Journal of Genetics and Genomics

Finding unknown species in the genomes of extant species

Yan Li, Dong-Dong Wu

2021, 48(10): 867-871. doi: 10.1016/j.jgg.2021.05.013

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Abstract:
Although many species have gone extinct, their genetic components might exist in extant species because of ancient hybridization. Via advances in genome sequencing and development of modern population genetics, one can find the legacy of unknown or extinct species in the context of available genomes from extant species. Such discovery can be used as a strategy to search for hidden species or fossils in conservation biology and archeology, gain novel insight into complex evolutionary history, and provide the new sources of genetic variation for breeding and trait improvement in agriculture.

Phase separation in RNA biology

Yi Lin, Xiaofeng Fang

2021, 48(10): 872-880. doi: 10.1016/j.jgg.2021.07.012

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Abstract:
The formation of biomolecular condensates via liquid-liquid phase separation (LLPS) is an advantageous strategy for cells to organize subcellular compartments for diverse functions. The involvement of LLPS is more widespread and overrepresented in RNA-related biological processes. This is in part because that RNAs are intrinsically multivalent macromolecules, and the presence of RNAs affects the formation, dissolution, and biophysical properties of biomolecular condensates formed by LLPS. Emerging studies have illustrated how LLPS participates in RNA transcription, splicing, processing, quality control, translation, and function. The interconnected regulation between LLPS and RNAs ensures tight control of RNA-related cellular functions.

Single-cell transcriptome atlas of the leaf and root of rice seedlings

Yu Wang, Qing Huan, Ke Li, Wenfeng Qian

2021, 48(10): 881-898. doi: 10.1016/j.jgg.2021.06.001

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Abstract:
As a multicellular organism, rice flourishes relying on gene expression diversity among cells of various functions. However, cellular-resolution transcriptome features are yet to be fully recognized, let alone cell-specific transcriptional responses to environmental stimuli. In this study, we apply single-cell RNA sequencing to both shoot and root of rice seedlings growing in Kimura B nutrient solution or exposed to various abiotic stresses and characterize transcriptomes for a total of 237,431 individual cells. We identify 15 and 9 cell types in the leaf and root, respectively, and observe that common transcriptome features are often shared between leaves and roots in the same tissue layer, except for endodermis or epidermis. Abiotic stress stimuli alter gene expression largely in a cell type-specific manner, but for a given cell type, different stresses often trigger transcriptional regulation of roughly the same set of genes. Besides, we detect proportional changes in cell populations in response to abiotic stress and investigate the underlying molecular mechanisms through single-cell reconstruction of the developmental trajectory. Collectively, our study represents a benchmark-setting data resource of single-cell transcriptome atlas for rice seedlings and an illustration of exploiting such resources to drive discoveries in plant biology.

Maternal genetic history of southern East Asians over the past 12,000 years

Yalin Liu, Tianyi Wang, Xichao Wu, Xuechun Fan, Wei Wang, Guangmao Xie, Zhen Li, Qingping Yang, Peng Cao, Ruowei Yang, Feng Liu, Qingyan Dai, Xiaotian Feng, Wanjing Ping, Bo Miao, Yun Wu, Yichen Liu, Qiaomei Fu

2021, 48(10): 899-907. doi: 10.1016/j.jgg.2021.06.002

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Abstract:
Southern East Asia, including Guangxi and Fujian provinces in China, is home to diverse ethnic groups, languages, and cultures. Previous studies suggest a high complexity regarding population dynamics and the history of southern East Asians. However, large-scale genetic studies on ancient populations in this region are hindered by limited sample preservation. Here, using highly efficient DNA capture techniques, we obtain 48 complete mitochondrial genomes of individuals from Guangxi and Fujian in China and reconstruct their maternal genetic history over the past 12,000 years. We find a strong connection between southern East Asians dating to ~12,000–6000 years ago and present-day Southeast Asians. In addition, stronger genetic affinities to northern East Asians are observed in historical southern East Asians than Neolithic southern East Asians, suggesting increased interactions between northern and southern East Asians over time. Overall, we reveal dynamic connections between ancient southern East Asians and populations located in surrounding regions, as well as a shift in maternal genetic structure within the populations over time.

