Publications by authors named "Xiyin Wang"

99 Publications

Vaginal Squamous Cell Carcinoma Develops in Mice with Conditional Arid1a Loss and Gain of Oncogenic Kras Driven by Progesterone Receptor Cre.

Am J Pathol 2021 Apr 18. Epub 2021 Apr 18.

Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address:

Recent sequencing studies have found that loss-of-function mutations in ARID1A were enriched in gynecologic malignant tumors, and oncogenic KRAS mutations are a common finding in endometrial cancers. However, neither of these genetic insults alone was sufficient to develop gynecologic cancer. To determine the role of the combined effects of deletion of Arid1a and oncogenic Kras, Arid1a mice were crossed to Kras mice using progesterone receptor Cre (Pgr). Survival studies, histologic analysis, and immunohistochemistry were used to characterize the phenotype. Hormone dependence was evaluated by ovarian hormone depletion and estradiol replacement. Arid1a; Kras; Pgr mice experienced early euthanasia because of invasive vaginal squamous cell carcinoma. Younger mice had precancerous intraepithelial lesions. Immunohistochemistry supported the pathological diagnosis with abnormal expression and localization of cytokeratin 5, tumor protein P63, cyclin-dependent kinase inhibitor 2A, and marker of proliferation Ki-67. Ovarian hormone deletion in Arid1a; Kras; Pgr mice resulted in atrophic vaginal epithelium without evidence of vaginal tumors. Estradiol replacement in ovarian hormone-depleted Arid1a; Kras; Pgr mice resulted in lesions that resembled the squamous cell carcinoma in intact mice. This mouse can be used to study the transition from benign precursor lesions into invasive vaginal human papillomavirus-independent squamous cell carcinoma, offering insights into progression and pathogenesis of this rare disease.
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http://dx.doi.org/10.1016/j.ajpath.2021.03.013DOI Listing
April 2021

Coriander Genomics Database: a genomic, transcriptomic, and metabolic database for coriander.

Hortic Res 2020 Apr 1;7(1):55. Epub 2020 Apr 1.

Center for Genomics and Biocomputing/College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei, 063210, China.

Coriander (Coriandrum sativum L.), also known as cilantro, is a globally important vegetable and spice crop. Its genome and that of carrot are models for studying the evolution of the Apiaceae family. Here, we developed the Coriander Genomics Database (CGDB, http://cgdb.bio2db.com/) to collect, store, and integrate the genomic, transcriptomic, metabolic, functional annotation, and repeat sequence data of coriander and carrot to serve as a central online platform for Apiaceae and other related plants. Using these data sets in the CGDB, we intriguingly found that seven transcription factor (TF) families showed significantly greater numbers of members in the coriander genome than in the carrot genome. The highest ratio of the numbers of MADS TFs between coriander and carrot reached 3.15, followed by those for tubby protein (TUB) and heat shock factors. As a demonstration of CGDB applications, we identified 17 TUB family genes and conducted systematic comparative and evolutionary analyses. RNA-seq data deposited in the CGDB also suggest dose compensation effects of gene expression in coriander. CGDB allows bulk downloading, significance searches, genome browser analyses, and BLAST searches for comparisons between coriander and other plants regarding genomics, gene families, gene collinearity, gene expression, and the metabolome. A detailed user manual and contact information are also available to provide support to the scientific research community and address scientific questions. CGDB will be continuously updated, and new data will be integrated for comparative and functional genomic analysis in Apiaceae and other related plants.
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http://dx.doi.org/10.1038/s41438-020-0261-0DOI Listing
April 2020

Brassica carinata genome characterization clarifies U's triangle model of evolution and polyploidy in Brassica.

Plant Physiol 2021 Feb 4. Epub 2021 Feb 4.

Laboratory of Germplasm Innovation and Molecular Breeding, Institute of Vegetable Science, Zhejiang University, Hangzhou 310058, China.

Ethiopian mustard (Brassica carinata) in the Brassicaceae family possesses many excellent agronomic traits. Here, the high-quality genome sequence of B. carinata is reported. Characterization revealed a genome anchored to 17 chromosomes with a total length of 1.087 Gb and an N50 scaffold length of 60 Mb. Repetitive sequences account for approximately 634 Mb or 58.34% of the B. carinata genome. Notably, 51.91% of 97,149 genes are confined to the terminal 20% of chromosomes as a result of the expansion of repeats in pericentromeric regions. Brassica carinata shares one whole-genome triplication event with the five other species in U's triangle, a classic model of evolution and polyploidy in Brassica. Brassica carinata was deduced to have formed ∼0.047 Mya, which is slightly earlier than B. napus but later than B. juncea. Our analysis indicated that the relationship between the two subgenomes (BcaB and BcaC) is greater than that between other two tetraploid subgenomes (BjuB and BnaC) and their respective diploid parents. RNA-seq datasets and comparative genomic analysis were used to identify several key genes in pathways regulating disease resistance and glucosinolate metabolism. Further analyses revealed that genome triplication and tandem duplication played important roles in the expansion of those genes in Brassica species. With the genome sequencing of B. carinata completed, the genomes of all six Brassica species in U's triangle are now resolved. The data obtained from genome sequencing, transcriptome analysis, and comparative genomic efforts in this study provide valuable insights into the genome evolution of the six Brassica species in U's triangle.
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http://dx.doi.org/10.1093/plphys/kiab048DOI Listing
February 2021

Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment.

Biomedicines 2020 Nov 21;8(11). Epub 2020 Nov 21.

Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be of a specific diameter (~500 μm), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNFα stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment.
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http://dx.doi.org/10.3390/biomedicines8110525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700676PMC
November 2020

Paleo-polyploidization in Lycophytes.

