Publications by authors named "Kirill Borziak"

19 Publications

  • Page 1 of 1

Identification of Liver Cancer Stem Cell Stemness Markers Using a Comparative Analysis of Public Data Sets.

Stem Cells Cloning 2021 16;14:9-17. Epub 2021 Jun 16.

Center for Biomedical and Population Health Informatics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Purpose: Comparative reanalysis of single-cell transcriptomics data to gain useful novel insights into cancer stem cells (CSCs), which are a rare subset of cells within tumors, characterized by their capability to self-renew and differentiate, and their role in tumorigenicity.

Patients And Methods: This project utilized publically available liver single-cell RNA-seq datasets of liver cancer and liver progenitor cell types to demonstrate how shared large amounts of data can generate new and valuable information. The data were analyzed using EdgeR differential expression analysis, with focus on a set of 34 known stemness markers.

Results: We showed that the expression of stemness markers SOX9, KRT19, KRT7, and CD24, and Yamanaka factors Oct4 and SOX2 in CSCs was significantly elevated relative to progenitor cell types, potentially explaining their increased differentiation and replication potential.

Conclusion: These results help to further document the complementary expression changes that give CSCs their distinct phenotypic profile. Our findings have potential significance to advance our knowledge of the important genes relevant to CSCs.
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http://dx.doi.org/10.2147/SCCAA.S307043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216768PMC
June 2021

ReMeDy: a platform for integrating and sharing published stem cell research data with a focus on iPSC trials.

Database (Oxford) 2021 Jun;2021

Center for Biomedical and Population Health Informatics, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Icahn L2-36, New York, NY 10029, USA.

Abstract: Recent regenerative medicine studies have emphasized the need for increased standardization, harmonization and sharing of information related to stem cell product characterization, to help drive these innovative interventions toward public availability and to increase collaboration in the scientific community. Although numerous attempts and numerous databases have been made to manage these data, a platform that incorporates all the heterogeneous data collected from stem cell projects into a harmonized project-based framework is still lacking. The aim of the database, which is described in this study, is to provide an intelligent informatics solution that integrates comprehensive characterization of diverse stem cell product characteristics with research subject and project outcome information. In the resulting platform, heterogeneous data are validated using predefined ontologies and stored in a relational database, to ensure data quality and ease of access. Testing was performed using 51 published, publically available induced pluripotent stem cell projects conducted in clinical, preclinical and in-vitro evaluations. Future aims of this project include further increasing the database size to include all published stem cell trials and develop additional data visualization tools to improve usability. Our testing demonstrated the robustness of the proposed platform, by seamlessly harmonizing diverse common data elements, and the potential of this platform for driving knowledge generation from the aggregation and harmonization of these diverse data.

Database Url: https://remedy.mssm.edu/.
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http://dx.doi.org/10.1093/database/baab038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218701PMC
June 2021

Introducing a Platform for Integrating and Sharing Stem Cell Research Data.

Stud Health Technol Inform 2021 May;281:387-391

Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Advancements in regenerative medicine have highlighted the need for increased standardization and sharing of stem cell products to help drive these innovative interventions toward public availability and to increase collaboration in the scientific community. Although numerous attempts and numerous databases have been made to store this data, there is still a lack of a platform that incorporates heterogeneous stem cell information into a harmonized project-based framework. The aim of the platform described in this study, ReMeDy, is to provide an intelligent informatics solution which integrates diverse stem cell product characteristics with study subject and omics information. In the resulting platform, heterogeneous data is validated using predefined ontologies and stored in a relational database. In this initial feasibility study, testing of the ReMeDy functionality was performed using published, publically-available induced pluripotent stem cell projects conducted in in vitro, preclinical and intervention evaluations. It demonstrated the robustness of ReMeDy for storing diverse iPSC data, by seamlessly harmonizing diverse common data elements, and the potential utility of this platform for driving knowledge generation from the aggregation of this shared data. Next steps include increasing the number of curated projects by developing a crowdsourcing framework for data upload and an automated pipeline for metadata abstraction. The database is publically accessible at https://remedy.mssm.edu/.
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http://dx.doi.org/10.3233/SHTI210186DOI Listing
May 2021

Comparative Analysis of Public Data Sets to Identify Stemness Markers That Differentiate Liver Cancer Stem Cells.

