Metabolic Gene Clusters in Eukaryotes

2018 ◽  
Vol 52 (1) ◽  
pp. 159-183 ◽  
Author(s):  
Hans-Wilhelm Nützmann ◽  
Claudio Scazzocchio ◽  
Anne Osbourn

In bacteria, more than half of the genes in the genome are organized in operons. In contrast, in eukaryotes, functionally related genes are usually dispersed across the genome. There are, however, numerous examples of functional clusters of nonhomologous genes for metabolic pathways in fungi and plants. Despite superficial similarities with operons (physical clustering, coordinate regulation), these clusters have not usually originated by horizontal gene transfer from bacteria, and (unlike operons) the genes are typically transcribed separately rather than as a single polycistronic message. This clustering phenomenon raises intriguing questions about the origins of clustered metabolic pathways in eukaryotes and the significance of clustering for pathway function. Here we review metabolic gene clusters from fungi and plants, highlight commonalities and differences, and consider how these clusters form and are regulated. We also identify opportunities for future research in the areas of large-scale genomics, synthetic biology, and experimental evolution.

2021 ◽  
Author(s):  
Jinjin Tao ◽  
Sishuo Wang ◽  
Tianhua Liao ◽  
Haiwei Luo

SummaryThe alphaproteobacterial genus Bradyrhizobium has been best known as N2-fixing members that nodulate legumes, supported by the nif and nod gene clusters. Recent environmental surveys show that Bradyrhizobium represents one of the most abundant free-living bacterial lineages in the world’s soils. However, our understanding of Bradyrhizobium comes largely from symbiotic members, biasing the current knowledge of their ecology and evolution. Here, we report the genomes of 88 Bradyrhizobium strains derived from diverse soil samples, including both nif-carrying and non-nif-carrying free-living (nod free) members. Phylogenomic analyses of these and 252 publicly available Bradyrhizobium genomes indicate that nif-carrying free-living members independently evolved from symbiotic ancestors (carrying both nif and nod) multiple times. Intriguingly, the nif phylogeny shows that all nif-carrying free-living members comprise a cluster which branches off earlier than most symbiotic lineages. These results indicate that horizontal gene transfer (HGT) promotes nif expansion among the free-living Bradyrhizobium and that the free-living nif cluster represents a more ancestral version compared to that in symbiotic lineages. Further evidence for this rampant HGT is that the nif in free-living members consistently co-locate with several important genes involved in coping with oxygen tension which are missing from symbiotic members, and that while in free-living Bradyrhizobium nif and the co-locating genes show a highly conserved gene order, they each have distinct genomic context. Given the dominance of Bradyrhizobium in world’s soils, our findings have implications for global nitrogen cycles and agricultural research.


2020 ◽  
Vol 10 (9) ◽  
pp. 3417-3433
Author(s):  
Javier F Tabima ◽  
Ian A Trautman ◽  
Ying Chang ◽  
Yan Wang ◽  
Stephen Mondo ◽  
...  

Abstract Research into secondary metabolism (SM) production by fungi has resulted in the discovery of diverse, biologically active compounds with significant medicinal applications. The fungi rich in SM production are taxonomically concentrated in the subkingdom Dikarya, which comprises the phyla Ascomycota and Basidiomycota. Here, we explore the potential for SM production in Mucoromycota and Zoopagomycota, two phyla of nonflagellated fungi that are not members of Dikarya, by predicting and identifying core genes and gene clusters involved in SM. The majority of non-Dikarya have few genes and gene clusters involved in SM production except for the amphibian gut symbionts in the genus Basidiobolus. Basidiobolus genomes exhibit an enrichment of SM genes involved in siderophore, surfactin-like, and terpene cyclase production, all these with evidence of constitutive gene expression. Gene expression and chemical assays also confirm that Basidiobolus has significant siderophore activity. The expansion of SMs in Basidiobolus are partially due to horizontal gene transfer from bacteria, likely as a consequence of its ecology as an amphibian gut endosymbiont.


Genes ◽  
2019 ◽  
Vol 10 (8) ◽  
pp. 569 ◽  
Author(s):  
Phale ◽  
Shah ◽  
Malhotra

In the biosphere, the largest biological laboratory, increased anthropogenic activities have led microbes to evolve and adapt to the changes occurring in the environment. Compounds, specifically xenobiotics, released due to such activities persist in nature and undergo bio-magnification in the food web. Some of these compounds act as potent endocrine disrupters, mutagens or carcinogens, and therefore their removal from the environment is essential. Due to their persistence, microbial communities have evolved to metabolize them partially or completely. Diverse biochemical pathways have evolved or been assembled by exchange of genetic material (horizontal gene transfer) through various mobile genetic elements like conjugative and non-conjugative plasmids, transposons, phages and prophages, genomic islands and integrative conjugative elements. These elements provide an unlimited opportunity for genetic material to be exchanged across various genera, thus accelerating the evolution of a new xenobiotic degrading phenotype. In this article, we illustrate examples of the assembly of metabolic pathways involved in the degradation of naphthalene and its derivative, Carbaryl, which are speculated to have evolved or adapted through the above-mentioned processes.


