transposable elements

转座因子
  • 文章类型: Journal Article
    转座因子(TE)是真核生物基因组的必要组分,并且受到严格的调节机制以避免其潜在的有害作用。然而,大量研究证实了TEs的复活,特别是长散布的核元素-1(LINE-1),在植入前发育过程中,老化,癌症,和其他与年龄有关的疾病。LINE-1家族也参与了几个与衰老相关的过程,包括基因组的不稳定性,异染色质的损失,DNA甲基化,和衰老相关分泌表型(SASP)。此外,LINE-1家族在癌症发展中的作用也得到了证实.该领域的研究为LINE-1活性的功能机制提供了有价值的见解,加强我们对衰老规律的理解。这篇综述全面总结了LINE-1的最新发现及其在衰老和年龄相关疾病中的作用。
    Transposable elements (TEs) are essential components of eukaryotic genomes and are subject to stringent regulatory mechanisms to avoid their potentially deleterious effects. However, numerous studies have verified the resurrection of TEs, particularly long interspersed nuclear element-1 (LINE-1), during preimplantation development, aging, cancer, and other age-related diseases. The LINE-1 family has also been implicated in several aging-related processes, including genomic instability, loss of heterochromatin, DNA methylation, and the senescence-associated secretory phenotype (SASP). Additionally, the role of the LINE-1 family in cancer development has also been substantiated. Research in this field has offered valuable insights into the functional mechanisms underlying LINE-1 activity, enhancing our understanding of aging regulation. This review provides a comprehensive summary of current findings on LINE-1 and their roles in aging and age-related diseases.
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  • 文章类型: Journal Article
    转座因子(TE)是可以在基因组中移动或复制的DNA序列,他们的研究在理解基因组进化和功能方面变得越来越重要。Tridactylidae家族,包括Xyariparia(侏儒痣板球),藏有各种未得到充分研究的转座因子(TE)。需要进一步研究以充分了解它们的多样性和进化特征。因此,我们使用染色体水平的组装基因组对X.riparia物种进行了全面的重复性分析.这项研究旨在全面分析丰度,分布,和基因组中转座因子(TE)的年龄。结果表明,基因组为1.67Gb,具有731.63Mb的重复序列,占II类(443.25Mb)的27%,I类的16%(268.45Mb),和1%的未知TEs(19.92Mb)。研究发现DNA转座子在基因组中占主导地位,约占总重复大小的60%,逆转录转座子和未知元素占基因组的37%和3%,分别。吉普赛超家族的成员是反转录转座子中最丰富的,占其中的63%。转座超家族(LTR/吉普赛,DNA/nMITE,DNA/hAT,和DNA/Helitron)共同构成了所有六个染色体总重复大小的近70%。该研究进一步揭示了染色体大小与重复序列之间的显着线性相关(皮尔逊相关:r=0.99,p值=0.00003)。DNA转座子和反转录转座子插入的平均年龄从25My(百万年)到5My。卫星组分析发现了13个卫星DNA家族,约占整个基因组的0.15%。此外,TEs的转录分析发现,DNA转座子比逆转录转座子更具转录活性。总的来说,这项研究表明,里帕里亚的基因组很复杂,以相当大一部分的重复元素为特征。这些发现不仅增强了我们对Tridactylidae家族中TE进化的理解,而且为未来对相关物种基因组复杂性的研究奠定了基础。
    Transposable elements (TEs) are DNA sequences that can move or replicate within a genome, and their study has become increasingly important in understanding genome evolution and function. The Tridactylidae family, including Xya riparia (pygmy mole cricket), harbors a variety of transposable elements (TEs) that have been insufficiently investigated. Further research is required to fully understand their diversity and evolutionary characteristics. Hence, we conducted a comprehensive repeatome analysis of X. riparia species using the chromosome-level assembled genome. The study aimed to comprehensively analyze the abundance, distribution, and age of transposable elements (TEs) in the genome. The results indicated that the genome was 1.67 Gb, with 731.63 Mb of repetitive sequences, comprising 27% of Class II (443.25 Mb), 16% of Class I (268.45 Mb), and 1% of unknown TEs (19.92 Mb). The study found that DNA transposons dominate the genome, accounting for approximately 60% of the total repeat size, with retrotransposons and unknown elements accounting for 37% and 