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Genomic Mutations within the Host Microbiome: Adaptive Evolution or Purifying Selection Review
Jiachao Zhang,Rob Knight,
Engineering 2023, Volume 20, Issue 1, Pages 96-102 doi: 10.1016/j.eng.2021.11.018
Next-generation sequencing technology has transformed our ability to assess the taxonomic composition functions of host-associated microbiota and microbiomes. More human microbiome research projects—particularly those that explore genomic mutations within the microbiome—will be launched in the next decade. This review focuses on the coevolution of microbes within a microbiome, which shapes strain-level diversity both within and between host species. We also explore the correlation between microbial genomic mutations and common metabolic diseases, and the adaptive evolution of pathogens and probiotics during invasion and colonization. Finally, we discuss advances in methods and algorithms for annotating and analyzing microbial genomic mutations.
Keywords： Gut microbiota Genomic mutations Adaptive evolution Purifying selection Single-nucleotide variants
Twelve Years of Genome-Wide Association Studies of Human Protein N-Glycosylation Review
Anna Timoshchuk, Sodbo Sharapov, Yurii S. Aulchenko
Engineering 2023, Volume 26, Issue 7, Pages 17-31 doi: 10.1016/j.eng.2023.03.013
Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains, or glycans. Glycosylation influences the physical and chemical properties of proteins, as well as their biological functions. Unsurprisingly, alterations in protein glycosylation have been implicated in a growing number of human diseases, and glycans are increasingly being considered as potential therapeutic targets, an essential part of therapeutics, and biomarkers. Although glycosylation pathways are biochemically well-studied, little is known about the networks of genes that guide the cell- and tissue-specific regulation of these biochemical reactions in humans in vivo. The lack of a detailed understanding of the mechanisms regulating glycome variation and linking the glycome to human health and disease is slowing progress in clinical applications of human glycobiology. Two of the tools that can provide much sought-after knowledge of human in vivo glycobiology are human genetics and genomics, which offer a powerful data-driven agnostic approach for dissecting the biology of complex traits. This review summarizes the current state of human populational glycogenomics. In Section 1, we provide a brief overview of the N-glycan's structural organization, and in Section 2, we give a description of the major blood plasma glycoproteins. Next, in Section 3, we summarize, systemize, and generalize the results from current N-glycosylation genome-wide association studies (GWASs) that provide novel knowledge of the genetic regulation of the populational variation of glycosylation. Until now, such studies have been limited to an analysis of the human blood plasma N-glycome and the N-glycosylation of immunoglobulin G and transferrin. While these three glycomes make up a rather limited set compared with the enormous multitude of glycomes of different tissues and glycoproteins, the study of these three does allow for powerful analysis and generalization. Finally, in Section 4, we turn to genes in the established loci, paying particular attention to genes with strong support in Section 5. At the end of the review, in Sections 6 and 7, we describe special cases of interest in light of new discoveries, focusing on possible mechanisms of action and biological targets of genetic variation that have been implicated in human protein N-glycosylation.
Keywords： Glycome Glycans N-glycosylation Genomics Genetics GWAS
Qian Zhou, Ya-dong Chen, Sheng Lu, Yang Liu, Wen-teng Xu, Yang-zhen Li, Lei Wang, Na Wang, Ying-ming Yang, Song-lin Chen
Engineering 2021, Volume 7, Issue 3, Pages 406-411 doi: 10.1016/j.eng.2020.06.017
Single nucleotide polymorphism (SNP) arrays are a powerful genotyping tool used in genetic research and genomic breeding programs. Japanese flounder (Paralichthys olivaceus) is an economically-important aquaculture flatfish in many countries. However, the lack of high-efficient genotyping tools has impeded the genomic breeding programs for Japanese flounder. We developed a 50K Japanese flounder SNP array, "Yuxin No. 1," and report its utility in genomic selection (GS) for disease resistance to bacterial pathogens. We screened more than 42.2 million SNPs from the whole-genome resequencing data of 1099 individuals and selected 48 697 SNPs that were evenly distributed across the genome to anchor the array with Affymetrix Axiom genotyping technology. Evaluation of the array performance with 168 fish showed that 74.7% of the loci were successfully genotyped with high call rates (> 98%) and that the polymorphic SNPs had good cluster separations. More than 85% of the SNPs were concordant with SNPs obtained from the whole-genome resequencing data. To validate "Yuxin No. 1" for GS, the arrayed genotyping data of 27 individuals from a candidate population and 931 individuals from a reference population were used to calculate the genomic estimated breeding values (GEBVs) for disease resistance to Edwardsiella tarda. There was a 21.2% relative increase in the accuracy of GEBV using the weighted genomic best linear unbiased prediction (wGBLUP), compared to traditional pedigree-based best linear unbiased prediction (ABLUP), suggesting good performance of the "Yuxin No. 1" SNP array for GS. In summary, we developed the "Yuxin No. 1" 50K SNP array, which provides a useful platform for high-quality genotyping that may be beneficial to the genomic selective breeding of Japanese flounder.
