Genome Biology最新文献_第5页

Annelid methylomes reveal ancestral developmental and aging-associated epigenetic erosion across Bilateria 蛛形纲甲基组揭示了双尾目动物祖先发育和衰老相关的表观遗传侵蚀过程

IF 12.3 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genome Biology

Pub Date : 2024-08-01 DOI: 10.1186/s13059-024-03346-z

Kero Guynes, Luke A. Sarre, Allan M. Carrillo-Baltodano, Billie E. Davies, Lan Xu, Yan Liang, Francisco M. Martín-Zamora, Paul J. Hurd, Alex de Mendoza, José M. Martín-Durán

DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as “mosaic”. Yet, the role and developmental dynamics of 5mC and how these explain interspecies differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla. Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, alongside a gradual and global, age-dependent demethylation in adult stages. Additionally, reducing 5mC levels with cytidine analogs during early development impairs normal embryogenesis and reactivates TEs in the annelid Owenia fusiformis. Our study indicates that global epigenetic erosion during development and aging is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely more important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.

以 5-甲基胞嘧啶（5mC）形式存在的 DNA 甲基化是动物体内最丰富的碱基修饰。然而，不同类群的 5mC 水平差异很大。脊椎动物基因组的甲基化水平很高，而在大多数无脊椎动物中，5mC 主要集中在持续和高度转录的基因上（基因体甲基化；GbM），在某些物种中，5mC 还集中在转座元件（TE）上，这种模式被称为 "马赛克"。然而，人们对 5mC 的作用和发育动态以及它们如何解释 DNA 甲基化模式的种间差异仍然知之甚少，尤其是在无脊椎动物的一个大支系--螺旋纲中，该支系占动物门类的近一半。在这里，我们为螺旋纲中具有不同基因组特征和系统发育位置的三个物种生成了基本分辨率的甲基组。所有可能的 5mC 模式都出现在环节动物中，从典型的无脊椎动物中间水平的镶嵌分布到高甲基化和甲基化缺失。GbM是环带动物中常见的5mC，而不同物种之间的甲基化差异可通过类群特异的转录动态或内含子TE的存在来解释。值得注意的是，GbM 与转录之间的联系在发育过程中逐渐减弱，同时在成体阶段会出现逐渐的、全面的、依赖于年龄的去甲基化。此外，在早期发育过程中，用胞苷类似物降低 5mC 水平会损害正常的胚胎发生，并重新激活环带藻 Owenia fusiformis 中的 TEs。我们的研究表明，发育和衰老过程中的整体表观遗传侵蚀是双侧动物的祖先特征。然而，转录与基因体甲基化之间的紧密联系在早期胚胎阶段可能更为重要，5mC介导的TE沉默可能是动物各系之间趋同出现的。

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引用次数: 0

Modelling the demographic history of human North African genomes points to a recent soft split divergence between populations. 对北非人类基因组的人口历史进行建模表明，最近出现了种群之间的软分裂分化。

IF 10.1 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genome Biology

Pub Date : 2024-07-30 DOI: 10.1186/s13059-024-03341-4

Jose M Serradell, Jose M Lorenzo-Salazar, Carlos Flores, Oscar Lao, David Comas

Background: North African human populations present a complex demographic scenario due to the presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa.

Results: We conducted a comprehensive analysis of 364 genomes to construct detailed demographic models for the North African region, encompassing its two primary ethnic groups, the Arab and Amazigh populations. This was achieved through an Approximate Bayesian Computation with Deep Learning (ABC-DL) framework and a novel algorithm called Genetic Programming for Population Genetics (GP4PG). This innovative approach enabled us to effectively model intricate demographic scenarios, utilizing a subset of 16 whole genomes at > 30X coverage. The demographic model suggested by GP4PG exhibited a closer alignment with the observed data compared to the ABC-DL model. Both point to a back-to-Africa origin of North African individuals and a close relationship with Eurasian populations. Results support different origins for Amazigh and Arab populations, with Amazigh populations originating back in Epipaleolithic times, while GP4PG supports Arabization as the main source of Middle Eastern ancestry. The GP4PG model includes population substructure in surrounding populations (sub-Saharan Africa and Middle East) with continuous decaying gene flow after population split. Contrary to ABC-DL, the best GP4PG model does not require pulses of admixture from surrounding populations into North Africa pointing to soft splits as drivers of divergence in North Africa.