Genomics Proteomics Bioinformatics 2020 06 4;18(3):333-340. Epub 2020 Nov 4.

Center for Computational Biology and Genomics, and School of Life Sciences, North China University of Science and Technology, Tangshan 063200, China; National Key Laboratory for North China Crop Improvement and Regulation, Agriculture University of Hebei, Baoding 071001, China. Electronic address:

Lycophytes and seed plants constitute the typical vascular plants. Lycophytes have been thought to have no paleo-polyploidization although the event is known to be critical for the fast expansion of seed plants. Here, genomic analyses including the homologous gene dot plot analysis detected multiple paleo-polyploidization events, with one occurring approximately 13-15 million years ago (MYA) and another about 125-142 MYA, during the evolution of the genome of Selaginella moellendorffii, a model lycophyte. In addition, comparative analysis of reconstructed ancestral genomes of lycophytes and angiosperms suggested that lycophytes were affected by more paleo-polyploidization events than seed plants. Results from the present genomic analyses indicate that paleo-polyploidization has contributed to the successful establishment of both lineages-lycophytes and seed plants-of vascular plants.
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http://dx.doi.org/10.1016/j.gpb.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801247PMC
June 2020

The celery genome sequence reveals sequential paleo-polyploidizations, karyotype evolution and resistance gene reduction in apiales.

Plant Biotechnol J 2021 04 18;19(4):731-744. Epub 2020 Nov 18.

School of Life Sciences/Center for Genomics and Bio-computing, North China University of Science and Technology, Tangshan, Hebei, China.

Celery (Apium graveolens L. 2n = 2x = 22), a member of the Apiaceae family, is among the most important and globally grown vegetables. Here, we report a high-quality genome sequence assembly, anchored to 11 chromosomes, with total length of 3.33 Gb and N50 scaffold length of 289.78 Mb. Most (92.91%) of the genome is composed of repetitive sequences, with 62.12% of 31 326 annotated genes confined to the terminal 20% of chromosomes. Simultaneous bursts of shared long-terminal repeats (LTRs) in different Apiaceae plants suggest inter-specific exchanges. Two ancestral polyploidizations were inferred, one shared by Apiales taxa and the other confined to Apiaceae. We reconstructed 8 Apiales proto-chromosomes, inferring their evolutionary trajectories from the eudicot common ancestor to extant plants. Transcriptome sequencing in three tissues (roots, leaves and petioles), and varieties with different-coloured petioles, revealed 4 and 2 key genes in pathways regulating anthocyanin and coumarin biosynthesis, respectively. A remarkable paucity of NBS disease-resistant genes in celery (62) and other Apiales was explained by extensive loss and limited production of these genes during the last ~10 million years, raising questions about their biotic defence mechanisms and motivating research into effects of chemicals, for example coumarins, that give off distinctive odours. Celery genome sequencing and annotation facilitates further research into important gene functions and breeding, and comparative genomic analyses in Apiales.
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http://dx.doi.org/10.1111/pbi.13499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051603PMC
April 2021

An updated explanation of ancestral karyotype changes and reconstruction of evolutionary trajectories to form Camelina sativa chromosomes.

BMC Genomics 2020 Oct 12;21(1):705. Epub 2020 Oct 12.

School of Life Sciences, North China University of Science and Technology, Tangshan, 063210, Hebei, China.

Background: Belonging to lineage I of Brassicaceae, Camelina sativa is formed by two hybridizations of three species (three sub-genomes). The three sub-genomes were diverged from a common ancestor, likely derived from lineage I (Ancestral Crucifer karyotype, ACK). The karyotype evolutionary trajectories of the C. sativa chromosomes are currently unknown. Here, we managed to adopt a telomere-centric theory proposed previously to explain the karyotype evolution in C. sativa.

Results: By characterizing the homology between A. lyrata and C. sativa chromosomes, we inferred ancestral diploid karyotype of C. sativa (ADK), including 7 ancestral chromosomes, and reconstructed the evolutionary trajectories leading to the formation of extant C. sativa genome. The process involved 2 chromosome fusions. We found that sub-genomes Cs-G1 and Cs-G2 may share a closer common ancestor than Cs-G3. Together with other lines of evidence from Arabidopsis, we propose that the Brassicaceae plants, even the eudicots, follow a chromosome fusion mechanism favoring end-end joining of different chromosomes, rather than a mechanism favoring the formation circular chromosomes and nested chromosome fusion preferred by the monocots.

Conclusions: The present work will contribute to understanding the formation of C. sativa chromosomes, providing insight into Brassicaceae karyotype evolution.
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http://dx.doi.org/10.1186/s12864-020-07081-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549213PMC
October 2020

Sequencing Multiple Cotton Genomes Reveals Complex Structures and Lays Foundation for Breeding.

Front Plant Sci 2020 16;11:560096. Epub 2020 Sep 16.

Center for Genomics and Computational Biology, North China University of Science and Technology, Tangshan, China.

