Systemix Institute

Redmond, WA, United States

Systemix Institute

Redmond, WA, United States
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Gallant J.R.,Michigan State University | Traeger L.L.,University of Wisconsin - Madison | Volkening J.D.,University of Wisconsin - Madison | Moffett H.,Dana-Farber Cancer Institute | And 19 more authors.
Science | Year: 2014

Little is known about the genetic basis of convergent traits that originate repeatedly over broad taxonomic scales. The myogenic electric organ has evolved six times in fishes to produce electric fields used in communication, navigation, predation, or defense.We have examined the genomic basis of the convergent anatomical and physiological origins of these organs by assembling the genome of the electric eel (Electrophorus electricus) and sequencing electric organ and skeletal muscle transcriptomes from three lineages that have independently evolved electric organs. Our results indicate that, despite millions of years of evolution and large differences in the morphology of electric organ cells, independent lineages have leveraged similar transcription factors and developmental and cellular pathways in the evolution of electric organs.

PubMed | University of Groningen, Systemix Institute, Goddard College and University of Detroit Mercy
Type: Journal Article | Journal: PloS one | Year: 2016

We critically re-examine Fredrickson et al.s renewed claims concerning the differential relationship between hedonic and eudaimonic forms of well-being and gene expression, namely that people who experience a preponderance of eudaimonic well-being have gene expression profiles that are associated with more favorable health outcomes. By means of an extensive reanalysis of their data, we identify several discrepancies between what these authors claimed and what their data support; we further show that their different analysis models produce mutually contradictory results. We then show how Fredrickson et al.s most recent article on this topic not only fails to adequately address our previously published concerns about their earlier related work, but also introduces significant further problems, including inconsistency in their hypotheses. Additionally, we demonstrate that regardless of which statistical model is used to analyze their data, Fredrickson et al.s method can be highly sensitive to the inclusion (or exclusion) of data from a single subject. We reiterate our previous conclusions, namely that there is no evidence that Fredrickson et al. have established a reliable empirical distinction between their two delineated forms of well-being, nor that eudaimonic well-being provides any overall health benefits over hedonic well-being.

Guth R.,New Mexico State University | Chaidez A.,New Mexico State University | Samanta M.P.,Systemix Institute | Unguez G.A.,New Mexico State University
Physiological Genomics | Year: 2016

Skeletal muscle is distinguished from other tissues on the basis of its shape, biochemistry, and physiological function. Based on mammalian studies, fiber size, fiber types, and gene expression profiles are regulated, in part, by the electrical activity exerted by the nervous system. To address whether similar adaptations to changes in electrical activity in skeletal muscle occur in teleosts, we studied these phenotypic properties of ventral muscle in the electric fish Sternopygus macrurus following 2 and 5 days of electrical inactivation by spinal transection. Our data show that morphological and biochemical properties of skeletal muscle remained largely unchanged after these treatments. Specifically, the distribution of type I and type II muscle fibers and the crosssectional areas of these fiber types observed in control fish remained unaltered after each spinal transection survival period. This response to electrical inactivation was generally reflected at the transcript level in real-time PCR and RNA-seq data by showing little effect on the transcript levels of genes associated with muscle fiber type differentiation and plasticity, the sarcomere complex, and pathways implicated in the regulation of muscle fiber size. Data from this first study characterizing the acute influence of neural activity on muscle mass and sarcomere gene expression in a teleost are discussed in the context of comparative studies in mammalian model systems and vertebrate species from different lineages. © 2016, American Physiological Society. All rights reserved.

PubMed | Systemix Institute and New Mexico State University
Type: | Journal: PeerJ | Year: 2016

In most electric fish species, the electric organ (EO) derives from striated muscle cells that suppress many muscle properties. In the gymnotiform Sternopygus macrurus, mature electrocytes, the current-producing cells of the EO, do not contain sarcomeres, yet they continue to make some cytoskeletal and sarcomeric proteins and the muscle transcription factors (MTFs) that induce their expression. In order to more comprehensively examine the transcriptional regulation of genes associated with the formation and maintenance of the contractile sarcomere complex, results from expression analysis using qRT-PCR were informed by deep RNA sequencing of transcriptomes and miRNA compositions of muscle and EO tissues from adult S. macrurus. Our data show that: (1) components associated with the homeostasis of the sarcomere and sarcomere-sarcolemma linkage were transcribed in EO at levels similar to those in muscle; (2) MTF families associated with activation of the skeletal muscle program were not differentially expressed between these tissues; and (3) a set of microRNAs that are implicated in regulation of the muscle phenotype are enriched in EO. These data support the development of a unique and highly specialized non-contractile electrogenic cell that emerges from a striated phenotype and further differentiates with little modification in its transcript composition. This comprehensive analysis of parallel mRNA and miRNA profiles is not only a foundation for functional studies aimed at identifying mechanisms underlying the transcription-independent myogenic program in S. macrurus EO, but also has important implications to many vertebrate cell types that independently activate or suppress specific features of the skeletal muscle program.