3% of the genome, respectively. The members of the Gypsy superfamily were the most abundant amongst retrotransposons, accounting for 63% of them. The transposable superfamilies (LTR/Gypsy, DNA/nMITE, DNA/hAT, and DNA/Helitron) collectively constituted almost 70% of the total repeat size of all six chromosomes. The study further unveiled a significant linear correlation (Pearson correlation: r = 0.99, p-value = 0.00003) between the size of the chromosomes and the repetitive sequences. The average age of DNA transposon and retrotransposon insertions ranges from 25 My (million years) to 5 My. The satellitome analysis discovered 13 satellite DNA families that comprise about 0.15% of the entire genome. In addition, the transcriptional analysis of TEs found that DNA transposons were more transcriptionally active than retrotransposons. Overall, the study suggests that the genome of X. riparia is complex, characterized by a substantial portion of repetitive elements. These findings not only enhance our understanding of TE evolution within the Tridactylidae family but also provide a foundation for future investigations into the genomic intricacies of related species.
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  • 文章类型: Journal Article
    染色质动力学在转录调控中起重要作用。色域解旋酶DNA结合域3(CHD3)染色质重塑因子PICKLE(PKL)和HISTONEDEACETYLASE6(HDA6)是转录基因沉默所必需的,但是它们在基因抑制中的协调功能需要进一步研究。通过基因抑制筛选,我们发现,PKL的点突变可以部分恢复弱Polycomb抑制复合物1(PRC1)突变体(ring1a-2ring1b-3)的发育缺陷,其中RING1A表达被启动子处的T-DNA插入抑制。与ring1a-2ring1b-3相比,RING1A的表达增加,核小体占用减少,在pklring1a-2ring1b-3三重突变体中,RING1A基因座的组蛋白3赖氨酸9乙酰化(H3K9ac)水平增加。HDA6与PKL相互作用,并在环1a-2环1b-3背景中与PKL在遗传和分子上相似地抑制RING1A表达。此外,我们显示PKL和HDA6通过增加核小体密度和减少H3K9ac来抑制一组基因和转座因子(TE)的表达。全基因组分析表明,它们也可能协调维持DNA甲基化。我们的研究结果表明,PKL和HDA6共同发挥作用,以减少H3K9ac和增加核小体占有率,从而促进拟南芥(拟南芥)中的基因/TE调控。
    Chromatin dynamics play essential roles in transcriptional regulation. The chromodomain helicase DNA-binding domain 3 (CHD3) chromatin remodeler PICKLE (PKL) and HISTONE DEACETYLASE6 (HDA6) are required for transcriptional gene silencing, but their coordinated function in gene repression requires further study. Through a genetic suppressor screen, we found that a point mutation at PKL could partially restore the developmental defects of a weak Polycomb repressive complex 1 (PRC1) mutant (ring1a-2 ring1b-3), in which RING1A expression is suppressed by a T-DNA insertion at the promoter. Compared to ring1a-2 ring1b-3, the expression of RING1A is increased, nucleosome occupancy is reduced, and the histone 3 lysine 9 acetylation (H3K9ac) level is increased at the RING1A locus in the pkl ring1a-2 ring1b-3 triple mutant. HDA6 interacts with PKL and represses RING1A expression similarly to PKL genetically and molecularly in the ring1a-2 ring1b-3 background. Furthermore, we show that PKL and HDA6 suppress the expression of a set of genes and transposable elements (TEs) by increasing nucleosome density and reducing H3K9ac. Genome-wide analysis indicated they possibly coordinately maintain DNA methylation as well. Our findings suggest that PKL and HDA6 function together to reduce H3K9ac and increase nucleosome occupancy, thereby facilitating gene/TE regulation in Arabidopsis (Arabidopsis thaliana).