Stud Health Technol Inform 2021 May;281:818-819

Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Cancer stem cells (CSCs) represent an important field in translational medicine for generating novel cancer treatments. To identify important stemness markers in liver CSCs that potentially explain their resistance to treatment, we analyzed 10865 single-cell RNA-seq samples across 42684 coding and non-coding genes. Our results show that CSCs have significantly increased expression of two Yamanaka factors (Oct4, 2.14X and SOX2, 1.13X) and three stemness factors (CD44, 3.25X; KRT7, 2.2X; SOX9, 1.71X), relative to liver progenitor cells. Our study demonstrates the potential power of harnessing shared big data for driving translational medicine for novel hypothesis generation.
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http://dx.doi.org/10.3233/SHTI210290DOI Listing
May 2021

Drosophila female reproductive tract gene expression reveals coordinated mating responses and rapidly evolving tissue-specific genes.

G3 (Bethesda) 2021 04;11(3)

Center for Reproductive Evolution, Biology Department, Syracuse University, Syracuse, NY, USA.

Sexual reproduction in internally fertilizing species requires complex coordination between female and male reproductive systems and among the diverse tissues of the female reproductive tract (FRT). Here, we report a comprehensive, tissue-specific investigation of Drosophila melanogaster FRT gene expression before and after mating. We identified expression profiles that distinguished each tissue, including major differences between tissues with glandular or primarily nonglandular epithelium. All tissues were enriched for distinct sets of genes possessing secretion signals that exhibited accelerated evolution, as might be expected for genes participating in molecular interactions between the sexes within the FRT extracellular environment. Despite robust transcriptional differences between tissues, postmating responses were dominated by coordinated transient changes indicative of an integrated systems-level functional response. This comprehensive characterization of gene expression throughout the FRT identifies putative female contributions to postcopulatory events critical to reproduction and potentially reproductive isolation, as well as the putative targets of sexual selection and conflict.
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http://dx.doi.org/10.1093/g3journal/jkab020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063083PMC
April 2021

Ovarian fluid proteome variation associates with sperm swimming speed in an externally fertilizing fish.

J Evol Biol 2020 12 25;33(12):1783-1794. Epub 2020 Oct 25.

Department of Anatomy, University of Otago, Dunedin, New Zealand.

Sperm velocity is a key trait that predicts the outcome of sperm competition. By promoting or impeding sperm velocity, females can control fertilization via postcopulatory cryptic female choice. In Chinook salmon, ovarian fluid (OF), which surrounds the ova, mediates sperm velocity according to male and female identity, biasing the outcome of sperm competition towards males with faster sperm. Past investigations have revealed proteome variation in OF, but the specific components of OF that differentially mediate sperm velocity have yet to be characterized. Here we use quantitative proteomics to investigate whether OF protein composition explains variation in sperm velocity and fertilization success. We found that OF proteomes from six females robustly clustered into two groups and that these groups are distinguished by the abundance of a restricted set of proteins significantly associated with sperm velocity. Exposure of sperm to OF from females in group I had faster sperm compared to sperm exposed to the OF of group II females. Overall, OF proteins that distinguished between these groups were enriched for vitellogenin and calcium ion interactions. Our findings suggest that these proteins may form the functional basis for cryptic female choice via the biochemical and physiological mediation of sperm velocity.
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http://dx.doi.org/10.1111/jeb.13717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719593PMC
December 2020

Towards Intelligent Integration and Sharing of Stem Cell Research Data.

Stud Health Technol Inform 2020 Jun;272:334-337

Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA.