Conclusions: We have built a demographic model on North Africa that points to a back-to-Africa expansion and a differential origin between Arab and Amazigh populations.

背景：北非地区的人口构成非常复杂，这是因为这里存在自生遗传成分和人口亚结构，另外还有来自中东、欧洲和撒哈拉以南非洲的大量基因流：我们对 364 个基因组进行了全面分析，为北非地区构建了详细的人口模型，其中包括两个主要民族--阿拉伯人和阿马齐格人。这是通过深度学习近似贝叶斯计算（ABC-DL）框架和一种名为人口遗传学遗传编程（GP4PG）的新型算法实现的。这种创新方法使我们能够利用覆盖率大于 30 倍的 16 个全基因组子集，有效地建立复杂的人口统计模型。与 ABC-DL 模型相比，GP4PG 提出的人口模型与观察到的数据更为吻合。两者都表明北非人起源于非洲，与欧亚人群关系密切。结果支持阿马齐格人和阿拉伯人的不同起源，阿马齐格人起源于旧石器时代，而 GP4PG 支持阿拉伯化是中东祖先的主要来源。GP4PG 模型包括周边种群（撒哈拉以南非洲和中东）的种群亚结构，种群分裂后基因流持续衰减。与 ABC-DL 模型相反，最佳的 GP4PG 模型并不需要周围人群向北非的掺杂脉冲，这表明软分裂是北非分化的驱动因素：我们建立了一个北非人口模型，该模型指出了阿拉伯人和阿马齐格人回溯到非洲的扩张和不同的起源。

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引用次数: 0

Epigenomic identification of vernalization cis-regulatory elements in winter wheat 冬小麦春化顺式调控元件的表观基因组鉴定

IF 12.3 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genome Biology

Pub Date : 2024-07-30 DOI: 10.1186/s13059-024-03342-3

Yanhong Liu, Pan Liu, Lifeng Gao, Yushan Li, Xueni Ren, Jizeng Jia, Lei Wang, Xu Zheng, Yiping Tong, Hongcui Pei, Zefu Lu

Winter wheat undergoes vernalization, a process activated by prolonged exposure to low temperatures. During this phase, flowering signals are generated and transported to the apical meristems, stimulating the transition to the inflorescence meristem while inhibiting tiller bud elongation. Although some vernalization genes have been identified, the key cis-regulatory elements and precise mechanisms governing this process in wheat remain largely unknown. In this study, we construct extensive epigenomic and transcriptomic profiling across multiple tissues—leaf, axillary bud, and shoot apex—during the vernalization of winter wheat. Epigenetic modifications play a crucial role in eliciting tissue-specific responses and sub-genome-divergent expressions during vernalization. Notably, we observe that H3K27me3 primarily regulates vernalization-induced genes and has limited influence on vernalization-repressed genes. The integration of these datasets enables the identification of 10,600 putative vernalization-related regulatory elements including distal accessible chromatin regions (ACRs) situated 30Kb upstream of VRN3, contributing to the construction of a comprehensive regulatory network. Furthermore, we discover that TaSPL7/15, integral components of the aging-related flowering pathway, interact with the VRN1 promoter and VRN3 distal regulatory elements. These interactions finely regulate their expressions, consequently impacting the vernalization process and flowering. Our study offers critical insights into wheat vernalization’s epigenomic dynamics and identifies the putative regulatory elements crucial for developing wheat germplasm with varied vernalization characteristics. It also establishes a vernalization-related transcriptional network, and uncovers that TaSPL7/15 from the aging pathway participates in vernalization by directly binding to the VRN1 promoter and VRN3 distal regulatory elements.

