRNA cluster formation [J]. Mol Cell, 2023, 83(21): 3835-51 e7.
[34]	LEE Y C G, KARPEN G H. Pervasive epigenetic effects of Drosophila euchromatic transposable elements impact their evolution [J]. Elife, 2017, 6.
[35]	LEE Y C. The Role of piRNA-Mediated Epigenetic Silencing in the Population Dynamics of Transposable Elements in Drosophila melanogaster [J]. PLoS Genet, 2015, 11(6): e1005269.
[36]	SELVARAJU D, WIERZBICKI F, KOFLER R. Experimentally evolving Drosophila erecta populations may fail to establish an effective piRNA-based host defense against invading P-elements [J]. Genome Res, 2024, 34(3): 410-25.
[37]	SATYAKI P R, CUYKENDALL T N, WEI K H, et al. The Hmr and Lhr hybrid incompatibility genes suppress a broad range of heterochromatic repeats [J]. PLoS Genet, 2014, 10(3): e1004240.
[38]	SHIBA T, SAIGO K. Retrovirus-like particles containing RNA homologous to the transposable element copia in Drosophila melanogaster [J]. Nature, 1983, 302(5904): 119-24.
[39]	TOURET F, GUIGUEN F, GREENLAND T, et al. In between: gypsy in Drosophila melanogaster reveals new insights into endogenous retrovirus evolution [J]. Viruses, 2014, 6(12): 4914-25.
[40]	MOSCHETTI R, DIMITRI P, CAIZZI R, et al. Genomic instability of I elements of Drosophila melanogaster in absence of dysgenic crosses [J]. PLoS One, 2010, 5(10).
[41]	JAILLET J, GENTY M, CAMBEFORT J, et al. Regulation of mariner transposition: the peculiar case of Mos1 [J]. PLoS One, 2012, 7(8): e43365.
[42]	CAO J, YU T, XU B, et al. Epigenetic and chromosomal features drive transposon insertion in Drosophila melanogaster [J]. Nucleic Acids Res, 2023, 51(5): 2066-86.
[43]	LOUBALOVA Z, KONSTANTINIDOU P, HAASE A D. Themes and variations on piRNA-guided transposon control [J]. Mob DNA, 2023, 14(1): 10.
[44]	ILIK I A, YANG X, ZHANG Z Z Z, et al. Transcriptional and post-transcriptional regulation of transposable elements and their roles in development and disease [J]. Nat Rev Mol Cell Biol, 2025.
[45]	JOURAVLEVA K, ZAMORE P D. A guide to the biogenesis and functions of endogenous small non-coding RNAs in animals [J]. Nat Rev Mol Cell Biol, 2025, 26(5): 347-70.
[46]	SRIVASTAV S P, FESCHOTTE C, CLARK A G. Rapid evolution of piRNA clusters in the Drosophila melanogaster ovary [J]. Genome Res, 2024, 34(5): 711-24.
[47]	PANE A, JIANG P, ZHAO D Y, et al. The Cutoff protein regulates piRNA cluster expression and piRNA production in the Drosophila germline [J]. EMBO J, 2011, 30(22): 4601-15.
[48]	SUYAMA R, KAI T. piRNA processing within non-membrane structures is governed by constituent proteins and their functional motifs [J]. FEBS J, 2025, 292(11): 2715-36.
[49]	WU P H, ZAMORE P D. Defining the functions of PIWI-interacting RNAs [J]. Nat Rev Mol Cell Biol, 2021, 22(4): 239-40.
[50]	CHARY S, HAYASHI R. The absence of core piRNA biogenesis factors does not impact efficient transposon silencing in Drosophila [J]. PLoS Biol, 2023, 21(6): e3002099.
[51]	PODVALNAYA N, BRONKHORST A W, LICHTENBERGER R, et al. piRNA processing by a trimeric Schlafen-domain nuclease [J]. Nature, 2023, 622(7982): 402-9.
[52]	DE BRITO T F, ARRUDA CARDOSO M, ATINBAYEVA N, et al. Embryonic piRNAs target horizontally transferred vertebrate transposons in assassin bugs [J]. Front Cell Dev Biol, 2024, 12: 1481881.
[53]	VAN LOPIK J, ALIZADA A, TRAPOTSI M A, et al. Unistrand piRNA clusters are an evolutionarily conserved mechanism to suppress endogenous retroviruses across the Drosophila genus [J]. Nat Commun, 2023, 14(1): 7337.
[54]	JONES B C, WOOD J G, CHANG C, et al. A somatic piRNA pathway in the Drosophila fat body ensures metabolic homeostasis and normal lifespan [J]. Nat Commun, 2016, 7: 13856.
[55]	LEWIS S H, QUARLES K A, YANG Y, et al. Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements [J]. Nat Ecol Evol, 2018, 2(1): 174-81.