Albert Stuart Reece
Engineering 2023, Volume 26, Issue 7, Pages 16-16 doi: 10.1016/j.eng.2022.07.011
The central dogma of biology holds that the transcription of DNA into RNA and the translation of RNA into proteins forms the primary axis of biological activity [1]. Following major advances in the description of the complex glycan and lipid chains that are added onto these basic building blocks, the glycome and lipidome have recently been added to this doctrine as an exciting new extension named the ‘‘paracentral dogma” [2]. However, it has been pointed out that biological systems can include many layers, which are described in modern omics technology platforms relating to both cell-intrinsic and cell-extrinsic layers of control, including metabolomic, microbiomic, immunological, epigenomic, epitranscriptomic, proteomic and phosphoproteomic layers [3].
It is well known that stem and progenitor cells have a metabolism that is based on glycolysis and glutaminolysis [4]. Although this provides less energy to the cell than oxidative phosphorylation, it suffices for these cells’ needs, since such cells are generally relatively quiescent and normally suppress energy-intensive processes such as genome duplication and transcription. Moreover, it has been shown that the high intracellular lactate levels involved in such states not only inhibits the key gatekeeper enzymes of oxidative phosphorylation (i.e., pyruvate dehydrogenase and carnitine palmitoyl acyltransferase) but also actually covalently modifies them by lactylation in order to maintain this inhibited metabolic–epigenomic state [5]. In addition, intermediate metabolism and nutrients are the source of the very extensive library of post-translational modifications to DNA, RNA, and proteins, as well as supplying cellular energy for many of the required reactions. Hence, the metabolic state locks in and reinforces the epigenomic state, and the metabolome and epigenome thereby play mutually reinforcing roles. This self-reinforcing coordination explains why it is so difficult to generate induced pluripotent cells and is a contributory explanation for why the described protocols typically have such low cellular yields.
These concepts become even more important when it is considered that cancer cells are de-differentiated, similarly rely on glycolysis and glutaminolysis, and are similarly metabolically–epigenomically–genomically synchronized. The disruption of this metabolic system is a key focus of mechanistic cancer research.
These important considerations imply that the descriptive and predictive power of the newly described ‘‘paracentral dogma” of biology may be usefully and meaningfully extended by including the metabolome, along with the genome, transcriptome, proteome, glycome, and lipidome, to describe cell-intrinsic regulation—not only in terms of another omics analytical layer but also as a fully predictive and interactive partner in the symphonic-like multilayer coordination that evidently comprises cellular regulatory layering.