冬小麦会经历春化过程，这是一个因长期暴露在低温下而激活的过程。在这一阶段，开花信号产生并传输到顶端分生组织，刺激向花序分生组织的过渡，同时抑制分蘖芽的伸长。虽然已经发现了一些春化基因，但小麦中控制这一过程的关键顺式调节元件和精确机制在很大程度上仍然未知。在这项研究中，我们构建了冬小麦春化过程中多个组织--叶片、腋芽和芽先端--的广泛表观基因组和转录组图谱。表观遗传修饰在春化过程中引起组织特异性反应和亚基因组差异表达方面发挥了关键作用。值得注意的是，我们观察到 H3K27me3 主要调控春化诱导基因，而对春化抑制基因的影响有限。整合这些数据集后，我们鉴定出了 10,600 个与春化相关的推定调控元件，包括位于 VRN3 上游 30Kb 的远端可访问染色质区域（ACR），有助于构建一个全面的调控网络。此外，我们还发现与衰老相关的开花途径的重要组成部分 TaSPL7/15 与 VRN1 启动子和 VRN3 远端调控元件相互作用。这些相互作用精细地调节了它们的表达，从而影响了春化过程和开花。我们的研究提供了对小麦春化表观基因组动态的重要见解，并确定了对开发具有不同春化特性的小麦种质至关重要的假定调控元件。研究还建立了一个与春化相关的转录网络，并发现衰老途径中的 TaSPL7/15 通过直接与 VRN1 启动子和 VRN3 远端调控元件结合参与春化。

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引用次数: 0

scCross: a deep generative model for unifying single-cell multi-omics with seamless integration, cross-modal generation, and in silico exploration scCross：通过无缝集成、跨模态生成和硅学探索统一单细胞多组学的深度生成模型

IF 12.3 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genome Biology

Pub Date : 2024-07-29 DOI: 10.1186/s13059-024-03338-z

Xiuhui Yang, Koren K. Mann, Hao Wu, Jun Ding

Single-cell multi-omics data reveal complex cellular states, providing significant insights into cellular dynamics and disease. Yet, integration of multi-omics data presents challenges. Some modalities have not reached the robustness or clarity of established transcriptomics. Coupled with data scarcity for less established modalities and integration intricacies, these challenges limit our ability to maximize single-cell omics benefits. We introduce scCross, a tool leveraging variational autoencoders, generative adversarial networks, and the mutual nearest neighbors (MNN) technique for modality alignment. By enabling single-cell cross-modal data generation, multi-omics data simulation, and in silico cellular perturbations, scCross enhances the utility of single-cell multi-omics studies.

单细胞多组学数据揭示了复杂的细胞状态，为了解细胞动态和疾病提供了重要依据。然而，多组学数据的整合也面临挑战。有些模式还没有达到成熟的转录组学的稳健性或清晰度。再加上欠成熟模式的数据稀缺和整合的复杂性，这些挑战限制了我们将单细胞组学效益最大化的能力。我们介绍了 scCross，这是一种利用变异自动编码器、生成式对抗网络和互近邻（MNN）技术进行模态配准的工具。通过支持单细胞跨模态数据生成、多组学数据模拟和硅学细胞扰动，scCross 增强了单细胞多组学研究的实用性。

引用次数: 0

Mining alternative splicing patterns in scRNA-seq data using scASfind 利用 scASfind 挖掘 scRNA-seq 数据中的替代剪接模式

IF 12.3 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genome Biology

Pub Date : 2024-07-29 DOI: 10.1186/s13059-024-03323-6

Yuyao Song, Guillermo Parada, Jimmy Tsz Hang Lee, Martin Hemberg

Single-cell RNA-seq (scRNA-seq) is widely used for transcriptome profiling, but most analyses focus on gene-level events, with less attention devoted to alternative splicing. Here, we present scASfind, a novel computational method to allow for quantitative analysis of cell type-specific splicing events using full-length scRNA-seq data. ScASfind utilizes an efficient data structure to store the percent spliced-in value for each splicing event. This makes it possible to exhaustively search for patterns among all differential splicing events, allowing us to identify marker events, mutually exclusive events, and events involving large blocks of exons that are specific to one or more cell types.