Cotton is a major fiber plant, which provides raw materials for clothing, protecting humans from the harsh environment of cold or hot weathers, enriching the culture and custom of human societies. Due to its importance, the diploid and tetraploid genomes of different cotton plants have been repeatedly sequenced to obtain their complete and fine genome sequences. These valuable genome data sets revealed the evolutionary past of the cotton plants, which were recursively affected by polyploidization, with a decaploidization contributing to the formation of the genus , and a neo-tetraploidization contributing to the formation of nowadays widely cultivated cotton plants. Post-polyploidization genome instability resulted in numerous structural changes of the genomes, such as gene loss, DNA inversion and translocation, illegitimate recombination, and accumulation of repetitive sequences, and functional innovation accompanied by elevated evolutionary rates of genes. Many these changes have been asymmetric between subgnomes of the tetraploid cottons, rendering their divergent profiles of biological regulation and function. The availability of whole-genome sequences has now paved the way to identify and clone functional genes, e.g., those relating to fiber development, and to enhance breeding efforts to cultivate cottons to produce high-yield and high-quality fibers, and to resist environmental and biological stress.
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http://dx.doi.org/10.3389/fpls.2020.560096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525069PMC
September 2020

Illegitimate Recombination Between Homeologous Genes in Wheat Genome.

Front Plant Sci 2020 21;11:1076. Epub 2020 Jul 21.

School of Life Sciences, North China University of Science and Technology, Tangshan, China.

Polyploidies produce a large number of duplicated regions and genes in genomes, which have a long-term impact and stimulate genetic innovation. The high similarity between homeologous chromosomes, forming different subgenomes, or homologous regions after genome repatterning, may permit illegitimate DNA recombination. Here, based on gene colinearity, we aligned the (sub)genomes of common wheat (, AABBDD genotype) and its relatives, including (AA), (DD), and ssp. dicoccoides (AABB) to detect the homeologous (paralogous or orthologous) colinear genes within and between (sub)genomes. Besides, we inferred more ancient paralogous regions produced by a much ancient grass-common tetraploidization. By comparing the sequence similarity between paralogous and orthologous genes, we assumed abnormality in the topology of constructed gene trees, which could be explained by gene conversion as a result of illegitimate recombination. We found large numbers of inferred converted genes (>2,000 gene pairs) suggested long-lasting genome instability of the hexaploid plant, and preferential donor roles by DD genes. Though illegitimate recombination was much restricted, duplicated genes produced by an ancient whole-genome duplication, which occurred millions of years ago, also showed evidence of likely gene conversion. As to biological function, we found that ~40% catalytic genes in colinearity, including those involved in starch biosynthesis, were likely affected by gene conversion. The present study will contribute to understanding the functional and structural innovation of the common wheat genome.
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http://dx.doi.org/10.3389/fpls.2020.01076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396543PMC
July 2020

Pten and Dicer1 loss in the mouse uterus causes poorly differentiated endometrial adenocarcinoma.

Oncogene 2020 10 25;39(40):6286-6299. Epub 2020 Aug 25.

Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA.

Endometrial cancer remains the most common gynecological malignancy in the United States. While the loss of the tumor suppressor, PTEN (phosphatase and tensin homolog), is well studied in endometrial cancer, recent studies suggest that DICER1, the endoribonuclease responsible for miRNA genesis, also plays a significant role in endometrial adenocarcinoma. Conditional uterine deletion of Dicer1 and Pten in mice resulted in poorly differentiated endometrial adenocarcinomas, which expressed Napsin A and HNF1B (hepatocyte nuclear factor 1 homeobox B), markers of clear-cell adenocarcinoma. Adenocarcinomas were hormone-independent. Treatment with progesterone did not mitigate poorly differentiated adenocarcinoma, nor did it affect adnexal metastasis. Transcriptomic analyses of DICER1 deleted uteri or Ishikawa cells revealed unique transcriptomic profiles and global miRNA downregulation. Computational integration of miRNA with mRNA targets revealed deregulated let-7 and miR-16 target genes, similar to published human DICER1-mutant endometrial cancers from TCGA (The Cancer Genome Atlas). Similar to human endometrial cancers, tumors exhibited dysregulation of ephrin-receptor signaling and transforming growth factor-beta signaling pathways. LIM kinase 2 (LIMK2), an essential molecule in p21 signal transduction, was significantly upregulated and represents a novel mechanism for hormone-independent pathogenesis of endometrial adenocarcinoma. This preclinical mouse model represents the first genetically engineered mouse model of poorly differentiated endometrial adenocarcinoma.
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http://dx.doi.org/10.1038/s41388-020-01434-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541676PMC
October 2020

Reply to: Evaluating two different models of peanut's origin.

Nat Genet 2020 06 11;52(6):560-563. Epub 2020 May 11.

Center of Excellence in Genomics and Systems Biology, International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), Hyderabad, India.

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http://dx.doi.org/10.1038/s41588-020-0627-0DOI Listing
June 2020

Cotton Duplicated Genes Produced by Polyploidy Show Significantly Elevated and Unbalanced Evolutionary Rates, Overwhelmingly Perturbing Gene Tree Topology.

Front Genet 2020 23;11:239. Epub 2020 Apr 23.

School of Life Sciences, North China University of Science and Technology, Tangshan, China.

A phylogenetic tree can be used to illustrate the evolutionary relationship between a group of genes, especially duplicated genes, which are sources of genetic innovation and are often a hotspot of research. However, duplicated genes may have complex phylogenetic topologies due to changes in their evolutionary rates. Here, by constructing phylogenetic trees using different methods, we evaluated the phylogenetic relationships of duplicated genes produced by polyploidization in cotton. We found that at least 83.2% of phylogenetic trees did not conform the expected topology. Moreover, cotton homologous gene copy number has little effect on the topology of duplicated genes. Compared with their cacao orthologs, elevated evolutionary rates of cotton genes are responsible for distorted tree topology. Furthermore, as to both branch and site models, we inferred that positive natural selection during the divergence of fiber-development-related MYB genes was likely, and found that the reconstructed tree topology may often overestimate natural selection, as compared to the inference with the expected trees. Therefore, we emphasize the importance of borrowing precious information from gene collinearity in tree construction and evaluation, and have evidence to alert the citation of thousands of previous reports of adaptivity and functional innovation of duplicated genes.
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http://dx.doi.org/10.3389/fgene.2020.00239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190988PMC
April 2020

Coriander Genomics Database: a genomic, transcriptomic, and metabolic database for coriander.

