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Featured researches published by Brendan Epstein.


PLOS ONE | 2013

Candidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in Medicago truncatula.

John Stanton-Geddes; Timothy Paape; Brendan Epstein; Roman Briskine; Jeremy B. Yoder; Joann Mudge; Arvind K. Bharti; Andrew D. Farmer; Peng Zhou; Roxanne Denny; Gregory D. May; Stephanie Erlandson; Mohammed Yakub; Masayuki Sugawara; Michael J. Sadowsky; Nevin D. Young; Peter Tiffin

Genome-wide association study (GWAS) has revolutionized the search for the genetic basis of complex traits. To date, GWAS have generally relied on relatively sparse sampling of nucleotide diversity, which is likely to bias results by preferentially sampling high-frequency SNPs not in complete linkage disequilibrium (LD) with causative SNPs. To avoid these limitations we conducted GWAS with >6 million SNPs identified by sequencing the genomes of 226 accessions of the model legume Medicago truncatula. We used these data to identify candidate genes and the genetic architecture underlying phenotypic variation in plant height, trichome density, flowering time, and nodulation. The characteristics of candidate SNPs differed among traits, with candidates for flowering time and trichome density in distinct clusters of high linkage disequilibrium (LD) and the minor allele frequencies (MAF) of candidates underlying variation in flowering time and height significantly greater than MAF of candidates underlying variation in other traits. Candidate SNPs tagged several characterized genes including nodulation related genes SERK2, MtnodGRP3, MtMMPL1, NFP, CaML3, MtnodGRP3A and flowering time gene MtFD as well as uncharacterized genes that become candidates for further molecular characterization. By comparing sequence-based candidates to candidates identified by in silico 250K SNP arrays, we provide an empirical example of how reliance on even high-density reduced representation genomic makers can bias GWAS results. Depending on the trait, only 30–70% of the top 20 in silico array candidates were within 1 kb of sequence-based candidates. Moreover, the sequence-based candidates tagged by array candidates were heavily biased towards common variants; these comparisons underscore the need for caution when interpreting results from GWAS conducted with sparsely covered genomes.


Genome Biology | 2013

Comparative genomics of the core and accessory genomes of 48 Sinorhizobium strains comprising five genospecies

Masayuki Sugawara; Brendan Epstein; Brian D. Badgley; Tatsuya Unno; Lei Xu; Jennifer Reese; Prasad Gyaneshwar; Roxanne Denny; Joann Mudge; Arvind K. Bharti; Andrew D. Farmer; Gregory D. May; Jimmy E. Woodward; Claudine Médigue; David Vallenet; Aurélie Lajus; Zoé Rouy; Betsy M. Martinez-Vaz; Peter Tiffin; Nevin D. Young; Michael J. Sadowsky

BackgroundThe sinorhizobia are amongst the most well studied members of nitrogen-fixing root nodule bacteria and contribute substantial amounts of fixed nitrogen to the biosphere. While the alfalfa symbiont Sinorhizobium meliloti RM 1021 was one of the first rhizobial strains to be completely sequenced, little information is available about the genomes of this large and diverse species group.ResultsHere we report the draft assembly and annotation of 48 strains of Sinorhizobium comprising five genospecies. While S. meliloti and S. medicae are taxonomically related, they displayed different nodulation patterns on diverse Medicago host plants, and have differences in gene content, including those involved in conjugation and organic sulfur utilization. Genes involved in Nod factor and polysaccharide biosynthesis, denitrification and type III, IV, and VI secretion systems also vary within and between species. Symbiotic phenotyping and mutational analyses indicated that some type IV secretion genes are symbiosis-related and involved in nitrogen fixation efficiency. Moreover, there is a correlation between the presence of type IV secretion systems, heme biosynthesis and microaerobic denitrification genes, and symbiotic efficiency.ConclusionsOur results suggest that each Sinorhizobium strain uses a slightly different strategy to obtain maximum compatibility with a host plant. This large genome data set provides useful information to better understand the functional features of five Sinorhizobium species, especially compatibility in legume-Sinorhizobium interactions. The diversity of genes present in the accessory genomes of members of this genus indicates that each bacterium has adopted slightly different strategies to interact with diverse plant genera and soil environments.