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  • 文章类型: Journal Article
    背景:转座因子在维持神经发育过程中的基因组结构中起着关键作用。短散布核元素(SINE),转座因子的主要亚型,已知具有CCCTC结合因子(CTCF)的结合位点,并且在协调染色质组织中至关重要。然而,在发育中的大脑中控制SINE活性的调节机制仍然难以捉摸。
    结果:在我们的研究中,我们使用ATAC-seq对小鼠神经前体细胞进行了全面的全基因组表观遗传分析,ChIP-seq,全基因组亚硫酸氢盐测序,就地Hi-C,和RNA-seq。我们的发现表明,SET结构域分叉的组蛋白赖氨酸甲基转移酶1(SETDB1)介导的H3K9me3与DNA甲基化结合,限制了神经前体细胞中选择性SINE子集的染色质可及性。机械上,Settb1的丢失会增加CTCF对这些SINE元素的访问,并有助于染色质环的重组。此外,从头环形成有助于差异基因表达,包括有丝分裂途径中富集的基因的失调。这导致在体外和体内对Setdb1进行遗传消融后胚胎脑中细胞增殖的破坏。
    结论:总之,我们的研究揭示了小鼠神经前体细胞中SINE的表观遗传调控,提示它们在维持神经发育过程中染色质组织和细胞增殖中的作用。
    BACKGROUND: Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive.
    RESULTS: In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo.
    CONCLUSIONS: In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.
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  • 文章类型: Journal Article
    转座元件(TE),占人类基因组的近50%,已经从被视为“基因组垃圾”转变为癌症进展的关键参与者。当代研究将TE监管中断与癌症发展联系起来,强调他们的治疗潜力。长读数测序的进展,计算分析,单细胞测序,蛋白质组学,和CRISPR-Cas9技术丰富了我们对TEs临床意义的理解,尤其是它们对基因组结构的影响,基因调控,和进化过程。在癌症中,TEs,包括LINE-1,Alus,和LTR,展示改变的模式,影响致瘤机制和肿瘤抑制机制。TE来源的核酸和肿瘤抗原在肿瘤免疫中起关键作用,桥接先天和适应性反应。鉴于它们在肿瘤学中的核心作用,TE靶向治疗,特别是通过逆转录酶抑制剂和表观遗传调节剂,代表了癌症治疗的新途径。将这些以TE为中心的策略与现有的化疗或免疫治疗方案相结合可以提高疗效,并为癌症治疗提供新的维度。这篇综述深入研究了最近的TE检测进展,探索它们在肿瘤发生和免疫调节中的多方面作用,讨论以TE为中心的新兴诊断和治疗方法,并预测癌症研究的未来方向。
    Transposable elements (TEs), comprising nearly 50% of the human genome, have transitioned from being perceived as \"genomic junk\" to key players in cancer progression. Contemporary research links TE regulatory disruptions with cancer development, underscoring their therapeutic potential. Advances in long-read sequencing, computational analytics, single-cell sequencing, proteomics, and CRISPR-Cas9 technologies have enriched our understanding of TEs\' clinical implications, notably their impact on genome architecture, gene regulation, and evolutionary processes. In cancer, TEs, including long interspersed element-1 (LINE-1), Alus, and long terminal repeat (LTR) elements, demonstrate altered patterns, influencing both tumorigenic and tumor-suppressive mechanisms. TE-derived nucleic acids and tumor antigens play critical roles in tumor immunity, bridging innate and adaptive responses. Given their central role in oncology, TE-targeted therapies, particularly through reverse transcriptase inhibitors and epigenetic modulators, represent a novel avenue in cancer treatment. Combining these TE-focused strategies with existing chemotherapy or immunotherapy regimens could enhance efficacy and offer a new dimension in cancer treatment. This review delves into recent TE detection advancements, explores their multifaceted roles in tumorigenesis and immune regulation, discusses emerging diagnostic and therapeutic approaches centered on TEs, and anticipates future directions in cancer research.