单细胞 RNA-seq（scRNA-seq）被广泛用于转录组分析，但大多数分析都集中在基因水平的事件上，而较少关注替代剪接。在这里，我们介绍一种新颖的计算方法 scASfind，它允许使用全长 scRNA-seq 数据对细胞类型特异性剪接事件进行定量分析。ScASfind 利用高效的数据结构来存储每个剪接事件的剪接入值百分比。这样，我们就可以详尽地搜索所有差异剪接事件的模式，从而识别标记事件、互斥事件以及涉及一个或多个细胞类型特异性大块外显子的事件。

引用次数: 0

Phospholipase-mediated phosphate recycling during plant leaf senescence 植物叶片衰老过程中磷脂酶介导的磷酸盐再循环

IF 12.3 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genome Biology

Pub Date : 2024-07-29 DOI: 10.1186/s13059-024-03348-x

Bao Yang, Zengdong Tan, Jiayu Yan, Ke Zhang, Zhewen Ouyang, Ruyi Fan, Yefei Lu, Yuting Zhang, Xuan Yao, Hu Zhao, Xuemin Wang, Shaoping Lu, Liang Guo

Phosphorus is a macronutrient necessary for plant growth and development and its availability and efficient use affect crop yields. Leaves are the largest tissue that uses phosphorus in plants, and membrane phospholipids are the main source of cellular phosphorus usage. Here we identify a key process for plant cellular phosphorus recycling mediated by membrane phospholipid hydrolysis during leaf senescence. Our results indicate that over 90% of lipid phosphorus, accounting for more than one-third of total cellular phosphorus, is recycled from senescent leaves before falling off the plants. Nonspecific phospholipase C4 (NPC4) and phospholipase Dζ2 (PLDζ2) are highly induced during leaf senescence, and knockouts of PLDζ2 and NPC4 decrease the loss of membrane phospholipids and delay leaf senescence. Conversely, overexpression of PLDζ2 and NPC4 accelerates the loss of phospholipids and leaf senescence, promoting phosphorus remobilization from senescent leaves to young tissues and plant growth. We also show that this phosphorus recycling process in senescent leaves mediated by membrane phospholipid hydrolysis is conserved in plants. These results indicate that PLDζ2- and NPC4-mediated membrane phospholipid hydrolysis promotes phosphorus remobilization from senescent leaves to growing tissues and that the phospholipid hydrolysis-mediated phosphorus recycling improves phosphorus use efficiency in plants.

磷是植物生长和发育所必需的一种宏量营养元素，其供应和有效利用会影响作物产量。叶片是植物使用磷的最大组织，而膜磷脂是细胞使用磷的主要来源。在这里，我们发现了叶片衰老过程中由膜磷脂水解介导的植物细胞磷循环的关键过程。我们的研究结果表明，超过 90% 的脂质磷在从植物上脱落之前被从衰老叶片中回收，占细胞总磷的三分之一以上。非特异性磷脂酶 C4（NPC4）和磷脂酶 Dζ2（PLDζ2）在叶片衰老过程中被高度诱导，PLDζ2 和 NPC4 的基因敲除会减少膜磷脂的损失并延迟叶片衰老。相反，过量表达 PLDζ2 和 NPC4 会加速磷脂的损失和叶片的衰老，促进磷从衰老叶片向幼嫩组织的再动员和植物的生长。我们还发现，衰老叶片中这种由膜磷脂水解介导的磷循环过程在植物中是保守的。这些结果表明，PLDζ2- 和 NPC4 介导的膜磷脂水解促进了磷从衰老叶片向生长组织的再动员，磷脂水解介导的磷循环提高了植物的磷利用效率。