Advancements in regenerative medicine have brought to the fore the need for increased standardization and sharing of stem cell product characterization to help drive these innovative interventions toward public availability. Although numerous attempts have been made to store this data, there is still a lack of a platform that incorporates heterogeneous stem cell information into a harmonized project-based framework. The aim of this project was to introduce and pilot-test an intelligent informatics solution which integrates diverse stem cell product characteristics with study subject and omics information. In the resulting platform, heterogeneous data is validated using predefined ontologies and stored in a NoSQL repository. Pilot-testing was performed on nine sponsored stem cell projects conducting preclinical and intervention evaluations. The pilot-testing demonstrated the robustness of the proposed platform, by seamlessly harmonizing diverse common data elements, and the potential of this platform for driving knowledge generation from the aggregation of this shared data.
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http://dx.doi.org/10.3233/SHTI200563DOI Listing
June 2020

Molecular Diversification of the Seminal Fluid Proteome in a Recently Diverged Passerine Species Pair.

Mol Biol Evol 2020 02;37(2):488-506

Center for Reproductive Evolution, Department of Biology, Syracuse University, Syracuse, NY.

Seminal fluid proteins (SFPs) mediate an array of postmating reproductive processes that influence fertilization and fertility. As such, it is widely held that SFPs may contribute to postmating, prezygotic reproductive barriers between closely related taxa. We investigated seminal fluid (SF) diversification in a recently diverged passerine species pair (Passer domesticus and Passer hispaniolensis) using a combination of proteomic and comparative evolutionary genomic approaches. First, we characterized and compared the SF proteome of the two species, revealing consistencies with known aspects of SFP biology and function in other taxa, including the presence and diversification of proteins involved in immunity and sperm maturation. Second, using whole-genome resequencing data, we assessed patterns of genomic differentiation between house and Spanish sparrows. These analyses detected divergent selection on immunity-related SF genes and positive selective sweeps in regions containing a number of SF genes that also exhibited protein abundance diversification between species. Finally, we analyzed the molecular evolution of SFPs across 11 passerine species and found a significantly higher rate of positive selection in SFPs compared with the rest of the genome, as well as significant enrichments for functional pathways related to immunity in the set of positively selected SF genes. Our results suggest that selection on immunity pathways is an important determinant of passerine SF composition and evolution. Assessing the role of immunity genes in speciation in other recently diverged taxa should be prioritized given the potential role for immunity-related proteins in reproductive incompatibilities in Passer sparrows.
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http://dx.doi.org/10.1093/molbev/msz235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993853PMC
February 2020

Female novelty and male status dynamically modulate ejaculate expenditure and seminal fluid proteome over successive matings in red junglefowl.

Sci Rep 2019 04 10;9(1):5852. Epub 2019 Apr 10.

Edward Grey Institute, Department of Zoology, University of Oxford, Oxford, OX1 3SZ, UK.

Theory predicts that males will strategically invest in ejaculates according to the value of mating opportunities. While strategic sperm allocation has been studied extensively, little is known about concomitant changes in seminal fluid (SF) and its molecular composition, despite increasing evidence that SF proteins (SFPs) are fundamental in fertility and sperm competition. Here, we show that in male red junglefowl, Gallus gallus, along with changes in sperm numbers and SF investment, SF composition changed dynamically over successive matings with a first female, immediately followed by mating with a second, sexually novel female. The SF proteome exhibited a pattern of both protein depletion and enrichment over successive matings, including progressive increases in immunity and plasma proteins. Ejaculates allocated to the second female had distinct proteomic profiles, where depletion of many SFPs was compensated by increased investment in others. This response was partly modulated by male social status: when mating with the second, novel female, subdominants (but not dominants) preferentially invested in SFPs associated with sperm composition, which may reflect status-specific differences in mating rates, sperm maturation and sperm competition. Global proteomic SF analysis thus reveals that successive matings trigger rapid, dynamic SFP changes driven by a combination of depletion and strategic allocation.
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http://dx.doi.org/10.1038/s41598-019-41336-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458113PMC
April 2019

Proteins, Transcripts, and Genetic Architecture of Seminal Fluid and Sperm in the Mosquito .

Mol Cell Proteomics 2019 03 14;18(Suppl 1):S6-S22. Epub 2018 Dec 14.