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  • 文章类型: Journal Article
    转座元件(TE)是在植物基因组中特别丰富的可移动DNA元件。它们长期以来被认为是垃圾DNA;然而,越来越多的证据表明,TE插入促进遗传多样性,这对于物种的适应性进化至关重要。到目前为止,研究主要研究了TEs在宿主基因附近或内部插入所产生的顺式调节作用。然而,TE来源的RNA和DNA的反式作用至今仍不清楚.TE在其序列中包含各种调节元件,其可以适应特定RNA和蛋白质的结合。最近,有人建议,这些细胞调节因子中的一些在TEs和宿主基因之间共享,对共同宿主因素的竞争是微调发展重新编程的基础。在这次审查中,我们将重点介绍和讨论植物TEs生物学功能的最新发现,特别关注它们与特定发展监管机构的竞争约束力。
    Transposable elements (TEs) are mobile DNA elements that are particularly abundant in the plant genomes. They have long been considered as junk DNA; however, a growing body of evidence suggests that TE insertions promote genetic diversity that is essential for the adaptive evolution of a species. Thus far, studies have mainly investigated the cis-acting regulatory roles of TEs generated by their insertions nearby or within the host genes. However, the trans-acting effects of TE-derived RNA and DNA remained obscure to date. TEs contain various regulatory elements within their sequences that can accommodate the binding of specific RNAs and proteins. Recently, it was suggested that some of these cellular regulators are shared between TEs and the host genes, and the competition for the common host factors underlies the fine-tuned developmental reprogramming. In this review, we will highlight and discuss the latest discoveries on the biological functions of plant TEs, with a particular focus on their competitive binding with specific developmental regulators.
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  • 文章类型: Journal Article
    背景:着丝粒在细胞分裂中起着至关重要和保守的作用,虽然它们在绿藻中的组成和进化史,陆地植物的进化祖先,仍然很大程度上未知。
    结果:我们为两种树目植物构建了端粒到端粒(T2T)组件,小球藻NS4-2和小球藻蛋白核DBH,染色体数为12和13,基因组大小为58.11Mb和53.41Mb,分别。我们使用CENH3ChIP-seq鉴定并验证了它们的着丝粒序列,类似于人类和高等植物,绿藻的着丝粒CENH3信号显示出低甲基化模式。有趣的是,这两个物种的着丝粒主要由转座因子组成,尽管它们的组成有很大差异。小球藻属中的物种显示出更多样化的着丝粒组成,主要成员包括LTR/Copia的成员,LINE/L1和LINE/RTEX系列。这与绿藻形成鲜明对比,包括莱茵衣藻,球藻次椭圆,和嗜铬动物,其中着丝粒成分具有明显的单元素成分。此外,我们观察到小球藻属内具有强烈共线性的染色体之间着丝粒的组成和结构存在显着差异,表明着丝粒序列比非着丝粒区域的序列进化更快。
    结论:这项研究不仅为绿藻的比较基因组学提供了高质量的基因组数据,而且还深入了解了早期植物着丝粒的组成和进化史。为进一步研究它们的演化奠定了重要基础。
    BACKGROUND: Centromeres play a crucial and conserved role in cell division, although their composition and evolutionary history in green algae, the evolutionary ancestors of land plants, remains largely unknown.
    RESULTS: We constructed near telomere-to-telomere (T2T) assemblies for two Trebouxiophyceae species, Chlorella sorokiniana NS4-2 and Chlorella pyrenoidosa DBH, with chromosome numbers of 12 and 13, and genome sizes of 58.11 Mb and 53.41 Mb, respectively. We identified and validated their centromere sequences using CENH3 ChIP-seq and found that, similar to humans and higher plants, the centromeric CENH3 signals of green algae display a pattern of hypomethylation. Interestingly, the centromeres of both species largely comprised transposable elements, although they differed significantly in their composition. Species within the Chlorella genus display a more diverse centromere composition, with major constituents including members of the LTR/Copia, LINE/L1, and LINE/RTEX families. This is in contrast to green algae including Chlamydomonas reinhardtii, Coccomyxa subellipsoidea, and Chromochloris zofingiensis, in which centromere composition instead has a pronounced single-element composition. Moreover, we observed significant differences in the composition and structure of centromeres among chromosomes with strong collinearity within the Chlorella genus, suggesting that centromeric sequence evolves more rapidly than sequence in non-centromeric regions.