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引用次数: 0

Author Correction: DNA methylation remodeling and the functional implication during male gametogenesis in rice 作者更正：水稻雄性配子发生过程中的 DNA 甲基化重塑及其功能影响

IF 12.3 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genome Biology

Pub Date : 2024-07-27 DOI: 10.1186/s13059-024-03344-1

Xue Li, Bo Zhu, Yue Lu, Feng Zhao, Qian Liu, Jiahao Wang, Miaomiao Ye, Siyuan Chen, Junwei Nie, Lizhong Xiong, Yu Zhao, Changyin Wu, Dao-Xiu Zhou

Author Correction: Genome Biol 25, 84 (2024)

https://doi.org/10.1186/s13059-024-03222-w

Following publication of the original article [1], the authors identified an error in Fig. 2. In Fig. 2B, a wild type pollen picture was wrongly used to represent cmt3b pollens that in fact are of wild type phenotype.

The incorrect and correct Fig. 2 is published in this correction article and the original article [1] has been updated.

Incorrect figure:

{"title":"Author Correction: DNA methylation remodeling and the functional implication during male gametogenesis in rice","authors":"Xue Li, Bo Zhu, Yue Lu, Feng Zhao, Qian Liu, Jiahao Wang, Miaomiao Ye, Siyuan Chen, Junwei Nie, Lizhong Xiong, Yu Zhao, Changyin Wu, Dao-Xiu Zhou","doi":"10.1186/s13059-024-03344-1","DOIUrl":"https://doi.org/10.1186/s13059-024-03344-1","url":null,"abstract":"Author Correction: Genome Biol 25, 84 (2024)https://doi.org/10.1186/s13059-024-03222-w Following publication of the original article [1], the authors identified an error in Fig. 2. In Fig. 2B, a wild type pollen picture was wrongly used to represent cmt3b pollens that in fact are of wild type phenotype.The incorrect and correct Fig. 2 is published in this correction article and the original article [1] has been updated.Incorrect figure: <figure><figcaption>Fig. 2</figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13059-024-03344-1/MediaObjects/13059_2024_3344_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"989\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13059-024-03344-1/MediaObjects/13059_2024_3344_Fig1_HTML.png\" width=\"685\"/></picture>Effects of cmt3a and cmt3b mutations on DNA methylation in meiocyte, microspore and sperm. a Transcript levels in FPKM of rice CMT3a and CMT3b in seedling (Se), roots (Ro), meiocyte (Me), unicellular microspore (UM), sperm (S), egg (E), zygote (Z), endosperm nuclei (En, 1.5 days after fertilization) and globular embryo (GE, 3 days after fertilization) from RNA-seq data. The sperm (Kit-S) in Kitaake background was reported by Anderson et al., (2013). b The pollen grains of wild type and cmt3a and cmt3b mutants were I2-KI stained. Bars = 50 μm. c Violin plots comparing overall cytosine methylation levels of wild type and cmt3a and cmt3b mutant meiocyte (Me), unicellular microspore (UM) and sperm (S). The average methylation levels (white dots) and median values (black bars) in transposable elements (TE) are shown. Values of the methylomes are averages from the two replicates. d Number of differential methylated regions (DMR) in cmt3a and cmt3b relative to wild type. Relative portions in TE (> 500 bp), TEG, gene, and Intergenic regions are indicated by different colors. e Venn diagrams showing overlapping of hypo-CHG DMRs in cmt3a and cmt3b meiocyte (left) and sperm (right) relative to wild type cells. f Box plots of DNA methylation levels of hypo-CHG DMRs in meiocyte (Me) versus microspore (UM) (upper) and sperm (S) relative to microspore (UM) (lower) in wild type, cmt3a (3a) and cmt3b (3b) cells. The significance was calculated with multiple comparison tests. Different letters on top of the bars indicate a significant difference (p < 0.05). g Genome Browser screen captures showing high CHG methylation sites in microspore relative to meiocyte and sperm decreased in cmt3b mutants (highlighted by grey)Full size image<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#ic","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":null,"pages":null},"PeriodicalIF":12.3,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141768536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SonicParanoid2: fast, accurate, and comprehensive orthology inference with machine learning and language models SonicParanoid2：利用机器学习和语言模型进行快速、准确和全面的选系推断