Hortic Res 2020 1;7:55. Epub 2020 Apr 1.

1Center for Genomics and Biocomputing/College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei 063210 China.

Coriander ( L.), also known as cilantro, is a globally important vegetable and spice crop. Its genome and that of carrot are models for studying the evolution of the Apiaceae family. Here, we developed the Coriander Genomics Database (CGDB, http://cgdb.bio2db.com/) to collect, store, and integrate the genomic, transcriptomic, metabolic, functional annotation, and repeat sequence data of coriander and carrot to serve as a central online platform for Apiaceae and other related plants. Using these data sets in the CGDB, we intriguingly found that seven transcription factor (TF) families showed significantly greater numbers of members in the coriander genome than in the carrot genome. The highest ratio of the numbers of MADS TFs between coriander and carrot reached 3.15, followed by those for tubby protein (TUB) and heat shock factors. As a demonstration of CGDB applications, we identified 17 TUB family genes and conducted systematic comparative and evolutionary analyses. RNA-seq data deposited in the CGDB also suggest dose compensation effects of gene expression in coriander. CGDB allows bulk downloading, significance searches, genome browser analyses, and BLAST searches for comparisons between coriander and other plants regarding genomics, gene families, gene collinearity, gene expression, and the metabolome. A detailed user manual and contact information are also available to provide support to the scientific research community and address scientific questions. CGDB will be continuously updated, and new data will be integrated for comparative and functional genomic analysis in Apiaceae and other related plants.
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http://dx.doi.org/10.1038/s41438-020-0261-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109041PMC
April 2020

Prickly waterlily and rigid hornwort genomes shed light on early angiosperm evolution.

Nat Plants 2020 03 24;6(3):215-222. Epub 2020 Feb 24.

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education & State Key Laboratory of Hydraulics & Mountain River Engineering, College of Life Sciences, Sichuan University, Chengdu, China.

Angiosperms represent one of the most spectacular terrestrial radiations on the planet, but their early diversification and phylogenetic relationships remain uncertain. A key reason for this impasse is the paucity of complete genomes representing early-diverging angiosperms. Here, we present high-quality, chromosomal-level genome assemblies of two aquatic species-prickly waterlily (Euryale ferox; Nymphaeales) and the rigid hornwort (Ceratophyllum demersum; Ceratophyllales)-and expand the genomic representation for key sectors of the angiosperm tree of life. We identify multiple independent polyploidization events in each of the five major clades (that is, Nymphaeales, magnoliids, monocots, Ceratophyllales and eudicots). Furthermore, our phylogenomic analyses, which spanned multiple datasets and diverse methods, confirm that Amborella and Nymphaeales are successively sister to all other angiosperms. Furthermore, these genomes help to elucidate relationships among the major subclades within Mesangiospermae, which contain about 350,000 species. In particular, the species-poor lineage Ceratophyllales is supported as sister to eudicots, and monocots and magnoliids are placed as successively sister to Ceratophyllales and eudicots. Finally, our analyses indicate that incomplete lineage sorting may account for the incongruent phylogenetic placement of magnoliids between nuclear and plastid genomes.
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http://dx.doi.org/10.1038/s41477-020-0594-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075997PMC
March 2020

Sequential Paleotetraploidization shaped the carrot genome.

BMC Plant Biol 2020 Jan 31;20(1):52. Epub 2020 Jan 31.

Center for Genomics and Computational Biology, School of Life Sciences, North China University of Science and Technology, Tangshan, 063200, Hebei, China.

Background: Carrot (Daucus carota subsp. carota L.) is an important root crop with an available high-quality genome. The carrot genome is thought to have undergone recursive paleo-polyploidization, but the extent, occurrences, and nature of these events are not clearly defined.

Results: Using a previously published comparative genomics pipeline, we reanalysed the carrot genome and characterized genomic fractionation, as well as gene loss and retention, after each of the two tetraploidization events and inferred a dominant and sensitive subgenome for each event. In particular, we found strong evidence of two sequential tetraploidization events, with one (Dc-α) approximately 46-52 million years ago (Mya) and the other (Dc-β) approximately 77-87 Mya, both likely allotetraploidization in nature. The Dc-β event was likely common to all Apiales plants, occurring around the divergence of Apiales-Bruniales and after the divergence of Apiales-Asterales, likely playing an important role in the derivation and divergence of Apiales species. Furthermore, we found that rounds of polyploidy events contributed to the expansion of gene families responsible for plastidial methylerythritol phosphate (MEP), the precursor of carotenoid accumulation, and shaped underlying regulatory pathways. The alignment of orthologous and paralogous genes related to different events of polyploidization and speciation constitutes a comparative genomics platform for studying Apiales, Asterales, and many other related species.

Conclusions: Hierarchical inference of homology revealed two tetraploidization events that shaped the carrot genome, which likely contributed to the successful establishment of Apiales plants and the expansion of MEP, upstream of the carotenoid accumulation pathway.
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http://dx.doi.org/10.1186/s12870-020-2235-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995200PMC
January 2020

Low-Rate DoS Attacks Detection Based on MAF-ADM.

Sensors (Basel) 2019 Dec 29;20(1). Epub 2019 Dec 29.

College of Computer Science and Electronic Engineering, Hunan University, Changsha 410082, China.