    CONCLUSIONS: This study not only provides high-quality genome data for comparative genomics of green algae but gives insight into the composition and evolutionary history of centromeres in early plants, laying an important foundation for further research on their evolution.
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  • 文章类型: Journal Article
    虽然灰霉病在许多植物上引起灰霉病,它的近亲,葡萄孢菌,宿主特异性感染主要是蚕豆植物。探索其寄主范围狭窄的基础,产生了B.fabae菌株G12(BfabG12)的无间隙基因组序列。BfabG12基因组包含45.0Mb,具有16个染色体端粒至端粒重叠群,与相应的B.cccinereaB05.10(BcB0510)染色体显示出高同伦性和序列相似性。与BcB0510相比,它大了6%,由于许多富含AT的区域含有转座因子的残留物,但编码的基因较少(11,420vs.11,707),由于丢失了多达20个基因的染色体片段。与其BcB0510直向同源物相比,BfabG12的编码能力进一步降低了近400个基因,这些基因已通过导致截短的突变失活。鉴定了具有阶段特异性表达的用于次级代谢物生物合成的几个物种特异性基因簇。感染过程中分泌的蛋白质的比较显示出很高的相似性,包括在这两个物种中检测到的17种植物毒性蛋白。我们的数据表明,宿主特异性的B.fabae的进化发生于具有广泛宿主范围的祖先病原体,类似于B.cinerea,并伴随着基因的丢失和退化,从而降低其致病灵活性。
    While Botrytis cinerea causes gray mold on many plants, its close relative, Botrytis fabae, is host-specifically infecting predominantly faba bean plants. To explore the basis for its narrow host range, a gapless genome sequence of B. fabae strain G12 (BfabG12) was generated. The BfabG12 genome encompasses 45.0 Mb, with 16 chromosomal telomere-to-telomere contigs that show high synteny and sequence similarity to the corresponding B. cinerea B05.10 (BcB0510) chromosomes. Compared to BcB0510, it is 6% larger, due to many AT-rich regions containing remnants of transposable elements, but encodes fewer genes (11,420 vs. 11,707), due to losses of chromosomal segments with up to 20 genes. The coding capacity of BfabG12 is further reduced by nearly 400 genes that had been inactivated by mutations leading to truncations compared to their BcB0510 orthologues. Several species-specific gene clusters for secondary metabolite biosynthesis with stage-specific expression were identified. Comparison of the proteins secreted during infection revealed high similarities, including 17 phytotoxic proteins that were detected in both species. Our data indicate that evolution of the host-specific B. fabae occurred from an ancestral pathogen with wide host range similar to B. cinerea and was accompanied by losses and degeneration of genes, thereby reducing its pathogenic flexibility.