PLOS Genetics | 2012

Population Genomics of the Facultatively Mutualistic Bacteria Sinorhizobium meliloti and S. medicae

Brendan Epstein; Antoine Branca; Joann Mudge; Arvind K. Bharti; Roman Briskine; Andrew D. Farmer; Masayuki Sugawara; Nevin D. Young; Michael J. Sadowsky; Peter Tiffin

The symbiosis between rhizobial bacteria and legume plants has served as a model for investigating the genetics of nitrogen fixation and the evolution of facultative mutualism. We used deep sequence coverage (>100×) to characterize genomic diversity at the nucleotide level among 12 Sinorhizobium medicae and 32 S. meliloti strains. Although these species are closely related and share host plants, based on the ratio of shared polymorphisms to fixed differences we found that horizontal gene transfer (HGT) between these species was confined almost exclusively to plasmid genes. Three multi-genic regions that show the strongest evidence of HGT harbor genes directly involved in establishing or maintaining the mutualism with host plants. In both species, nucleotide diversity is 1.5–2.5 times greater on the plasmids than chromosomes. Interestingly, nucleotide diversity in S. meliloti but not S. medicae is highly structured along the chromosome – with mean diversity (θπ) on one half of the chromosome five times greater than mean diversity on the other half. Based on the ratio of plasmid to chromosome diversity, this appears to be due to severely reduced diversity on the chromosome half with less diversity, which is consistent with extensive hitchhiking along with a selective sweep. Frequency-spectrum based tests identified 82 genes with a signature of adaptive evolution in one species or another but none of the genes were identified in both species. Based upon available functional information, several genes identified as targets of selection are likely to alter the symbiosis with the host plant, making them attractive targets for further functional characterization.


Evolution | 2012

Do trade-offs have explanatory power for the evolution of organismal interactions?

Mark K. Asplen; Emily Bruns; Aaron S. David; R. Ford Denison; Brendan Epstein; Matthew C. Kaiser; Joe M. Kaser; Christelle Lacroix; Emily K. Mohl; Gina Quiram; Kristina K Prescott; John Stanton-Geddes; John B. Vincent; Peter D. Wragg; Georgiana May

The concept of a trade‐off has long played a prominent role in understanding the evolution of organismal interactions such as mutualism, parasitism, and competition. Given the complexity inherent to interactions between different evolutionary entities, ecological factors may especially limit the power of trade‐off models to predict evolutionary change. Here, we use four case studies to examine the importance of ecological context for the study of trade‐offs in organismal interactions: (1) resource‐based mutualisms, (2) parasite transmission and virulence, (3) plant biological invasions, and (4) host range evolution in parasites and parasitoids. In the first two case studies, mechanistic trade‐off models have long provided a strong theoretical framework but face the challenge of testing assumptions under ecologically realistic conditions. Work under the second two case studies often has a strong ecological grounding, but faces challenges in identifying or quantifying the underlying genetic mechanism of the trade‐off. Attention is given to recent studies that have bridged the gap between evolutionary mechanism and ecological realism. Finally, we explore the distinction between ecological factors that mask the underlying evolutionary trade‐offs, and factors that actually change the trade‐off relationship between fitness‐related traits important to organismal interactions.