Low-rate denial of service (LDoS) attacks reduce the quality of network service by sending periodical packet bursts to the bottleneck routers. It is difficult to detect by counter-DoS mechanisms due to its stealthy and low average attack traffic behavior. In this paper, we propose an anomaly detection method based on adaptive fusion of multiple features (MAF-ADM) for LDoS attacks. This study is based on the fact that the time-frequency joint distribution of the legitimate transmission control protocol (TCP) traffic would be changed under LDoS attacks. Several statistical metrics of the time-frequency joint distribution are chosen to generate isolation trees, which can simultaneously reflect the anomalies in time domain and frequency domain. Then we calculate anomaly score by fusing the results of all isolation trees according to their ability to isolate samples containing LDoS attacks. Finally, the anomaly score is smoothed by weighted moving average algorithm to avoid errors caused by noise in the network. Experimental results of Network Simulator 2 (NS2), testbed, and public datasets (WIDE2018 and LBNL) demonstrate that this method does detect LDoS attacks effectively with lower false negative rate.
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http://dx.doi.org/10.3390/s20010189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982801PMC
December 2019

Deciphering the high-quality genome sequence of coriander that causes controversial feelings.

Plant Biotechnol J 2020 06 5;18(6):1444-1456. Epub 2020 Feb 5.

School of Life Sciences, North China University of Science and Technology, Tangshan, Hebei, China.

Coriander (Coriandrum sativum L. 2n = 2x = 22), a plant from the Apiaceae family, also called cilantro or Chinese parsley, is a globally important crop used as vegetable, spice, fragrance and traditional medicine. Here, we report a high-quality assembly and analysis of its genome sequence, anchored to 11 chromosomes, with total length of 2118.68 Mb and N50 scaffold length of 160.99 Mb. We found that two whole-genome duplication events, respectively, dated to ~45-52 and ~54-61 million years ago, were shared by the Apiaceae family after their split from lettuce. Unbalanced gene loss and expression are observed between duplicated copies produced by these two events. Gene retention, expression, metabolomics and comparative genomic analyses of terpene synthase (TPS) gene family, involved in terpenoid biosynthesis pathway contributing to coriander's special flavour, revealed that tandem duplication contributed to coriander TPS gene family expansion, especially compared to their carrot counterparts. Notably, a TPS gene highly expressed in all 4 tissues and 3 development stages studied is likely a major-effect gene encoding linalool synthase and myrcene synthase. The present genome sequencing, transcriptome, metabolome and comparative genomic efforts provide valuable insights into the genome evolution and spice trait biology of Apiaceae and other related plants, and facilitated further research into important gene functions and crop improvement.
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http://dx.doi.org/10.1111/pbi.13310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206992PMC
June 2020

The wax gourd genomes offer insights into the genetic diversity and ancestral cucurbit karyotype.

Nat Commun 2019 11 14;10(1):5158. Epub 2019 Nov 14.

Key Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of Agriculture, Sino-Dutch Joint Laboratory of Horticultural Genomics, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

The botanical family Cucurbitaceae includes a variety of fruit crops with global or local economic importance. How their genomes evolve and the genetic basis of diversity remain largely unexplored. In this study, we sequence the genome of the wax gourd (Benincasa hispida), which bears giant fruit up to 80 cm in length and weighing over 20 kg. Comparative analyses of six cucurbit genomes reveal that the wax gourd genome represents the most ancestral karyotype, with the predicted ancestral genome having 15 proto-chromosomes. We also resequence 146 lines of diverse germplasm and build a variation map consisting of 16 million variations. Combining population genetics and linkage mapping, we identify a number of regions/genes potentially selected during domestication and improvement, some of which likely contribute to the large fruit size in wax gourds. Our analyses of these data help to understand genome evolution and function in cucurbits.
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http://dx.doi.org/10.1038/s41467-019-13185-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856369PMC
November 2019

Unique Molecular Features in High-Risk Histology Endometrial Cancers.

Cancers (Basel) 2019 Oct 27;11(11). Epub 2019 Oct 27.

Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Endometrial cancer is the most common gynecologic malignancy in the United States and the sixth most common cancer in women worldwide. Fortunately, most women who develop endometrial cancer have low-grade early-stage endometrioid carcinomas, and simple hysterectomy is curative. Unfortunately, 15% of women with endometrial cancer will develop high-risk histologic tumors including uterine carcinosarcoma or high-grade endometrioid, clear cell, or serous carcinomas. These high-risk histologic tumors account for more than 50% of deaths from this disease. In this review, we will highlight the biologic differences between low- and high-risk carcinomas with a focus on the cell of origin, early precursor lesions including atrophic and proliferative endometrium, and the potential role of stem cells. We will discuss treatment, including standard of care therapy, hormonal therapy, and precision medicine-based or targeted molecular therapies. We will also discuss the impact and need for model systems. The molecular underpinnings behind this high death to incidence ratio are important to understand and improve outcomes.
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http://dx.doi.org/10.3390/cancers11111665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896116PMC
October 2019

Polyploidy Index and Its Implications for the Evolution of Polyploids.

Front Genet 2019 10;10:807. Epub 2019 Sep 10.

School of Life Sciences, North China University of Science and Technology, Tangshan, China.