The Materials Genome Initiative and Advanced Materials
Liquan Chen
Engineering 2015, Volume 1, Issue 2, Pages 169-169 doi: 10.15302/J-ENG-2015056
Genomic Sequencing Costs Set to Head Down Again
Robert Pollie
Engineering 2023, Volume 23, Issue 4, Pages 3-6 doi: 10.1016/j.eng.2023.02.002
Core Metabolic Features and Hot Origin of Bathyarchaeota Article
Xiaoyuan Feng, Yinzhao Wang, Rahul Zubin, Fengping Wang
Engineering 2019, Volume 5, Issue 3, Pages 498-504 doi: 10.1016/j.eng.2019.01.011
The archaeal phylum Bathyarchaeota comprises highly diversified subgroups and is considered to be one of the most abundant microorganisms on earth. The metabolic features and evolution of this phylum still remain largely unknown. In this article, a comparative metabolic analysis of 15 newly reconstructed and 36 published metagenomic assembled genomes (MAGs) spanning 10 subgroups was performed, revealing the core metabolic features of Bathyarchaeota—namely, protein, lipid, and benzoate degradation; glycolysis; and the Wood–Ljungdahl (WL) pathway, indicating an acetyl-CoA-centralized metabolism within this phylum. Furthermore, a partial tricarboxylic acid (TCA) cycle, acetogenesis, and sulfur-related metabolic pathways were found in specific subgroups, suggesting versatile metabolic capabilities and ecological functions of different subgroups. Intriguingly, most of the MAGs from the Bathy-21 and -22 subgroups, which are placed at the phylogenetic root of all bathyarchaeotal lineages and likely represent the ancient Bathyarchaeota types, were found in hydrothermal environments and encoded reverse gyrase, suggesting a hyperthermophilic feature. This work reveals the core metabolic features of Bathyarchaeota, and indicates a hot origin of this archaeal phylum.
Keywords： Bathyarchaeota Metagenomics Comparative genomics Hyperthermophilic adaptation
Polar Animal Genetic Resources: Current Situation and Development Strategies
Chen Songlin, Xu Wenteng, Chen Zhangfan
Strategic Study of CAE 2019, Volume 21, Issue 6, Pages 39-47 doi: 10.15302/J-SSCAE-2019.06.007
This article has reviewed the current status of polar animal genetic resources and proposed the development strategies based on existing problems. Genome sequencing of polar animals started late, and the whole genome sequencing has been conducted so far on only 13 polar animals. Transcriptome sequencing has been carried out for 31 polar animals in recent years, and the transcriptome research has focused on adaption to polar environments, molecular mechanisms in response to pollutant stresses, transcriptome changes during various development stages or within different tissues, and exploitation of functional genes. The late initiation in the study of polar animal genetic resources limited its current depth and width in research. However, this study is strategically important. We suggest that China set up a key research and development program “exploration and application of biological gene resources in polar animals” to support the work in this field, and focus on genetic dissection of special traits, functional analysis of specific genes, and development of genetically engineered products.
Keywords： polar animal genome transcriptome genetic resources
Advancing Genomic Science Opens Windows to the Past
Sarah C.P. Williams
Engineering 2023, Volume 26, Issue 7, Pages 9-11 doi: 10.1016/j.eng.2023.05.003
Complete Genome Sequence of Shigella flexneri 2a 301 Strain and Analysis of “Shigella-islands”
Liu Hong,Yang Fan,Zhang Xiaobing,Zhang Jiyu,Yang Guowei,Dong Jie,Xue Ying,Hou Yunde,Yuan Zhenghong,Wen Yumei,Xu Jianguo,Cheng Hongsong,Ma Dalong,Wang Yu,Yang Jian,Shen Yan,Qiang Boqin,Wu Hongtao,Lü Weichuan,Jin Qi
Strategic Study of CAE 2002, Volume 4, Issue 10, Pages 40-47
Shigella flexneri serotype 2a are the most prevalent species and serotype that cause .bacillary dysentery or shigellosis in man. This paper presents the complete genome sequence of a Shigella flexneri 2a strain which isolated from the Beijing outbreak, and the primary analysis of “ Shigella-genomic islands (SIs)，” that means Shigella flexneri 2a 301 strain-specific genome fragments. The whole genome is composed of a 4,607,203 bp chromosome and a 221,618 bp virulence plasmid, designated pCP301. The chromosome shares a conserved ‘backbone’ sequence about 4.03 Mb with those of a benign laboratory strain E. coli K12 (MG1655) which is essentially collinear. Sf301 has 572 Kb specific-sequence which form into 320 Sis with sizes greater than 50 bp and encoding in total 519 Shigella-specific Open Reading Frames (ORFs). Among these Sis, there are 131 islands with sizes greater than 1 Kb with repeated sequences of transposable elements, transposons or tRNAs flanking on one or both sides. The average G + C content of the Sis is 48.25% , significantly lower than that of the conserved backbone. Frequency of codons such as ACA, AAT, GCG, CTG, etc. , on Sis are quite distinct from that on backbone sequences. All above observations together suggest that many of the Sis are foreign origin. Among them, the authors identified 7 putative Sis with typical structure of pathogenicity islands (PAI) and 2 Sis harbor some ORFs related to biosynthesis of lipopolysaccharide (LPS) have implications in virulence, in addition to the previously identified PAIs, SHE and SHI-2. The other Sis are mostly a mosaic of genes of known function and ORFs encoding polypeptides sharing none or low homology with known proteins from one or more bacterial species. All of these could be subjected to investigations towards novel preventive and treatment strategies against shigellosis.