Center for Reproductive Evolution, Syracuse University, Syracuse, New York. Electronic address:

The yellow fever mosquito, , transmits several viruses causative of serious diseases, including dengue, Zika, and chikungunya. Some proposed efforts to control this vector involve manipulating reproduction to suppress wild populations or to replace them with disease-resistant mosquitoes. The design of such strategies requires an intimate knowledge of reproductive processes, yet our basic understanding of reproductive genetics in this vector remains largely incomplete. To accelerate future investigations, we have comprehensively catalogued sperm and seminal fluid proteins (SFPs) transferred to females in the ejaculate using tandem mass spectrometry. By excluding female-derived proteins using an isotopic labeling approach, we identified 870 sperm proteins and 280 SFPs. Functional composition analysis revealed parallels with known aspects of sperm biology and SFP function in other insects. To corroborate our proteome characterization, we also generated transcriptomes for testes and the male accessory glands-the primary contributors to , sperm and seminal fluid, respectively. Differential gene expression of accessory glands from virgin and mated males suggests that transcripts encoding proteins involved in protein translation are upregulated post-mating. Several SFP transcripts were also modulated after mating, but >90% remained unchanged. Finally, a significant enrichment of SFPs was observed on chromosome 1, which harbors the male sex determining locus in this species. Our study provides a comprehensive proteomic and transcriptomic characterization of ejaculate production and composition and thus provides a foundation for future investigations of , reproductive biology, from functional analysis of individual proteins to broader examination of reproductive processes.
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http://dx.doi.org/10.1074/mcp.RA118.001067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427228PMC
March 2019

Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans.

PLoS Genet 2018 02 15;14(2):e1007219. Epub 2018 Feb 15.

Department of Biology, Syracuse University, Syracuse, NY, United States of America.

Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite ("seesaw") transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome.
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http://dx.doi.org/10.1371/journal.pgen.1007219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831748PMC
February 2018

Contrasting patterns of evolutionary constraint and novelty revealed by comparative sperm proteomic analysis in Lepidoptera.

BMC Genomics 2017 Dec 2;18(1):931. Epub 2017 Dec 2.

Center for Reproductive Evolution, Department of Biology, Syracuse University, Syracuse, NY, USA.

Background: Rapid evolution is a hallmark of reproductive genetic systems and arises through the combined processes of sequence divergence, gene gain and loss, and changes in gene and protein expression. While studies aiming to disentangle the molecular ramifications of these processes are progressing, we still know little about the genetic basis of evolutionary transitions in reproductive systems. Here we conduct the first comparative analysis of sperm proteomes in Lepidoptera, a group that exhibits dichotomous spermatogenesis, in which males produce a functional fertilization-competent sperm (eupyrene) and an incompetent sperm morph lacking nuclear DNA (apyrene). Through the integrated application of evolutionary proteomics and genomics, we characterize the genomic patterns potentially associated with the origination and evolution of this unique spermatogenic process and assess the importance of genetic novelty in Lepidopteran sperm biology.

Results: Comparison of the newly characterized Monarch butterfly (Danaus plexippus) sperm proteome to those of the Carolina sphinx moth (Manduca sexta) and the fruit fly (Drosophila melanogaster) demonstrated conservation at the level of protein abundance and post-translational modification within Lepidoptera. In contrast, comparative genomic analyses across insects reveals significant divergence at two levels that differentiate the genetic architecture of sperm in Lepidoptera from other insects. First, a significant reduction in orthology among Monarch sperm genes relative to the remainder of the genome in non-Lepidopteran insect species was observed. Second, a substantial number of sperm proteins were found to be specific to Lepidoptera, in that they lack detectable homology to the genomes of more distantly related insects. Lastly, the functional importance of Lepidoptera specific sperm proteins is broadly supported by their increased abundance relative to proteins conserved across insects.