Polyploidy has contributed to the divergence and domestication of plants; however, estimation of the relative roles that different types of polyploidy have played during evolution has been difficult. Unbalanced and balanced gene removal was previously related to allopolyploidies and autopolyploidies, respectively. Here, to infer the types of polyploidies and evaluate their evolutionary effects, we devised a statistic, the Polyploidy-index or P-index, to characterize the degree of divergence between subgenomes of a polyploidy, to find whether there has been a balanced or unbalanced gene removal from the homoeologous regions. Based on a P-index threshold of 0.3 that distinguishes between known or previously inferred allo- or autopolyploidies, we found that 87.5% of 24 angiosperm paleo-polyploidies were likely produced by allopolyploidizations, responsible for establishment of major tribes such as Poaceae and Fabaceae, and large groups such as monocots and eudicots. These findings suggest that >99.7% of plant genomes likely derived directly from allopolyploidies, with autopolyploidies responsible for the establishment of only a few small genera, including , , and , each containing tens of species. Overall, these findings show that polyploids with high divergence between subgenomes (presumably allopolyploids) established the major plant groups, possibly through secondary contact between previously isolated populations and hybrid vigor associated with their re-joining.
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http://dx.doi.org/10.3389/fgene.2019.00807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746930PMC
September 2019

Alignment of Rutaceae Genomes Reveals Lower Genome Fractionation Level Than Eudicot Genomes Affected by Extra Polyploidization.

Front Plant Sci 2019 6;10:986. Epub 2019 Aug 6.

School of Life Sciences, North China University of Science and Technology, Tangshan, China.

Owing to their nutritional and commercial values, the genomes of several citrus plants have been sequenced, and the genome of one close relative in the Rutaceae family, atalantia (), has also been sequenced. Here, we show a family-level comparative analysis of Rutaceae genomes. By using grape as the outgroup and checking cross-genome gene collinearity, we systematically performed a hierarchical and event-related alignment of Rutaceae genomes, and produced a gene list defining homologous regions based on ancestral polyploidization or speciation. We characterized genome fractionation resulting from gene loss or relocation, and found that erosion of gene collinearity could largely be described by a geometric distribution. Moreover, we found that well-assembled Rutaceae genomes retained significantly more genes (65-82%) than other eudicots affected by recursive polyploidization. Additionally, we showed divergent evolutionary rates among Rutaceae plants, with sweet orange evolving faster than others, and by performing evolutionary rate correction, re-dated major evolutionary events during their evolution. We deduced that the divergence between the Rutaceae family and grape occurred about 81.15-91.74 million years ago (mya), while the split between citrus and atalantia plants occurred <10 mya. In addition, we showed that polyploidization led to a copy number expansion of key gene families contributing to the biosynthesis of vitamin C. Overall, the present effort provides an important comparative genomics resource and lays a foundation to understand the evolution and functional innovation of Rutaceae genomes.
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http://dx.doi.org/10.3389/fpls.2019.00986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691040PMC
August 2019

Aptamer-mediated N/Ce-doped carbon dots as a fluorescent and resonance Rayleigh scattering dual mode probe for arsenic(III).

Mikrochim Acta 2019 08 22;186(9):638. Epub 2019 Aug 22.

Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection (Guangxi Normal University), Ministry of Education, Guangxi Key Laboratory of Environmental Pollution Control Theory and Technology for Science and Education Combined with Science and Technology Innovation Base, Guilin, 541004, China.

Carbon dots doped with N/Ce, N/Eu and N/Tb were prepared by a microwave based hydrothermal technique. The fluorescence of the N/Ce co-doped carbon dots (CD) is strongest. They have excitation/emission maxima at 340/441 nm. CD was characterized by scanning electron microscopy, infrared and fluorescence spectroscopy. On addition of the nucleic acid aptamer (Apt) against arsenic(III) in pH 7 solution, the blue fluorescence of the doped carbon dots is partially quenched due to electrostatic interaction. On addition of As(III), it will bind to the aptamer, and the carbon dots are released. Hence, fluorescence becomes gradually restored. In addition, the resonance Rayleigh scattering signal (measured at 340 nm) is reduced. This dual-mode assay works in the 0.5-5.8 μg·L As(III) concentration range and has a 0.2 μg·L detection limit. Graphical abstract Schematic representation of fluorometric and resonance Rayleigh scattering dual mode analysis of As by using coupled Apt and CD probes. Apt: Aptamer. CD: Carbon dot. Flu: Fluorescence. RRS: Resonance Rayleigh scattering.
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http://dx.doi.org/10.1007/s00604-019-3764-3DOI Listing
August 2019

A novel N/Au co-doped carbon dot probe for continuous detection of silicate and phosphate by resonance Rayleigh scattering.

Analyst 2019 Aug;144(17):5090-5097

Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection (Guangxi Normal University), Ministry of Education; Guangxi Key Laboratory of Environmental Pollution Control Theory and Technology, Guilin 541004, China.

Co-doped carbon dots are new multifunctional carbon nanomaterials. Their fast preparation and new analytical applications such as in continuous detection and resonance Rayleigh scattering (RRS) probes are of interest to people. Herein, the N/Au co-doped carbon dots (CDN/Au) were prepared quickly by a microwave synthesis method using fructose as the carbon source and urea and HAuCl4 as dopants, and it exhibited an excellent RRS effect at 555 nm. Based on both silicate (SiO32-) and phosphate (PO43-) reacting with ammonium molybdate to form silicomolybdate heteropoly acid (SiMo) and phosphomolybdate heteropoly acid (PMo), PMo decomposed by the addition of citric acid, and SiMo/PMo combined with CDN/Au to show good RRS analytical properties, and a new strategy was developed to detect SiO32- and PO43- by the CDN/Au probes continuously. With the increase of SiO32- (PO43-), SiMo (PMo) reacted with CDN/Au probes to form more big particles which resulted in the RRS intensity enhancement at 555 nm, and had a good linear relationship with the SiO32- (PO43-) concentration in the range of 1.11 μg L-1-19.98 μg L-1, with detection limits of 0.3 μg L-1 SiO32- and 0.3 μg L-1 PO43-. Accordingly, a new RRS method was established for continuous detection of SiO32- and PO43- using CDN/Au as the probe.
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http://dx.doi.org/10.1039/c9an01072fDOI Listing
August 2019

The genome of cultivated peanut provides insight into legume karyotypes, polyploid evolution and crop domestication.