IF 12.3 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genome Biology

Pub Date : 2024-07-25 DOI: 10.1186/s13059-024-03298-4

Salvatore Cosentino, Sira Sriswasdi, Wataru Iwasaki

Accurate inference of orthologous genes constitutes a prerequisite for comparative and evolutionary genomics. SonicParanoid is one of the fastest tools for orthology inference; however, its scalability and accuracy have been hampered by time-consuming all-versus-all alignments and the existence of proteins with complex domain architectures. Here, we present a substantial update of SonicParanoid, where a gradient boosting predictor halves the execution time and a language model doubles the recall. Application to empirical large-scale and standardized benchmark datasets shows that SonicParanoid2 is much faster than comparable methods and also the most accurate. SonicParanoid2 is available at https://gitlab.com/salvo981/sonicparanoid2 and https://zenodo.org/doi/10.5281/zenodo.11371108 .

准确推断同源基因是比较和进化基因组学的先决条件。SonicParanoid 是最快的正交推断工具之一；然而，由于全对全排列耗时，而且存在具有复杂结构域的蛋白质，它的可扩展性和准确性受到了阻碍。在这里，我们介绍了 SonicParanoid 的重大更新，其中梯度提升预测器将执行时间缩短了一半，语言模型将召回率提高了一倍。在经验性大规模标准化基准数据集上的应用表明，SonicParanoid2 比同类方法快得多，也最准确。SonicParanoid2 可在 https://gitlab.com/salvo981/sonicparanoid2 和 https://zenodo.org/doi/10.5281/zenodo.11371108 上查阅。

引用次数: 0

The vast majority of somatic mutations in plants are layer-specific 植物的绝大多数体细胞突变都具有层特异性

IF 12.3 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genome Biology

Pub Date : 2024-07-24 DOI: 10.1186/s13059-024-03337-0

Manish Goel, José A. Campoy, Kristin Krause, Lisa C. Baus, Anshupa Sahu, Hequan Sun, Birgit Walkemeier, Magdalena Marek, Randy Beaudry, David Ruiz, Bruno Huettel, Korbinian Schneeberger

Plant meristems are structured organs consisting of distinct layers of stem cells, which differentiate into new plant tissue. Mutations in meristematic layers can propagate into large sectors of the plant. However, the characteristics of meristematic mutations remain unclear, limiting our understanding of the genetic basis of somaclonal phenotypic variation. Here, we analyse the frequency and distribution of somatic mutations in an apricot tree. We separately sequence the epidermis (developing from meristem layer 1) and the flesh (developing from meristem layer 2) of several fruits sampled across the entire tree. We find that most somatic mutations (> 90%) are specific to individual layers. Interestingly, layer 1 shows a higher mutation load than layer 2, implying different mutational dynamics between the layers. The distribution of somatic mutations follows the branching of the tree. This suggests that somatic mutations are propagated to developing branches through axillary meristems. In turn, this leads us to the unexpected observation that the genomes of layer 1 of distant branches are more similar to each other than to the genomes of layer 2 of the same branches. Finally, using single-cell RNA sequencing, we demonstrate that layer-specific mutations were only transcribed in the cells of the respective layers and can form the genetic basis of somaclonal phenotypic variation. Here, we analyse the frequency and distribution of somatic mutations with meristematic origin. Our observations on the layer specificity of somatic mutations outline how they are distributed, how they propagate, and how they can impact clonally propagated crops.