Conclusions: Our results identify a burst of genetic novelty amongst sperm proteins that may be associated with the origin of heteromorphic spermatogenesis in ancestral Lepidoptera and/or the subsequent evolution of this system. This pattern of genomic diversification is distinct from the remainder of the genome and thus suggests that this transition has had a marked impact on lepidopteran genome evolution. The identification of abundant sperm proteins unique to Lepidoptera, including proteins distinct between specific lineages, will accelerate future functional studies aiming to understand the developmental origin of dichotomous spermatogenesis and the functional diversification of the fertilization incompetent apyrene sperm morph.
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http://dx.doi.org/10.1186/s12864-017-4293-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712127PMC
December 2017

Comparative Sperm Proteomics in Mouse Species with Divergent Mating Systems.

Mol Biol Evol 2017 06;34(6):1403-1416

Department of Biology, Syracuse University, Syracuse, NY.

Sexual selection is the pervasive force underlying the dramatic divergence of sperm form and function. Although it has been demonstrated that testis gene expression evolves rapidly, exploration of the proteomic basis of sperm diversity is in its infancy. We have employed a whole-cell proteomics approach to characterize sperm divergence among closely related Mus species that experience different sperm competition regimes and exhibit pronounced variation in sperm energetics, motility and fertilization capacity. Interspecific comparisons revealed significant abundance differences amongst proteins involved in fertilization capacity, including those that govern sperm-zona pellucida interactions, axoneme components and metabolic proteins. Ancestral reconstruction of relative testis size suggests that the reduction of zona pellucida binding proteins and heavy-chain dyneins was associated with a relaxation in sperm competition in the M. musculus lineage. Additionally, the decreased reliance on ATP derived from glycolysis in high sperm competition species was reflected in abundance decreases in glycolytic proteins of the principle piece in M. spretus and M. spicilegus. Comparison of protein abundance and stage-specific testis expression revealed a significant correlation during spermatid development when dynamic morphological changes occur. Proteins underlying sperm diversification were also more likely to be subject to translational repression, suggesting that sperm composition is influenced by the evolution of translation control mechanisms. The identification of functionally coherent classes of proteins relating to sperm competition highlights the utility of evolutionary proteomic analyses and reveals that both intensified and relaxed sperm competition can have a pronounced impact on the molecular composition of the male gamete.
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http://dx.doi.org/10.1093/molbev/msx084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435083PMC
June 2017

The Seminal fluid proteome of the polyandrous Red junglefowl offers insights into the molecular basis of fertility, reproductive ageing and domestication.

Sci Rep 2016 11 2;6:35864. Epub 2016 Nov 2.

Center for Reproductive Evolution, Department of Biology, Syracuse University, US.

Seminal fluid proteins (SFPs) are emerging as fundamental contributors to sexual selection given their role in post-mating reproductive events, particularly in polyandrous species where the ejaculates of different males compete for fertilisation. SFP identification however remains taxonomically limited and little is known about avian SFPs, despite extensive work on sexual selection in birds. We characterize the SF proteome of the polyandrous Red junglefowl, Gallus gallus, the wild species that gave rise to the domestic chicken. We identify 1,141 SFPs, including proteins involved in immunity and antimicrobial defences, sperm maturation, and fertilisation, revealing a functionally complex SF proteome. This includes a predominant contribution of blood plasma proteins that is conserved with human SF. By comparing the proteome of young and old males with fast or slow sperm velocity in a balanced design, we identify proteins associated with ageing and sperm velocity, and show that old males that retain high sperm velocity have distinct proteome characteristics. SFP comparisons with domestic chickens revealed both qualitative and quantitative differences likely associated with domestication and artificial selection. Collectively, these results shed light onto the functional complexity of avian SF, and provide a platform for molecular studies of fertility, reproductive ageing, and domestication.
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http://dx.doi.org/10.1038/srep35864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090203PMC
November 2016

Characterisation of the Manduca sexta sperm proteome: Genetic novelty underlying sperm composition in Lepidoptera.

Insect Biochem Mol Biol 2015 Jul 28;62:183-93. Epub 2015 Feb 28.