Chromosome organization and gene expansion in the highly fragmented genome of the ciliate Strombidium stylifer

Chao Li, Xiao Chen, Weibo Zheng, Thomas G. Doak, Guangyi Fan, Weibo Song, Ying Yan

2021, 48(10): 908-916. doi: 10.1016/j.jgg.2021.05.014

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Abstract:
Chromosomes are well-organized carriers of genetic information in eukaryotes and are usually quite long, carrying hundreds and thousands of genes. Intriguingly, a clade of single-celled ciliates, Spirotrichea, feature nanochromosomes—also called “gene-sized chromosomes”. These chromosomes predominantly carry only one gene, flanked by short telomere sequences. However, the organization and copy number variation of the chromosomes in these highly fragmented genomes remain unexplored in many groups of Spirotrichea, including the marine Strombidium. Using deep genome sequencing, we assembled the macronuclear genome of Strombidium stylifer into more than 18,000 nanochromosomes (~2.4 Kb long on average). Our results show that S. stylifer occupies an intermediate position during the evolutionary history of Strombidium lineage and experienced significant expansions in several gene families related to guanyl ribonucleotide binding. Based on the nucleotide distribution bias analysis and conserved motifs search in non-genic regions, we found that the subtelomeric regions have a conserved adenine-thymine (AT)-rich sequence motif. We also found that the copy number of nanochromosomes lacks precise regulation. This work sheds light on the unique features of chromosome structure in eukaryotes with highly fragmented genomes and reveals that a rather specialized evolutionary strategy at the genomic level has resulted in great diversity within the ciliated lineages.

Inducible CRISPRa screen identifies putative enhancers

Zhongye Dai, Rui Li, Yuying Hou, Qian Li, Ke Zhao, Ting Li, Mulin Jun Li, Xudong Wu

2021, 48(10): 917-927. doi: 10.1016/j.jgg.2021.06.012

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Abstract:
Enhancers are critical cis-regulatory elements that regulate spatiotemporal gene expression and control cell fates. However, the identification of enhancers in native cellular contexts still remains a challenge. Here, we develop an inducible CRISPR activation (CRISPRa) system by transgenic expression of doxycycline (Dox)-inducible dCas9-VPR in mouse embryonic stem cells (iVPR ESC). With this line, a simple introduction of specific guide RNAs targeting promoters or enhancers allows us to realize the effect of CRISPRa in an inducible, reversible, and Dox concentration-dependent manner. Taking advantage of this system, we induce tiled CRISPRa across genomic regions (105 kilobases) surrounding T (Brachyury), one of the key mesodermal development regulator genes. Moreover, we identify several CRISPRa-responsive elements with chromatin features of putative enhancers, including a region the homologous sequence in which humans harbors a body height risk variant. Genetic deletion of this region in ESC does affect subsequent T gene activation and osteogenic differentiation. Therefore, our inducible CRISPRa ESC line provides a convenient platform for high-throughput screens of putative enhancers.

Correlation of DNA methylation patterns to the phenotypic features of Tibetan elite alpinists in extreme hypoxia

Zhuoma Basang, Shixuan Zhang, La Yang, Deji Quzong, Yi Li, Yanyun Ma, Meng Hao, WeiLin Pu, Xiaoyu Liu, Hongjun Xie, Meng Liang, Jiucun Wang, Qiangba Danzeng