PubMed | Systemix Institute and New Mexico State University
Type: | Journal: Journal of physiology, Paris | Year: 2016

Electrical activity is an important regulator of cellular function and gene expression in electrically excitable cell types. In the weakly electric teleost fish Sternopygus macrurus, electrocytes, i.e., the current-producing cells of the electric organ, derive from a striated muscle lineage. Mature electrocytes are larger than muscle fibers, do not contain sarcomeres, and are driven continuously at frequencies higher than those exerted on muscle cells. Previous work showed that the removal of electrical activity by spinal cord transection (ST) for two and five weeks led to an upregulation of some sarcomeric proteins and a decrease in electrocyte size. To test whether changes in gene transcription preceded these phenotypic changes, we determined the sensitivity of electrocyte gene expression to electrical inactivity periods of two and five days after ST. Whole tissue gene expression profiles using deep RNA sequencing showed minimal alterations in the levels of myogenic transcription factor and sarcomeric transcripts after either ST period. Moreover, while analysis of differentially expressed genes showed a transient upregulation of genes associated with proteolytic mechanisms at two days and an increase in mRNA levels of cytoskeletal genes at five days after electrical silencing, electrocyte size was not affected. Electrical inactivity also resulted in the downregulation of genes that were classified into enriched clusters associated with functions of axon migration and synapse structure. Overall, these data demonstrate that unlike tissues in the myogenic lineage in other vertebrate species, regulation of gene transcription and cell size in the muscle-like electrocytes of S. macrurus is highly insensitive to short-term electrical inactivity. Moreover, together with data obtained from control and long-term ST studies, the present data suggest that neural input might influence post-transcriptional processes to affect the mature electrocyte phenotype.

Ozdemir A.,California Institute of Technology | Fisher-Aylor K.I.,California Institute of Technology | Pepke S.,California Institute of Technology | Samanta M.,Systemix Institute | And 6 more authors.
Genome Research | Year: 2011

Cis-regulatory modules (CRMs) function by binding sequence specific transcription factors, but the relationship between in vivo physical binding and the regulatory capacity of factor-bound DNA elements remains uncertain. We investigate this relationship for the well-studied Twist factor in Drosophila melanogaster embryos by analyzing genome-wide factor occupancy and testing the functional significance of Twist occupied regions and motifs within regions. Twist ChIP-seq data efficiently identified previously studied Twist-dependent CRMs and robustly predicted new CRM activity in transgenesis, with newly identified Twist-occupied regions supporting diverse spatiotemporal patterns (>74% positive, n = 31). Some, but not all, candidate CRMs require Twist for proper expression in the embryo. The Twist motifs most favored in genome ChIP data (in vivo) differed from those most favored by Systematic Evolution of Ligands by EXponential enrichment (SELEX) (in vitro). Furthermore, the majority of ChIP-seq signals could be parsimoniously explained by a CABVTG motif located within 50 bp of the ChIP summit and, of these, CACATG was most prevalent. Mutagenesis experiments demonstrated that different Twist E-box motif types are not fully interchangeable, suggesting that the ChIP-derived consensus (CABVTG) includes sites having distinct regulatory outputs. Further analysis of position, frequency of occurrence, and sequence conservation revealed significant enrichment and conservation of CABVTG E-box motifs near Twist ChIP-seq signal summits, preferential conservation of ±150 bp surrounding Twist occupied summits, and enrichment of GA- and CA-repeat sequences near Twist occupied summits. Our results show that high resolution in vivo occupancy data can be used to drive efficient discovery and dissection of global and local cis-regulatory logic. © 2011 by Cold Spring Harbor Laboratory Press.