Department of Biology, Syracuse University, Syracuse, NY, USA. Electronic address:

The application of mass spectrometry based proteomics to sperm biology has greatly accelerated progress in understanding the molecular composition and function of spermatozoa. To date, these approaches have been largely restricted to model organisms, all of which produce a single sperm morph capable of oocyte fertilisation. Here we apply high-throughput mass spectrometry proteomic analysis to characterise sperm composition in Manduca sexta, the tobacco hornworm moth, which produce heteromorphic sperm, including one fertilisation competent (eupyrene) and one incompetent (apyrene) sperm type. This resulted in the high confidence identification of 896 proteins from a co-mixed sample of both sperm types, of which 167 are encoded by genes with strict one-to-one orthology in Drosophila melanogaster. Importantly, over half (55.1%) of these orthologous proteins have previously been identified in the D. melanogaster sperm proteome and exhibit significant conservation in quantitative protein abundance in sperm between the two species. Despite the complex nature of gene expression across spermatogenic stages, a significant correlation was also observed between sperm protein abundance and testis gene expression. Lepidopteran-specific sperm proteins (e.g., proteins with no homology to proteins in non-Lepidopteran taxa) were present in significantly greater abundance on average than those with homology outside the Lepidoptera. Given the disproportionate production of apyrene sperm (96% of all mature sperm in Manduca) relative to eupyrene sperm, these evolutionarily novel and highly abundant proteins are candidates for possessing apyrene-specific functions. Lastly, comparative genomic analyses of testis-expressed, ovary-expressed and sperm genes identified a concentration of novel sperm proteins shared amongst Lepidoptera of potential relevance to the evolutionary origin of heteromorphic spermatogenesis. As the first published Lepidopteran sperm proteome, this whole-cell proteomic characterisation will facilitate future evolutionary genetic and developmental studies of heteromorphic sperm production and parasperm function. Furthermore, the analyses presented here provide useful annotation information regarding sex-biased gene expression, novel Lepidopteran genes and gene function in the male gamete to complement the newly sequenced and annotated Manduca genome.
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http://dx.doi.org/10.1016/j.ibmb.2015.02.011DOI Listing
July 2015

Comparative genomic analysis reveals 2-oxoacid dehydrogenase complex lipoylation correlation with aerobiosis in archaea.

PLoS One 2014 28;9(1):e87063. Epub 2014 Jan 28.

Department of Biology, Syracuse University, Syracuse, New York, United States of America.

Metagenomic analyses have advanced our understanding of ecological microbial diversity, but to what extent can metagenomic data be used to predict the metabolic capacity of difficult-to-study organisms and their abiotic environmental interactions? We tackle this question, using a comparative genomic approach, by considering the molecular basis of aerobiosis within archaea. Lipoylation, the covalent attachment of lipoic acid to 2-oxoacid dehydrogenase multienzyme complexes (OADHCs), is essential for metabolism in aerobic bacteria and eukarya. Lipoylation is catalysed either by lipoate protein ligase (LplA), which in archaea is typically encoded by two genes (LplA-N and LplA-C), or by a lipoyl(octanoyl) transferase (LipB or LipM) plus a lipoic acid synthetase (LipA). Does the genomic presence of lipoylation and OADHC genes across archaea from diverse habitats correlate with aerobiosis? First, analyses of 11,826 biotin protein ligase (BPL)-LplA-LipB transferase family members and 147 archaeal genomes identified 85 species with lipoylation capabilities and provided support for multiple ancestral acquisitions of lipoylation pathways during archaeal evolution. Second, with the exception of the Sulfolobales order, the majority of species possessing lipoylation systems exclusively retain LplA, or either LipB or LipM, consistent with archaeal genome streamlining. Third, obligate anaerobic archaea display widespread loss of lipoylation and OADHC genes. Conversely, a high level of correspondence is observed between aerobiosis and the presence of LplA/LipB/LipM, LipA and OADHC E2, consistent with the role of lipoylation in aerobic metabolism. This correspondence between OADHC lipoylation capacity and aerobiosis indicates that genomic pathway profiling in archaea is informative and that well characterized pathways may be predictive in relation to abiotic conditions in difficult-to-study extremophiles. Given the highly variable retention of gene repertoires across the archaea, the extension of comparative genomic pathway profiling to broader metabolic and homeostasis networks should be useful in revealing characteristics from metagenomic datasets related to adaptations to diverse environments.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087063PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904984PMC
December 2014

Chemoreceptor gene loss and acquisition via horizontal gene transfer in Escherichia coli.