2021, 48(10): 928-935. doi: 10.1016/j.jgg.2021.05.015

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Abstract:
High altitude is an extreme environment that imposes hypoxic pressure on physiological processes, and natives living at high altitudes are more adaptive in certain physiological processes. So far, epigenetic modifications under extreme changes in hypoxic pressures are relatively less understood. Here, we recruit 32 Tibetan elite alpinists (TEAs), who have successfully mounted Everest (8848 m) at least five times. Blood samples and physiological phenotypes of TEAs and 32 matched non-alpinist Tibetan volunteers (non-TEAs) are collected for analysis. Genome-wide DNA methylation analysis identifies 23,202 differentially methylated CpGs (P_adj <0.05, |β| >0.1) between the two groups. Some differentially methylated CpGs are in hypoxia-related genes such as PPP1R13L, MAP3K7CL, SEPTI-9, and CUL2. In addition, Gene ontology enrichment analysis reveals several inflammation-related pathways. Phenotypic analysis indicates that 12 phenotypes are significantly different between the two groups. In particular, TEAs exhibit higher blood oxygen saturation levels and lower neutrophil count, platelet count, and heart rate. For DNA methylation association analysis, we find that two CpGs (cg16687447, cg06947206) upstream of PTEN were associated with platelet count. In conclusion, extreme hypoxia exposure leads to epigenetic modifications and phenotypic alterations of TEA, providing us clues for exploring the molecular mechanism underlying changes under extreme hypoxia conditions.

Antibody upstream sequence diversity and its biological implications revealed by repertoire sequencing

Yan Zhu, Xiujia Yang, Cuiyu Ma, Haipei Tang, Qilong Wang, Junjie Guan, Wenxi Xie, Sen Chen, Yuan Chen, Minhui Wang, Chunhong Lan, Deqiang Sun, Lai Wei, Caijun Sun, Xueqing Yu, Zhenhai Zhang

2021, 48(10): 936-945. doi: 10.1016/j.jgg.2021.06.016

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Abstract:
The sequence upstream of the antibody variable region (antibody upstream sequence [AUS]) consists of a 5' untranslated region (5' UTR) and a preceding leader region. The sequence variations in AUS affect antibody engineering and PCR based antibody quantification and may also be implicated in mRNA transcription and translation. However, the diversity of AUSs remains elusive. Using 5' rapid amplification of cDNA ends and high-throughput antibody repertoire sequencing technique, we acquired full-length AUSs for human, rhesus macaque, cynomolgus macaque, mouse, and rat. We designed a bioinformatics pipeline and identified 3307 unique AUSs, corresponding to 3026 and 1457 unique sequences for 5' UTR and leader region, respectively. Comparative analysis indicated that 928 (63.69%) leader sequences are novel relative to those recorded in the international ImMunoGeneTics information system. Evolutionarily, leader sequences are more conserved than 5' UTR and seem to coevolve with their downstream V genes. Besides, single-nucleotide polymorphisms are position dependent for leader regions and may contribute to the functional reversal of the downstream V genes. Finally, the AUGs in AUSs were found to have little impact on gene expression. Taken together, our findings can facilitate primer design for capturing antibodies efficiently and provide a valuable resource for antibody engineering and molecule-level antibody studies.

Long-range gene regulation network of the MGMT enhancer modulates glioma cell sensitivity to temozolomide

Bohan Chen, Anshun He, Jinfang Bi, Shupeng Sun, Yiping Ma, Wenbin Wang, Dianhao Guo, Jun Chen, Yuyang Qian, Tengfei Shi, Guohui Nie, Zhongfang Zhao, Jiandang Shi, Hongzhen Yang, Lei Zhang, Wange Lu

2021, 48(10): 946-949. doi: 10.1016/j.jgg.2021.06.015

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Genetic manipulations of TaARE1 boost nitrogen utilization and grain yield in wheat

Meng Guo, Qing Wang, Yuan Zong, Jinqiang Nian, Hanwen Li, Junming Li, Tao Wang, Caixia Gao, Jianru Zuo

2021, 48(10): 950-953. doi: 10.1016/j.jgg.2021.07.003

Abstract (283) PDF (50)

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2021 Vol. 48, No. 10