植物分生组织是由不同干细胞层组成的结构器官，它们分化成新的植物组织。分生组织层的突变可传播到植物的大部分区域。然而，分生组织突变的特征仍不清楚，限制了我们对体细胞表型变异遗传基础的了解。在这里，我们分析了杏树体细胞突变的频率和分布。我们分别对整棵树上几个果实的表皮（由分生组织第 1 层发育而成）和果肉（由分生组织第 2 层发育而成）进行了测序。我们发现，大多数体细胞突变（> 90%）都是单个果层特有的。有趣的是，第 1 层比第 2 层显示出更高的突变负荷，这意味着各层之间存在不同的突变动态。体细胞突变的分布与树的分支一致。这表明体细胞突变是通过腋生分生组织传播到发育中的枝条上的。反过来，这又使我们发现了一个意想不到的现象，即相距较远的树枝的第1层基因组比相同树枝的第2层基因组更加相似。最后，通过单细胞 RNA 测序，我们证明了层特异性突变只在相应层的细胞中转录，并能形成体细胞表型变异的遗传基础。在这里，我们分析了起源于分生组织的体细胞突变的频率和分布。我们对体细胞突变的层特异性的观察概括了体细胞突变的分布、传播方式以及对克隆繁殖作物的影响。

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引用次数: 0

N6-methyladenosine writer METTL16-mediated alternative splicing and translation control are essential for murine spermatogenesis N6-甲基腺苷作家 METTL16 介导的替代剪接和翻译控制对小鼠精子发生至关重要

IF 12.3 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genome Biology

Pub Date : 2024-07-19 DOI: 10.1186/s13059-024-03332-5

Qian Ma, Yiqian Gui, Xixiang Ma, Bingqian Zhang, Wenjing Xiong, Shiyu Yang, Congcong Cao, Shaomei Mo, Ge Shu, Jing Ye, Kuan Liu, Xiaoli Wang, Yaoting Gui, Fengli Wang, Shuiqiao Yuan

The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional knockout of Mettl16 in male mice impairs spermatogonial differentiation and meiosis initiation. Mechanistically, METTL16 interacts with splicing factors to regulate the alternative splicing of meiosis-related genes such as Stag3. Ribosome profiling reveals that the translation efficiency of many meiotic genes is dysregulated in METTL16-deficient testes. m6A-sequencing shows that ablation of METTL16 causes upregulation of the m6A-enriched transcripts and downregulation of the m6A-depleted transcripts, similar to Meioc and/or Ythdc2 mutants. Further in vivo and in vitro experiments demonstrate that the methyltransferase activity site (PP185-186AA) of METTL16 is necessary for spermatogenesis. Our findings support a molecular model wherein the m6A writer METTL16-mediated alternative splicing and translation efficiency regulation are required to control the mitosis-to-meiosis germ cell fate decision in mice, with implications for understanding meiosis-related male fertility disorders.

精子发生过程中从有丝分裂到减数分裂的转换需要基因表达的动态变化。然而，在这一转变过程中，减数分裂转录和转录后机制的调控仍然难以捉摸。我们报告说，精子发生过程中的有丝分裂到减数分裂转换需要N6-甲基腺苷（m6A）写入器--甲基转移酶样蛋白16（METTL16）。在雄性小鼠中基因条件性敲除 Mettl16 会损害精原细胞分化和减数分裂的启动。从机制上讲，METTL16与剪接因子相互作用，调节减数分裂相关基因（如Stag3）的替代剪接。核糖体分析表明，在 METTL16 基因缺陷的睾丸中，许多减数分裂基因的翻译效率失调。m6A 序列测定显示，消减 METTL16 会导致 m6A 富集转录本上调，而 m6A 缺失转录本下调，这与 Meioc 和/或 Ythdc2 突变体类似。进一步的体内和体外实验证明，METTL16的甲基转移酶活性位点（PP185-186AA）是精子发生所必需的。我们的研究结果支持一种分子模型，即小鼠有丝分裂到减数分裂的生殖细胞命运决定需要由 m6A 作家 METTL16 介导的替代剪接和翻译效率调控，这对理解与减数分裂相关的男性生育障碍具有重要意义。

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引用次数: 0

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