Nat Genet 2019 05 1;51(5):865-876. Epub 2019 May 1.

Center of Excellence in Genomics & Systems Biology, International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), Hyderabad, India.

High oil and protein content make tetraploid peanut a leading oil and food legume. Here we report a high-quality peanut genome sequence, comprising 2.54 Gb with 20 pseudomolecules and 83,709 protein-coding gene models. We characterize gene functional groups implicated in seed size evolution, seed oil content, disease resistance and symbiotic nitrogen fixation. The peanut B subgenome has more genes and general expression dominance, temporally associated with long-terminal-repeat expansion in the A subgenome that also raises questions about the A-genome progenitor. The polyploid genome provided insights into the evolution of Arachis hypogaea and other legume chromosomes. Resequencing of 52 accessions suggests that independent domestications formed peanut ecotypes. Whereas 0.42-0.47 million years ago (Ma) polyploidy constrained genetic variation, the peanut genome sequence aids mapping and candidate-gene discovery for traits such as seed size and color, foliar disease resistance and others, also providing a cornerstone for functional genomics and peanut improvement.
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http://dx.doi.org/10.1038/s41588-019-0402-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188672PMC
May 2019

Uterine Epithelial Development and Enhancer of Zeste Homolog 2: It Is Important for More than Just Cancer.

Am J Pathol 2019 06 13;189(6):1176-1177. Epub 2019 Apr 13.

Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address:

This commentary highlights the article by Fang et al that describes the role of enhancer of zeste homolog 2 in endometrial development.
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http://dx.doi.org/10.1016/j.ajpath.2019.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547055PMC
June 2019

Sequencing of Cultivated Peanut, Arachis hypogaea, Yields Insights into Genome Evolution and Oil Improvement.

Mol Plant 2019 07 19;12(7):920-934. Epub 2019 Mar 19.

South China Peanut Sub-center of National Center of Oilseed Crops Improvement, Guangdong Key Laboratory for Crops Genetic Improvement, Crops Research Institute, Guangdong Academy of Agricultural Sciences (GAAS), Guangzhou, China. Electronic address:

Cultivated peanut (Arachis hypogaea) is an allotetraploid crop planted in Asia, Africa, and America for edible oil and protein. To explore the origins and consequences of tetraploidy, we sequenced the allotetraploid A. hypogaea genome and compared it with the related diploid Arachis duranensis and Arachis ipaensis genomes. We annotated 39 888 A-subgenome genes and 41 526 B-subgenome genes in allotetraploid peanut. The A. hypogaea subgenomes have evolved asymmetrically, with the B subgenome resembling the ancestral state and the A subgenome undergoing more gene disruption, loss, conversion, and transposable element proliferation, and having reduced gene expression during seed development despite lacking genome-wide expression dominance. Genomic and transcriptomic analyses identified more than 2 500 oil metabolism-related genes and revealed that most of them show altered expression early in seed development while their expression ceases during desiccation, presenting a comprehensive map of peanut lipid biosynthesis. The availability of these genomic resources will facilitate a better understanding of the complex genome architecture, agronomically and economically important genes, and genetic improvement of peanut.
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http://dx.doi.org/10.1016/j.molp.2019.03.005DOI Listing
July 2019

Reconstruction of evolutionary trajectories of chromosomes unraveled independent genomic repatterning between Triticeae and Brachypodium.

BMC Genomics 2019 Mar 7;20(1):180. Epub 2019 Mar 7.

School of Life Sciences, North China University of Science and Technology, Tangshan, 063210, Hebei, China.

Background: After polyploidization, a genome may experience large-scale genome-repatterning, featuring wide-spread DNA rearrangement and loss, and often chromosome number reduction. Grasses share a common tetraploidization, after which the originally doubled chromosome numbers reduced to different chromosome numbers among them. A telomere-centric reduction model was proposed previously to explain chromosome number reduction. With Brachpodium as an intermediate linking different major lineages of grasses and a model plant of the Pooideae plants, we wonder whether it mediated the evolution from ancestral grass karyotype to Triticeae karyotype.

Results: By inferring the homology among Triticeae, rice, and Brachpodium chromosomes, we reconstructed the evolutionary trajectories of the Triticeae chromosomes. By performing comparative genomics analysis with rice as a reference, we reconstructed the evolutionary trajectories of Pooideae plants, including Ae. Tauschii (2n = 14, DD), barley (2n = 14), Triticum turgidum (2n = 4x = 28, AABB), and Brachypodium (2n = 10). Their extant Pooidea and Brachypodium chromosomes were independently produced after sequential nested chromosome fusions in the last tens of millions of years, respectively, after their split from rice. More frequently than would be expected by chance, in Brachypodium, the 'invading' and 'invaded' chromosomes are homoeologs, originating from duplication of a common ancestral chromosome, that is, with more extensive DNA-level correspondence to one another than random chromosomes, nested chromosome fusion events between homoeologs account for three of seven cases in Brachypodium (P-value≈0.00078). However, this phenomenon was not observed during the formation of other Pooideae chromosomes.