Keywords： Shigella flexneri 2a 301 strain genome sequence genomic island pathogenicity island
Xia Jiahui
Strategic Study of CAE 2000, Volume 2, Issue 11, Pages 1-11
In this paper, the study on family collection, gene mapping, gene identification and gene function of human genetic diseases carried out in the National Laboratory of Medical Genetics of China, were described in detail. Using G-banding technique a marker chromosome t (1; 3) (q44; p11) associated with nasopharyngeal cancer was found in 1975 at first, and human TDF gene was mapped to chromosome Yp11. 32 in 1981. Since 1991, 590 families with 345 kind of genetic diseases were collected. In 1998, GJB3, a human genetic neurological deafness gene, was identified using a novel strategy of “Gene Family-Candidate Disease Gene Cloning”，and the paper was published in Nature Genetics (20： 370). In 1999, by linkage analysis and Genome Wide Scanning, a locus responsible for disseminated superficial actinic porokeratosis (DSAP) was identified at Chromosome 12q23. 2 - 24. 1; and at the same year a novel protein trafficking gene was also cloned from gene function study.
Keywords： genetic disease gene mapping and cloning gene familiy-candidate disease gene cloning genome wide scan gene function study
Information Science Should Take a Lead in Future Biomedical Research Perspective
Kenta Nakai
Engineering 2019, Volume 5, Issue 6, Pages 1155-1158 doi: 10.1016/j.eng.2019.07.023
In this commentary, I explain my perspective on the relationship between artificial intelligence (AI)/data science and biomedicine from a long-range retrospective view. The development of modern biomedicine has always been accelerated by the repeated emergence of new technologies. Since all life systems are basically governed by the information in their own DNA, information science has special importance for the study of biomedicine. Unlike in physics, no (or very few) leading laws have been found in biology. Thus, in biology, the "data-to-knowledge" approach is important. AI has historically been applied to biomedicine, and the recent news that an AI-based approach achieved the best performance in an international competition of protein structure prediction may be regarded as another landmark in the field. Similar approaches could contribute to solving problems in genome sequence interpretation, such as identifying cancer-driving mutations in the genome of patients. Recently, the explosive development of next-generation sequencing (NGS) has been producing massive data, and this trend will accelerate. NGS is not only used for "reading" DNA sequences, but also for obtaining various types of information at the single-cell level. These data can be regarded as grid data points in climate simulation. Both data science and AI will become essential for the integrative interpretation/simulation of these data, and will take a leading role in future precision medicine.