Genome Biology and Evolution | 2014

Selection on Horizontally Transferred and Duplicated Genes in Sinorhizobium (Ensifer), the Root-Nodule Symbionts of Medicago

Brendan Epstein; Michael J. Sadowsky; Peter Tiffin

Structural variation, including variation in gene copy number and presence or absence of genes, is a widespread and important source of genomic variation. We used whole-genome DNA sequences from 48 strains of Sinorhizobium (recently renamed Ensifer), including 20 strains of Sinorhizobium meliloti and 12 strains of S. medicae that were the focus of the analyses, to study the fitness effects of new structural variants created by duplication and horizontal gene transfer. We find that derived duplicated and horizontally transferred (HT) genes segregate at lower frequency than synonymous and nonsynonymous nucleotide variants in S. meliloti and S. medicae. Furthermore, the relative frequencies of different types of variants are more similar in S. medicae than in S. meliloti, the species with the larger effective population size. These results are consistent with the hypothesis that most duplications and HT genes have deleterious effects. Diversity of duplications, as measured by segregating duplicated genes per gene, is greater than nucleotide diversity, consistent with a high rate of duplication. Our results suggest that the vast majority of structural variants found among closely related bacterial strains are short-lived and unlikely to be involved in species-wide adaptation.


Conservation Genetics | 2017

Conservation implications of limited genetic diversity and population structure in Tasmanian devils (Sarcophilus harrisii)

Sarah A. Hendricks; Brendan Epstein; Barbara Schönfeld; Cody Wiench; Rodrigo Hamede; Menna E. Jones; Andrew Storfer; Paul A. Hohenlohe

Tasmanian devils face a combination of threats to persistence, including devil facial tumor disease (DFTD), an epidemic transmissible cancer. We used RAD sequencing to investigate genome-wide patterns of genetic diversity and geographic population structure. Consistent with previous results, we found very low genetic diversity in the species as a whole, and we detected two broad genetic clusters occupying the northwestern portion of the range, and the central and eastern portions. However, these two groups overlap across a broad geographic area, and differentiation between them is modest (


G3: Genes, Genomes, Genetics | 2016

Comparative Genomics of an Emerging Amphibian Virus

Brendan Epstein; Andrew Storfer


PLOS ONE | 2017

Using NextRAD sequencing to infer movement of herbivores among host plants

Zhen Fu; Brendan Epstein; Joanna L. Kelley; Qi Zheng; Alan O. Bergland; Carmen I. Castillo Carrillo; Andrew S. Jensen; Jennifer Dahan; Alexander V. Karasev; William E. Snyder

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Proceedings of the National Academy of Sciences of the United States of America | 2018

Select and resequence reveals relative fitness of bacteria in symbiotic and free-living environments

Liana T. Burghardt; Brendan Epstein; Joseph Guhlin; Matthew S. Nelson; Margaret R. Taylor; Nevin D. Young; Michael J. Sadowsky; Peter Tiffin


Molecular Ecology | 2018

Large-effect loci affect survival in Tasmanian devils (Sarcophilus harrisii) infected with a transmissible cancer

Mark J. Margres; Menna E. Jones; Brendan Epstein; Douglas H. Kerlin; Sébastien Comte; Samantha Fox; Alexandra K. Fraik; Sarah A. Hendricks; Stewart Huxtable; Shelly Lachish; Billie Lazenby; Sean O'Rourke; Amanda Stahlke; Cody Wiench; Rodrigo Hamede; Barbara Schönfeld; Hamish McCallum; Michael R. Miller; Paul A. Hohenlohe; Andrew Storfer

FST = 0.1081). Our results refine the geographic extent of the zone of mixed ancestry and substructure within it, potentially informing management of genetic variation that existed in pre-diseased populations of the species. DFTD has spread across both genetic clusters, but recent evidence points to a genomic response to selection imposed by DFTD. Any allelic variation for resistance to DFTD may be able to spread across the devil population under selection by DFTD, and/or be present as standing variation in both genetic regions.

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Peter Tiffin

University of Minnesota

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Andrew Storfer

Washington State University

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Andrew D. Farmer

National Center for Genome Resources

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Arvind K. Bharti

National Center for Genome Resources

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