2008 ◽  
Vol 9 (2) ◽  
pp. 115-126 ◽  
Author(s):  
Patrick Boerlin ◽  
Richard J. Reid-Smith

AbstractNew concepts have emerged in the past few years that help us to better understand the emergence and spread of antimicrobial resistance (AMR). These include, among others, the discovery of the mutator state and the concept of mutant selection window for resistances emerging primarily through mutations in existing genes. Our understanding of horizontal gene transfer has also evolved significantly in the past few years, and important new mechanisms of AMR transfer have been discovered, including, among others, integrative conjugative elements and ISCR(insertionsequences withcommonregions) elements. Simultaneously, large-scale studies have helped us to start comprehending the immense and yet untapped reservoir of both AMR genes and mobile genetic elements present in the environment. Finally, new PCR- and DNA sequencing-based techniques are being developed that will allow us to better understand the epidemiology of classical vectors of AMR genes, such as plasmids, and to monitor them in a more global and systematic way.


2013 ◽  
Author(s):  
Kevin Dougherty ◽  
Brian A Smith ◽  
Autum F Moore ◽  
Shannon Maitland ◽  
Chris Fanger ◽  
...  

Horizontal gene transfer often leads to phenotypic changes within recipient organisms independent of any immediate evolutionary benefits. While secondary phenotypic effects of horizontal transfer (i.e. changes in growth rates) have been demonstrated and studied across a variety of systems using relatively small plasmid and phage, little is known about how size of the acquired region affects the magnitude or number of such costs. Here we describe an amazing breadth of phenotypic changes which occur after a large-scale horizontal transfer event (~1Mb megaplasmid) within Pseudomonas stutzeri including sensitization to various stresses as well as changes in bacterial behavior. These results highlight the power of horizontal transfer to shift pleiotropic relationships and cellular networks within bacterial genomes. They also provide an important context for how secondary effects of transfer can bias evolutionary trajectories and interactions between species. Lastly, these results and system provide a foundation to investigate evolutionary consequences in real time as newly acquired regions are ameliorated and integrated into new genomic contexts.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Suwen Zhao ◽  
Ayano Sakai ◽  
Xinshuai Zhang ◽  
Matthew W Vetting ◽  
Ritesh Kumar ◽  
...  

Metabolic pathways in eubacteria and archaea often are encoded by operons and/or gene clusters (genome neighborhoods) that provide important clues for assignment of both enzyme functions and metabolic pathways. We describe a bioinformatic approach (genome neighborhood network; GNN) that enables large scale prediction of the in vitro enzymatic activities and in vivo physiological functions (metabolic pathways) of uncharacterized enzymes in protein families. We demonstrate the utility of the GNN approach by predicting in vitro activities and in vivo functions in the proline racemase superfamily (PRS; InterPro IPR008794). The predictions were verified by measuring in vitro activities for 51 proteins in 12 families in the PRS that represent ~85% of the sequences; in vitro activities of pathway enzymes, carbon/nitrogen source phenotypes, and/or transcriptomic studies confirmed the predicted pathways. The synergistic use of sequence similarity networks3 and GNNs will facilitate the discovery of the components of novel, uncharacterized metabolic pathways in sequenced genomes.


2021 ◽  
Author(s):  
Apurva Narechania ◽  
Rob DeSalle ◽  
Barun Mathema ◽  
Barry N Kreiswirth ◽  
Paul J Planet

Most microbes have the capacity to acquire genetic material from their environment. Recombination of foreign DNA yields genomes that are, at least in part, incongruent with the vertical history of their species. Dominant approaches for detecting such horizontal gene transfer (HGT) and recombination are phylogenetic, requiring a painstaking series of analyses including sequence-based clustering, alignment, and phylogenetic tree reconstruction. Given the breakneck pace of genome sequencing, these traditional pan-genomic methods do not scale. Here we propose an alignment-free and tree-free technique based on the sequential information bottleneck (SIB), an optimization procedure designed to extract some portion of relevant information from one random variable conditioned on another. In our case, this joint probability distribution tabulates occurrence counts of k-mers with respect to their genomes of origin (the relevance information) with the expectation that HGT and recombination will create a strong signal that distinguishes certain sets of co-occuring k-mers. The technique is conceptualized as a rate-distortion problem. We measure distortion in the relevance information as k-mers are compressed into clusters based on their co-occurrence in the source genomes. This approach is similar to topic mining in the Natural Language Processing (NLP) literature. The result is model-free, unsupervised compression of k-mers into genomic topics that trace tracts of shared genome sequence whether vertically or horizontally acquired. We examine the performance of SIB on simulated data and on the known large-scale recombination event that formed the Staphylococcus aureus ST239 clade. We use this technique to detect recombined regions and recover the vertically inherited core genome with a fraction of the computing power required of current phylogenetic methods.


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