Keywords： Data science Artificial intelligence Next-generation sequencing DNA Cancer genome Single-cell transcriptomics
A Comparative Analysis of the Chloroplast Genomes of Four Salvia Medicinal Plants Article
Conglian Liang, Lei Wang, Juan Lei, Baozhong Duan, Weisi Ma, Shuiming Xiao, Haijun Qi, Zhen Wang, Yaoqi Liu, Xiaofeng Shen, Shuai Guo, Haoyu Hu, Jiang Xu, Shilin Chen
Engineering 2019, Volume 5, Issue 5, Pages 907-915 doi: 10.1016/j.eng.2019.01.017
Herbgenomics is an emerging field of traditional Chinese medicine (TCM) research and development. By combining TCM research with genomics, herbgenomics can help to establish the scientific validity of TCM and bring it into wider usage within the field of medicine. Salvia Linn. is a large genus of Labiatae that includes important medicinal plants. In this herbgenomics study, the complete chloroplast (cp) genomes of two Salvia (S.) spp.—namely, S. przewalskii and S. bulleyana, which are used as a surrogate for S. miltiorrhiza—were sequenced and compared with those of two other reported Salvia spp.—namely, S. miltiorrhiza and S. japonica. The genome organization, gene number, type, and repeat sequences were compared. The annotation results showed that both Salvia plants contain 114 unique genes, including 80 protein-coding, 30 transfer RNA (tRNA), and four ribosomal RNA (rRNA) genes. Repeat sequence analysis revealed 21 direct and 22 palindromic
sequences in both Salvia cp genomes, and 17 and 21 tandem repeats in S. przewalskii and S. bulleyana, respectively. A synteny comparison of the Salvia spp. cp genomes showed a high degree of sequence similarity in the coding regions and a relatively high divergence of the intergenic spacers. Pairwise alignment and singlenucleotide polymorphism (SNP) analyses found some candidate fragments to identify Salvia spp., such as the intergenic region of the trnV-ndhC, trnQ-rps16, atpI-atpH, psbA-ycf3, ycf1, rpoC2, ndhF, matK, rpoB, rpoA and accD genes. All of the results—including the repeat sequences and SNP sites, the inverted repeat (IR) region border, and the phylogenetic analysis—showed that S. przewalskii and S. bulleyana are extremely similar from a genetic standpoint. The cp genome sequences of the two Salvia spp. reported here will pave the way for breeding, species identification, phylogenetic evolution, and cp genetic engineering studies of Salvia medicinal plants.
Keywords： Salvia Chloroplast genome Comparative analysis
Reconstruction and Dynamics of the Human Intestinal Microbiome Observed In Situ Article
Xiaolin Liu, Min Dai, Yue Ma, Na Zhao, Ziyu Wang, Ying Yu, Yakun Xu, Huijie Zhang, Liyuan Xiang, He Tian, Guanghou Shui, Faming Zhang, Jun Wang
Engineering 2022, Volume 15, Issue 8, Pages 89-101 doi: 10.1016/j.eng.2021.03.015
The human gut microbiome has primarily been studied through the use of fecal samples, a practice that has generated vital knowledge on the composition and functional capacities of gastrointestinal microbial communities. However, this reliance on fecal materials limits the investigation of microbial dynamics in other locations along the gastrointestinal tract (in situ), and the infrequent availability of fecal samples prevents analysis at finer temporal scales (e.g., hours). In our study, we utilized colonic transendoscopic enteral tubing, a technology originally developed for fecal microbiota transplantation, to sample the ileocecal microbiome twice daily; metagenomic and metatranscriptomic analyses were then conducted on these samples. A total of 43 ileocecal and 28 urine and fecal samples were collected from five healthy volunteers. The ileocecal and fecal microbiomes, as profiled in the five volunteers, were found to be similar in metagenomic profiling, yet their active genes (metatranscriptome) were found to be highly distinct. Both microbiomes were perturbed after laxative exposure; over time, they exhibited reduced dissimilarity to their pre-treatment state, thereby demonstrating resilience as an innate property of the gut microbiome, although they did not fully recover within our observation time window. Sampling of the ileocecal microbiome during the day and at night revealed the existence of diurnal rhythms in a series of bacterial species and functional pathways, particularly those related to short-chain fatty acid production, such as Propionibacterium acnes and coenzyme A biosynthesis II. Autocorrelation analysis and fluctuations decomposition further indicated the significant periodicity of the diurnal oscillations. Metabolomic profiling in the fecal and urine samples mirrored the perturbance and recovery in the gut microbiome, indicating the crucial contribution of the gut microbiome to many key metabolites involved in host health. This study provides novel insights into the human gut microbiome and its inner resilience and diurnal rhythms, as well as the potential consequences of these to the host.
