scholarly journals Towards functional characterization of archaeal genomic dark matter

2019 ◽  
Vol 47 (1) ◽  
pp. 389-398 ◽  
Author(s):  
Kira S. Makarova ◽  
Yuri I. Wolf ◽  
Eugene V. Koonin

Abstract A substantial fraction of archaeal genes, from ∼30% to as much as 80%, encode ‘hypothetical' proteins or genomic ‘dark matter'. Archaeal genomes typically contain a higher fraction of dark matter compared with bacterial genomes, primarily, because isolation and cultivation of most archaea in the laboratory, and accordingly, experimental characterization of archaeal genes, are difficult. In the present study, we present quantitative characteristics of the archaeal genomic dark matter and discuss comparative genomic approaches for functional prediction for ‘hypothetical' proteins. We propose a list of top priority candidates for experimental characterization with a broad distribution among archaea and those that are characteristic of poorly studied major archaeal groups such as Thaumarchaea, DPANN (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota and Nanohaloarchaeota) and Asgard.

2020 ◽  
Vol 11 ◽  
Author(s):  
Sandra Quilodrán-Vega ◽  
Leonardo Albarracin ◽  
Flavia Mansilla ◽  
Lorena Arce ◽  
Binghui Zhou ◽  
...  

Potential probiotic or immunobiotic effects of lactic acid bacteria (LAB) isolated from the milk of the South American camelid llama (Lama glama) have not been reported in published studies. The aim of the present work was to isolate beneficial LAB from llama milk that can be used as potential probiotics active against bacterial pathogens. LAB strains were isolated from llama milk samples. In vitro functional characterization of the strains was performed by evaluating the resistance against gastrointestinal conditions and inhibition of the pathogen growth. Additionally, the adhesive and immunomodulatory properties of the strains were assessed. The functional studies were complemented with a comparative genomic evaluation and in vivo studies in mice. Ligilactobacillus salivarius TUCO-L2 showed enhanced probiotic/immunobiotic potential compared to that of other tested strains. The TUCO-L2 strain was resistant to pH and high bile salt concentrations and demonstrated antimicrobial activity against Gram-negative intestinal pathogens and adhesion to mucins and epithelial cells. L. salivarius TUCO-L2 modulated the innate immune response triggered by Toll-like receptor (TLR)-4 activation in intestinal epithelial cells. This effect involved differential regulation of the expression of inflammatory cytokines and chemokines mediated by the modulation of the negative regulators of the TLR signaling pathway. Moreover, the TUCO-L2 strain enhanced the resistance of mice to Salmonella infection. This is the first report on the isolation and characterization of a potential probiotic/immunobiotic strain from llama milk. The in vitro, in vivo, and in silico investigation performed in this study reveals several research directions that are needed to characterize the TUCO-L2 strain in detail to position this strain as a probiotic or immunobiotic that can be used against infections in humans or animals, including llama.


2019 ◽  
Vol 36 (12) ◽  
pp. 2805-2812
Author(s):  
Aaron Hardin ◽  
Kimberly A Nevonen ◽  
Walter L Eckalbar ◽  
Lucia Carbone ◽  
Nadav Ahituv

Abstract Mastomys are the most widespread African rodent and carriers of various diseases such as the plague or Lassa virus. In addition, mastomys have rapidly gained a large number of mammary glands. Here, we generated a genome, variome, and transcriptomes for Mastomys coucha. As mastomys diverged at similar times from mouse and rat, we demonstrate their utility as a comparative genomic tool for these commonly used animal models. Furthermore, we identified over 500 mastomys accelerated regions, often residing near important mammary developmental genes or within their exons leading to protein sequence changes. Functional characterization of a noncoding mastomys accelerated region, located in the HoxD locus, showed enhancer activity in mouse developing mammary glands. Combined, our results provide genomic resources for mastomys and highlight their potential both as a comparative genomic tool and for the identification of mammary gland number determining factors.


Botany ◽  
2013 ◽  
Vol 91 (8) ◽  
pp. 495-504 ◽  
Author(s):  
Hao Xu ◽  
Janice E.K. Cooke ◽  
Janusz J. Zwiazek

In mycorrhizal associations, water transport properties of the fungal hyphae may have a profound effect on water transport of the host plant. The importance of aquaporins, water-transporting members of the major intrinsic protein (MIP) family, in facilitating water transport has been widely acknowledged and extensively studied in plants. However, until recently, relatively little was known about the structure, function, and regulation of fungal MIPs. The rapid increase in the number of sequenced fungal genomes, including Laccaria bicolor and other mycorrhizal fungi, has enabled functional and comparative genomic investigations to delineate the role that fungal MIPs play in mycorrhizal-facilitated plant water transport. Phylogenic analysis of 229 fungal MIPs from 88 species revealed that MIPs of mycorrhizal fungal species fall into four clusters delineated by functionally characterized fungal MIPs: the orthodox aquaporins, the aquaglyceroporins, the facultative fungal aquaporins, and the X intrinsic proteins. This comparative genomics analysis, together with in silico structural characterization of predicted MIPs and recently published functional characterization of MIPs from a small number of ectomycorrhizal and arbuscular mycorrhizal species, provide new insight into MIP gene families of mycorrhizal fungi and possible roles for fungal aquaporins in water relations of mycorrhizal plant–fungus symbioses.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Andreas Lange ◽  
Prajal H. Patel ◽  
Brennen Heames ◽  
Adam M. Damry ◽  
Thorsten Saenger ◽  
...  