J Bacteriol 2013 Aug 7;195(16):3596-602. Epub 2013 Jun 7.

Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA.

Chemotaxis allows bacteria to more efficiently colonize optimal microhabitats within their larger environment. Chemotaxis in Escherichia coli is the best-studied model system, and a large number of E. coli strains have been sequenced. The Escherichia/Shigella genus encompasses a great variety of commensal and pathogenic strains, but the role of chemotaxis in their association with the host remains poorly understood. Here we show that the core chemotaxis genes are lost in many, but not all, nonmotile strains but are well preserved in all motile strains. The genes encoding the Tar, Tsr, and Aer chemoreceptors, which mediate chemotaxis to a broad spectrum of chemical and physical cues, are also nearly uniformly conserved in motile strains. In contrast, the clade of extraintestinal pathogenic E. coli strains apparently underwent an ancestral loss of Trg and Tap chemoreceptors, which sense sugars, dipeptides, and pyrimidines. The broad range of time estimated for the loss of these genes (1 to 3 million years ago) corresponds to the appearance of the genus Homo.
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http://dx.doi.org/10.1128/JB.00421-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754581PMC
August 2013

Azospirillum genomes reveal transition of bacteria from aquatic to terrestrial environments.

PLoS Genet 2011 Dec 22;7(12):e1002430. Epub 2011 Dec 22.

CNRS, UMR 5557, Ecologie Microbienne, Université de Lyon, Villeurbanne, France.

Fossil records indicate that life appeared in marine environments ∼3.5 billion years ago (Gyr) and transitioned to terrestrial ecosystems nearly 2.5 Gyr. Sequence analysis suggests that "hydrobacteria" and "terrabacteria" might have diverged as early as 3 Gyr. Bacteria of the genus Azospirillum are associated with roots of terrestrial plants; however, virtually all their close relatives are aquatic. We obtained genome sequences of two Azospirillum species and analyzed their gene origins. While most Azospirillum house-keeping genes have orthologs in its close aquatic relatives, this lineage has obtained nearly half of its genome from terrestrial organisms. The majority of genes encoding functions critical for association with plants are among horizontally transferred genes. Our results show that transition of some aquatic bacteria to terrestrial habitats occurred much later than the suggested initial divergence of hydro- and terrabacterial clades. The birth of the genus Azospirillum approximately coincided with the emergence of vascular plants on land.
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http://dx.doi.org/10.1371/journal.pgen.1002430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245306PMC
December 2011

FIST: a sensory domain for diverse signal transduction pathways in prokaryotes and ubiquitin signaling in eukaryotes.

Bioinformatics 2007 Oct 12;23(19):2518-21. Epub 2007 Sep 12.

Joint Institute for Computational Sciences, The University of Tennessee - Oak Ridge National Laboratory, Oak Ridge, TN 37831-6173, USA.

Motivation: Sensory domains that are conserved among Bacteria, Archaea and Eucarya are important detectors of common signals detected by living cells. Due to their high sequence divergence, sensory domains are difficult to identify. We systematically look for novel sensory domains using sensitive profile-based searches initiated with regions of signal transduction proteins where no known domains can be identified by current domain models.

Results: Using profile searches followed by multiple sequence alignment, structure prediction and domain architecture analysis, we have identified a novel sensory domain termed FIST, which is present in signal transduction proteins from Bacteria, Archaea and Eucarya. Chromosomal proximity of FIST-encoding genes to those coding for proteins involved in amino acid metabolism and transport suggest that FIST domains bind small ligands, such as amino acids.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067152PMC
http://dx.doi.org/10.1093/bioinformatics/btm384DOI Listing
October 2007
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