[56]	YU T, BLYTON M B J, ABAJORGA M, et al. Evolution of KoRV-A transcriptional silencing in wild koalas [J]. Cell, 2025, 188(8): 2081-93 e16.
[57]	YU T, KOPPETSCH B S, PAGLIARANI S, et al. The piRNA Response to Retroviral Invasion of the Koala Genome [J]. Cell, 2019, 179(3): 632-43 e12.
[58]	GEBERT D, NEUBERT L K, LLOYD C, et al. Large Drosophila germline piRNA clusters are evolutionarily labile and dispensable for transposon regulation [J]. Mol Cell, 2021, 81(19): 3965-78 e5.
[59]	WOOD J G, JONES B C, JIANG N, et al. Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila [J]. Proc Natl Acad Sci U S A, 2016, 113(40): 11277-82.
[60]	ZHANG G, YU T, PARHAD S S, et al. piRNA-independent transposon silencing by the Drosophila THO complex [J]. Dev Cell, 2021, 56(18): 2623-35 e5.
[61]	SONG J, LIU J, SCHNAKENBERG S L, et al. Variation in piRNA and transposable element content in strains of Drosophila melanogaster [J]. Genome Biol Evol, 2014, 6(10): 2786-98.
[62]	ZATTERA M L, BRUSCHI D P. Transposable Elements as a Source of Novel Repetitive DNA in the Eukaryote Genome [J]. Cells, 2022, 11(21).
[63]	CASACUBERTA E. Drosophila: Retrotransposons Making up Telomeres [J]. Viruses, 2017, 9(7).
[64]	LEVIS R W, GANESAN R, HOUTCHENS K, et al. Transposons in place of telomeric repeats at a Drosophila telomere [J]. Cell, 1993, 75(6): 1083-93.
[65]	PIETZENUK B, MARKUS C, GAUBERT H, et al. Recurrent evolution of heat-responsiveness in Brassicaceae COPIA elements [J]. Genome Biol, 2016, 17(1): 209.
[66]	WIDEN S A, BES I C, KORESHOVA A, et al. Virus-like transposons cross the species barrier and drive the evolution of genetic incompatibilities [J]. Science, 2023, 380(6652): eade0705.
[67]	SCHWARZ F, WIERZBICKI F, SENTI K A, et al. Tirant Stealthily Invaded Natural Drosophila melanogaster Populations during the Last Century [J]. Mol Biol Evol, 2021, 38(4): 1482-97.
[68]	PASTUZYN E D, DAY C E, KEARNS R B, et al. The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer [J]. Cell, 2018, 172(1-2): 275-88 e18.
[69]	ASHLEY J, CORDY B, LUCIA D, et al. Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons [J]. Cell, 2018, 172(1-2): 262-74 e11.
[70]	KLUMPE S, SENTI K A, BECK F, et al. In-cell structure and snapshots of copia retrotransposons in intact tissue by cryo-ET [J]. Cell, 2025, 188(8): 2094-110 e18.
[71]	WANG L, TRACY L, SU W, et al. Retrotransposon activation during Drosophila metamorphosis conditions adult antiviral responses [J]. Nat Genet, 2022, 54(12): 1933-45.
[72]	CHANG Y H, KEEGAN R M, PRAZAK L, et al. Cellular labeling of endogenous retrovirus replication (CLEVR) reveals de novo insertions of the gypsy retrotransposable element in cell culture and in both neurons and glial cells of aging fruit flies [J]. PLoS Biol, 2019, 17(5): e3000278.
[73]	HOU Y, LI Y, XIANG J F, et al. TDP-43 chronic deficiency leads to dysregulation of transposable elements and gene expression by affecting R-loop and 5hmC crosstalk [J]. Cell Rep, 2024, 43(1): 113662.
[74]	KRUG L, CHATTERJEE N, BORGES-MONROY R, et al. Retrotransposon activation contributes to neurodegeneration in a Drosophila TDP-43 model of ALS [J]. PLoS Genet, 2017, 13(3): e1006635.
[75]	SONG S U, GERASIMOVA T, KURKULOS M, et al. An env-like protein encoded by a Drosophila retroelement: evidence that gypsy is an infectious retrovirus [J]. Genes Dev, 1994, 8(17): 2046-57.
[76]	YOTH M, MAUPETIT-MEHOUAS S, AKKOUCHE A, et al. Reactivation of a somatic errantivirus and germline invasion in Drosophila ovaries [J]. Nat Commun, 2023, 14(1): 6096.
[77]	DECHAUD C, VOLFF J N, SCHARTL M, et al. Sex and the TEs: transposable elements in sexual development and function in animals [J]. Mob DNA, 2019, 10: 42.