AbstractComparative genomic studies have repeatedly shown that new protein-coding genes can emerge de novo from noncoding DNA. Still unknown is how and when the structures of encoded de novo proteins emerge and evolve. Combining biochemical, genetic and evolutionary analyses, we elucidate the function and structure of goddard, a gene which appears to have evolved de novo at least 50 million years ago within the Drosophila genus. Previous studies found that goddard is required for male fertility. Here, we show that Goddard protein localizes to elongating sperm axonemes and that in its absence, elongated spermatids fail to undergo individualization. Combining modelling, NMR and circular dichroism (CD) data, we show that Goddard protein contains a large central α-helix, but is otherwise partially disordered. We find similar results for Goddard’s orthologs from divergent fly species and their reconstructed ancestral sequences. Accordingly, Goddard’s structure appears to have been maintained with only minor changes over millions of years.


2021 ◽  
Author(s):  
Andreas Lange ◽  
Prajal H. Patel ◽  
Brennen Heames ◽  
Adam M. Damry ◽  
Thorsten Saenger ◽  
...  

AbstractComparative genomic studies have repeatedly shown that new protein-coding genes can emerge de novo from non-coding DNA. Still unknown is how and when the structures of encoded de novo proteins emerge and evolve. Combining biochemical, genetic and evolutionary analyses, we elucidate the function and structure of goddard, a gene which appears to have evolved de novo at least 50 million years ago within the Drosophila genus.Previous studies found that goddard is required for male fertility. Here, we show that Goddard protein localizes to elongating sperm axonemes and that in its absence, elongated spermatids fail to undergo individualization. Combining modelling, NMR and CD data, we show that Goddard protein contains a large central α-helix, but is otherwise partially disordered. We find similar results for Goddard’s orthologs from divergent fly species and their reconstructed ancestral sequences. Accordingly, Goddard’s structure appears to have been maintained with only minor changes over millions of years.


2019 ◽  
Vol 21 (4) ◽  
pp. 1391-1396 ◽  
Author(s):  
Meik Kunz ◽  
Beat Wolf ◽  
Maximilian Fuchs ◽  
Jan Christoph ◽  
Ke Xiao ◽  
...  

Abstract Long non-coding RNAs (lncRNAs) are of fundamental biological importance; however, their functional role is often unclear or loosely defined as experimental characterization is challenging and bioinformatic methods are limited. We developed a novel integrated method protocol for the annotation and detailed functional characterization of lncRNAs within the genome. It combines annotation, normalization and gene expression with sequence-structure conservation, functional interactome and promoter analysis. Our protocol allows an analysis based on the tissue and biological context, and is powerful in functional characterization of experimental and clinical RNA-Seq datasets including existing lncRNAs. This is demonstrated on the uncharacterized lncRNA GATA6-AS1 in dilated cardiomyopathy.


2020 ◽  
Author(s):  
Xi Lin ◽  
Junwan Lu ◽  
Changrui Qian ◽  
Hailong Lin ◽  
Qiaoling Li ◽  
...  

Abstract BackgroundAeromonas hydrophila is a zoonotic and human opportunistic pathogen. Increasing antibiotic resistance profiles have been discovered in both clinical and environmental A. hydrophila isolates in recent years. However, there are still very few in-depth studies regarding the role of plasmids in antibiotic resistance of A. hydrophila. Hence, we investigate the molecular characterization and functional characterization of a multidrug resistant plasmid which encoding a novel NDM variant, AFM-1, in clinical A. hydrophila SS332.MethodsThe minimum inhibitory concentrations (MICs) of 24 antibiotics for A. hydrophila SS332 were measured by the agar dilution method. The genome of A. hydrophila SS332 was sequenced with Pacific and Illumina platforms. Six plasmid-borne antimicrobial resistance genes were chosen for cloning, including blaAFM-1, blaOXA-1, msr(E), mph(E), aac(6')-Ib10, and aph(3')-Ia. Phylogenetic analysis, amino acid sequence alignment, and comparative genomic analysis were performed to elucidate the active site requirements and genetic context of blaAFM-1 gene.ResultsA. hydrophila SS332 showed high levels of resistance to 15 antibiotics, especially those with MIC levels up to or higher than 1024 μg/mL, including ampicillin, cefazolin, ceftriaxone, aztreonam, spectinomycin, roxithromycin. Six plasmid-borne resistance genes were verified to be functional in E. coli DH5α. The blaAFM-1 gene, a novel blaNDM variant, encodes a subclass B1 metallo-β-lactamase AFM-1 which shares 86% amino acid identity with NDM-1. AFM-1 showed resistance to penicillins, cephalosporins and carbapenems. Besides, blaAFM-1 gene was associated with three different novel ISCR19-like elements, designated ISCR19-1, ISCR19-2 and ∆ISCR19-3, which may be involved in the acquisition and mobilization of blaAFM-1 gene. ConclusionsOur investigation showed that plasmid-borne resistance genes played a major role in the resistance profiles of A. hydrophila SS332. A novel blaNDM variant, blaAFM-1, was verified to be functional and disseminated among different bacteria species mediated by novel ISCR19-like elements. The fact indicated that the risk of spread of novel resistance genes and novel ISCR elements.


Sign in / Sign up

Export Citation Format

Share Document