Conclusions: Notably, we found that the Brachypodium chromosomes formed through exclusively distinctive trajectories from those of Pooideae plants, and were well explained by the telomere-centric model. Our work will contribute to understanding the structural and functional innovation of chromosomes in different Pooideae lineages and beyond.
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http://dx.doi.org/10.1186/s12864-019-5566-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407190PMC
March 2019

Gene duplication and genetic innovation in cereal genomes.

Genome Res 2019 02 16;29(2):261-269. Epub 2019 Jan 16.

Plant Genome Mapping Laboratory, University of Georgia, Athens, Georgia 30602, USA.

Organisms continuously require genetic variation to adapt to fluctuating environments, yet major evolutionary events are episodic, making the relationship between genome evolution and organismal adaptation of considerable interest. Here, by genome-wide comparison of sorghum, maize, and rice SNPs, we investigated reservoirs of genetic variations with high precision. For sorghum and rice, which have not experienced whole-genome duplication in 96 million years or more, tandem duplicates accumulate relatively more SNPs than paralogous genes retained from genome duplication. However, maize, which experienced lineage-specific genome duplication and has a relatively larger supply of paralogous duplicates, shows SNP enrichment in paralogous genes. The proportion of genes showing signatures of recent positive selection is higher in small-scale (tandem and transposed) than genome-scale duplicates in sorghum, but the opposite is true in maize. A large proportion of recent duplications in rice are species-specific; however, most recent duplications in sorghum are derived from ancestral gene families. A new retrotransposon family was also a source of many recent sorghum duplications, illustrating a role in providing variation for genetic innovations. This study shows that diverse evolutionary mechanisms provide the raw genetic material for adaptation in taxa with divergent histories of genome evolution.
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http://dx.doi.org/10.1101/gr.237511.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360818PMC
February 2019

Discovery and annotation of a novel transposable element family in Gossypium.

BMC Plant Biol 2018 Nov 28;18(1):307. Epub 2018 Nov 28.

State Key Laboratory of Cotton Biology, Institute of Cotton Research of Chinese Academy of Agricultural Science, Anyang, 455000, Henan, China.

Background: Fluorescence in situ hybridization (FISH) is an efficient cytogenetic technology to study chromosome structure. Transposable element (TE) is an important component in eukaryotic genomes and can provide insights in the structure and evolution of eukaryotic genomes.

Results: A FISH probe derived from bacterial artificial chromosome (BAC) clone 299N22 generated striking signals on all 26 chromosomes of the cotton diploid A genome (AA, 2x=26) but very few on the diploid D genome (DD, 2x=26). All 26 chromosomes of the A sub genome (At) of tetraploid cotton (AADD, 2n=4x=52) also gave positive signals with this FISH probe, whereas very few signals were observed on the D sub genome (Dt). Sequencing and annotation of BAC clone 299N22, revealed a novel Ty3/gypsy transposon family, which was named as 'CICR'. This family is a significant contributor to size expansion in the A (sub) genome but not in the D (sub) genome. Further FISH analysis with the LTR of CICR as a probe revealed that CICR is lineage-specific, since massive repeats were found in A and B genomic groups, but not in C-G genomic groups within the Gossypium genus. Molecular evolutionary analysis of CICR suggested that tetraploid cottons evolved after silence of the transposon family 1-1.5 million years ago (Mya). Furthermore, A genomes are more homologous with B genomes, and the C, E, F, and G genomes likely diverged from a common ancestor prior to 3.5-4 Mya, the time when CICR appeared. The genomic variation caused by the insertion of CICR in the A (sub) genome may have played an important role in the speciation of organisms with A genomes.

Conclusions: The CICR family is highly repetitive in A and B genomes of Gossypium, but not amplified in the C-G genomes. The differential amount of CICR family in At and Dt will aid in partitioning sub genome sequences for chromosome assemblies during tetraploid genome sequencing and will act as a method for assessing the accuracy of tetraploid genomes by looking at the proportion of CICR elements in resulting pseudochromosome sequences. The timeline of the expansion of CICR family provides a new reference for cotton evolutionary analysis, while the impact on gene function caused by the insertion of CICR elements will be a target for further analysis of investigating phenotypic differences between A genome and D genome species.
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http://dx.doi.org/10.1186/s12870-018-1519-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264596PMC
November 2018

Recursive Paleohexaploidization Shaped the Durian Genome.

Plant Physiol 2019 01 1;179(1):209-219. Epub 2018 Nov 1.

Center for Genomics and Computational Biology, North China University of Science and Technology, Caofeidian Dist., Tangshan, Hebei, China 063210.

The durian () genome has recently become available, and analysis of this genome reveals two paleopolyploidization events previously inferred as shared with cotton ( spp.). Here, we reanalyzed the durian genome in comparison with other well-characterized genomes. We found that durian and cotton were actually affected by different polyploidization events: hexaploidization in durian ∼19-21 million years ago (mya) and decaploidization in cotton ∼13-14 mya. Previous interpretations of shared polyploidization events may have resulted from the elevated evolutionary rates in cotton genes due to the decaploidization and insufficient consideration of the complexity of plant genomes. The decaploidization elevated evolutionary rates of cotton genes by ∼64% compared to durian and explained a previous ∼4-fold over dating of the event. In contrast, the hexaploidization in durian did not prominently elevate gene evolutionary rates, likely due to its long generation time. Moreover, divergent evolutionary rates probably explain 98.4% of reconstructed phylogenetic trees of homologous genes being incongruent with expected topology. The findings provide further insight into the roles played by polypoidization in the evolution of genomes and genes, and they suggest revisiting existing reconstructed phylogenetic trees.
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http://dx.doi.org/10.1104/pp.18.00921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324235PMC
January 2019