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  • 文章类型: Journal Article
    转座因子(TE)是真核生物基因组的主要组成部分,存在于几乎所有的真核生物中。TEs在物种之间和物种内部都是高度动态的,这显著影响了TE数据库的一般适用性。直翅目是昆虫纲中唯一已知的基因组显着扩大(0.93-21.48Gb)。当使用现有的TE公共数据库分析大基因组时,TE注释的效率并不令人满意。为了解决这个限制,随着更多的昆虫基因组公开可用,不断更新可用的TE资源库和对直翅目特异性文库的需求变得势在必行。这里,我们使用12种直翅目的完整基因组数据从头注释TEs,然后手动重新注释未分类的TE以构建非冗余的直翅目特异性TE库:直翅目-TElib。直翅目-TElib包含24,021个TE条目,包括13,964个未知TE的重新注释结果。直翅目-TElib中TE条目的命名采用与RepeatMasker和Dfam相同的命名,并编码为“level1/level2-level3”的三级形式。直翅目-TElib可以直接用作输入参考数据库,并且与主流重复序列分析软件如RepeatMasker和dnaPipeTE兼容。在分析直翅目物种的TEs时,与Dfam和Repbase相比,直翅目-TElib执行更好的TE注释,无论使用低覆盖测序或基因组组装数据。改进最大的TE注释结果是Angaracrisrhodopa,从基因组的7.89%增加到53.28%。最后,直翅目-TElib存储在Sqlite3中,以便于数据更新和用户访问。
    Transposable elements (TEs) are a major component of eukaryotic genomes and are present in almost all eukaryotic organisms. TEs are highly dynamic between and within species, which significantly affects the general applicability of the TE databases. Orthoptera is the only known group in the class Insecta with a significantly enlarged genome (0.93-21.48 Gb). When analyzing the large genome using the existing TE public database, the efficiency of TE annotation is not satisfactory. To address this limitation, it becomes imperative to continually update the available TE resource library and the need for an Orthoptera-specific library as more insect genomes are publicly available. Here, we used the complete genome data of 12 Orthoptera species to de novo annotate TEs, then manually re-annotate the unclassified TEs to construct a non-redundant Orthoptera-specific TE library: Orthoptera-TElib. Orthoptera-TElib contains 24,021 TE entries including the re-annotated results of 13,964 unknown TEs. The naming of TE entries in Orthoptera-TElib adopts the same naming as RepeatMasker and Dfam and is encoded as the three-level form of \"level1/level2-level3\". Orthoptera-TElib can be directly used as an input reference database and is compatible with mainstream repetitive sequence analysis software such as RepeatMasker and dnaPipeTE. When analyzing TEs of Orthoptera species, Orthoptera-TElib performs better TE annotation as compared to Dfam and Repbase regardless of using low-coverage sequencing or genome assembly data. The most improved TE annotation result is Angaracris rhodopa, which has increased from 7.89% of the genome to 53.28%. Finally, Orthoptera-TElib is stored in Sqlite3 for the convenience of data updates and user access.
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  • 文章类型: Journal Article
    转座因子(TE)的移动性能够产生大量的结构变体(SV),作为家畜遗传分析和分子育种的分子标记具有相当大的潜力。我们的结果表明,猪基因组主要包含由短散布核元素(SINE)产生的TE-SV(51,873/76.49%),其次是长散布核元素(LINEs)(11,131/16.41%),和超过84%的常见TE-SV(次要等位基因频率,MAF>0.10)被验证为多态。随后,我们利用确定的TE-SV来深入了解种群结构,导致三个猪群之间的明显差异,并有助于识别中国当地猪种之间的关系。此外,我们调查了不同猪群基因编码区的TEs频率,并注释了相应的TE类型,相关基因和功能通路。通过利用北京黑猪对大型白猪和中国本地猪进行全基因组比较,我们确定了TE介导的SVs与数量性状位点(QTLs)相关,并观察到它们主要涉及car体性状和肉质性状。最后,我们提出了猪基因组中TE转导的第一个证据。
    Transposable elements (TEs) mobility is capable of generating a large number of structural variants (SVs), which can have considerable potential as molecular markers for genetic analysis and molecular breeding in livestock. Our results showed that the pig genome contains mainly TE-SVs generated by short interspersed nuclear elements (51,873/76.49%), followed by long interspersed nuclear elements (11,131/16.41%), and more than 84% of the common TE-SVs (Minor allele frequency, MAF > 0.10) were validated to be polymorphic. Subsequently, we utilized the identified TE-SVs to gain insights into the population structure, resulting in clear differentiation among the three pig groups and facilitating the identification of relationships within Chinese local pig breeds. In addition, we investigated the frequencies of TEs in the gene coding regions of different pig groups and annotated the respective TE types, related genes, and functional pathways. Through genome-wide comparisons of Large White pigs and Chinese local pigs utilizing the Beijing Black pigs, we identified TE-mediated SVs associated with quantitative trait loci and observed that they were mainly involved in carcass traits and meat quality traits. Lastly, we present the first documented evidence of TE transduction in the pig genome.
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