Keywords： Diurnal rhythm Reconstruction Metagenome Metatranscriptome Metabolome Transendoscopic enteral tubing
Alterations in the Gut Microbiome in Liver Recipients with Post-transplant Diabetes Mellitus Article
Qi Ling, Yuqiu Han, Yue Ma, Xiaosen Wang, Zheng Zhu, Jingyu Wang, Jiaying Cao, Lin Xiaohan, Jun Wang, Baohong Wang
Engineering 2023, Volume 31, Issue 12, Pages 98-111 doi: 10.1016/j.eng.2023.09.006
Post-transplant diabetes mellitus (PTDM) increases the risk of graft failure and death in liver transplant (LT) recipients. Experimental studies have indicated that enteric dysbiosis mediated by immunosuppressive tacrolimus (TAC) could contribute to glucose disorders, but no data on human recipients with PTDM have been reported. Here, by combining high-throughput shotgun metagenomics sequencing and metabolomics profiling, we characterized the intestinal microbiome (IM) in LT recipient cohort with or without PTDM and deciphered the potential relationship among IM, TAC dosage, and diabetes. By comparing with both non-PTDM and classical type 2 diabetes mellitus (T2DM), we identified microbial signatures of PTDM, which was characterized by the enriched Proteobacteria and decreased Bacteroidetes. Additionally, the altered microbes, as well as the microbial metabolomics, correlated with the dosage of TAC. Specifically, the levels of beneficial microbes associated with PTDM were lowered in recipients with the high TAC trough concentrations (> 5 ng∙mL–1) than those with low ones (< 5 ng∙mL–1), which was accompanied by reduced faecal metabolites involved in the biosynthesis of α-linolenic acid and arachidonic acid-lowering factors of developing T2DM. Moreover, these microbial signatures linked with the extent of glucose disorders in LT recipients. In summary, the faecal microbiome and metabolome differed between PTDM and non-PTDM patients, which were linked with TAC dosage. This study was the first to explore taxonomic alterations and bacterial gene functions to better understand the contribution of the IM to PTDM.
Keywords： Post-transplant diabetes mellitus Tacrolimus Metagenomics Metabolomics
Title Author Date Type Operation
Genomic Mutations within the Host Microbiome: Adaptive Evolution or Purifying Selection
Jiachao Zhang,Rob Knight,
Journal Article
Twelve Years of Genome-Wide Association Studies of Human Protein N-Glycosylation
Anna Timoshchuk, Sodbo Sharapov, Yurii S. Aulchenko
Journal Article
Development of a 50K SNP Array for Japanese Flounder and Its Application in Genomic Selection for Disease Resistance
Qian Zhou, Ya-dong Chen, Sheng Lu, Yang Liu, Wen-teng Xu, Yang-zhen Li, Lei Wang, Na Wang, Ying-ming Yang, Song-lin Chen
Journal Article
Extending the “Paracentral Dogma” of Biology with the Metabolome: Implications for Understanding Genomic–Glycomic–Metabolic–Epigenomic Synchronization
Albert Stuart Reece
Journal Article
Core Metabolic Features and Hot Origin of Bathyarchaeota
Xiaoyuan Feng, Yinzhao Wang, Rahul Zubin, Fengping Wang
Journal Article
Polar Animal Genetic Resources: Current Situation and Development Strategies
Chen Songlin, Xu Wenteng, Chen Zhangfan
Journal Article
Complete Genome Sequence of Shigella flexneri 2a 301 Strain and Analysis of “Shigella-islands”
Liu Hong,Yang Fan,Zhang Xiaobing,Zhang Jiyu,Yang Guowei,Dong Jie,Xue Ying,Hou Yunde,Yuan Zhenghong,Wen Yumei,Xu Jianguo,Cheng Hongsong,Ma Dalong,Wang Yu,Yang Jian,Shen Yan,Qiang Boqin,Wu Hongtao,Lü Weichuan,Jin Qi
Journal Article
Study on Family Collection, Gene Mapping, Gene Identification and Gene Function of Human Genetic Diseases
Xia Jiahui
Journal Article
A Comparative Analysis of the Chloroplast Genomes of Four Salvia Medicinal Plants
Conglian Liang, Lei Wang, Juan Lei, Baozhong Duan, Weisi Ma, Shuiming Xiao, Haijun Qi, Zhen Wang, Yaoqi Liu, Xiaofeng Shen, Shuai Guo, Haoyu Hu, Jiang Xu, Shilin Chen
Journal Article
Reconstruction and Dynamics of the Human Intestinal Microbiome Observed In Situ
Xiaolin Liu, Min Dai, Yue Ma, Na Zhao, Ziyu Wang, Ying Yu, Yakun Xu, Huijie Zhang, Liyuan Xiang, He Tian, Guanghou Shui, Faming Zhang, Jun Wang
Journal Article
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