PubMed | University of Washington, Systemix Institute, Washington State University and Humboldt State University
Type: Journal Article | Journal: PloS one | Year: 2015

Acoustic communication is essential for the reproductive success of the plainfin midshipman fish (Porichthys notatus). During the breeding season, type I males use acoustic cues to advertise nest location to potential mates, creating an audible signal that attracts reproductive females. Type II (sneaker) males also likely use this social acoustic signal to find breeding pairs from which to steal fertilizations. Estrogen-induced changes in the auditory system of breeding females are thought to enhance neural encoding of the advertisement call, and recent anatomical data suggest the saccule (the main auditory end organ) as one possible target for this seasonal modulation. Here we describe saccular transcriptomes from all three sexual phenotypes (females, type I and II males) collected during the breeding season as a first step in understanding the mechanisms underlying sexual phenotype-specific and seasonal differences in auditory function. We used RNA-Seq on the Ion Torrent platform to create a combined transcriptome dataset containing over 79,000 assembled transcripts representing almost 9,000 unique annotated genes. These identified genes include several with known inner ear function and multiple steroid hormone receptors. Transcripts most closely matched to published genomes of nile tilapia and large yellow croaker, inconsistent with the phylogenetic relationship between these species but consistent with the importance of acoustic communication in their life-history strategies. We then compared the RNA-Seq results from the saccules of reproductive females with a separate transcriptome from the non-reproductive female phenotype and found over 700 differentially expressed transcripts, including members of the Wnt and Notch signaling pathways that mediate cell proliferation and hair cell addition in the inner ear. These data constitute a valuable resource for furthering our understanding of the molecular basis for peripheral auditory function as well as a range of future midshipman and cross-species comparative studies of the auditory periphery.

PubMed | Systemix Institute and Ohio State University
Type: Journal Article | Journal: Biomolecules | Year: 2016

RNase P, a ribozyme-based ribonucleoprotein (RNP) complex that catalyzes tRNA 5-maturation, is ubiquitous in all domains of life, but the evolution of its protein components (RNase P proteins, RPPs) is not well understood. Archaeal RPPs may provide clues on how the complex evolved from an ancient ribozyme to an RNP with multiple archaeal and eukaryotic (homologous) RPPs, which are unrelated to the single bacterial RPP. Here, we analyzed the sequence and structure of archaeal RPPs from over 600 available genomes. All five RPPs are found in eight archaeal phyla, suggesting that these RPPs arose early in archaeal evolutionary history. The putative ancestral genomic loci of archaeal RPPs include genes encoding several members of ribosome, exosome, and proteasome complexes, which may indicate coevolution/coordinate regulation of RNase P with other core cellular machineries. Despite being ancient, RPPs generally lack sequence conservation compared to other universal proteins. By analyzing the relative frequency of residues at every position in the context of the high-resolution structures of each of the RPPs (either alone or as functional binary complexes), we suggest residues for mutational analysis that may help uncover structure-function relationships in RPPs.

Hedgecock D.,University of Southern California | Shin G.,University of Southern California | Gracey A.Y.,University of Southern California | van den Berg D.,University of Southern California | Samanta M.P.,Systemix Institute
G3: Genes, Genomes, Genetics | Year: 2015

The Pacific oyster Crassostrea gigas, a widely cultivated marine bivalve mollusc, is becoming a genetically and genomically enabled model for highly fecund marine metazoans with complex life-histories. A genome sequence is available for the Pacific oyster, as are first-generation, low-density, linkage and gene-centromere maps mostly constructed from microsatellite DNA makers. Here, higher density, secondgeneration, linkage maps are constructed from more than 1100 coding (exonic) single-nucleotide polymorphisms (SNPs), as well as 66 previously mapped microsatellite DNA markers, all typed in five families of Pacific oysters (nearly 172,000 genotypes). The map comprises 10 linkage groups, as expected, has an average total length of 588 cM, an average marker-spacing of 1.0 cM, and covers 86% of a genome estimated to be 616 cM. All but seven of the mapped SNPs map to 618 genome scaffolds; 260 scaffolds contain two or more mapped SNPs, but for 100 of these scaffolds (38.5%), the contained SNPs map to different linkage groups, suggesting widespread errors in scaffold assemblies. The 100 misassembled scaffolds are significantly longer than those that map to a single linkage group. On the genetic maps, marker orders and intermarker distances vary across families and mapping methods, owing to an abundance of markers segregating from only one parent, to widespread distortions of segregation ratios caused by early mortality, as previously observed for oysters, and to genotyping errors. Maps made from framework markers provide stronger support for marker orders and reasonable map lengths and are used to produce a consensus high-density linkage map containing 656 markers. © 2015 Hedgecock et al.

Richardson C.R.,Texas Tech University | Luo Q.-J.,Texas Tech University | Gontcharova V.,Texas Tech University | Jiang Y.-W.,Texas Tech University | And 3 more authors.
PLoS ONE | Year: 2010

Background: MicroRNAs (miRNAs) and trans-acting small-interfering RNAs (tasi-RNAs) are small (20-22 nt long) RNAs (smRNAs) generated from hairpin secondary structures or antisense transcripts, respectively, that regulate gene expression by Watson-Crick pairing to a target mRNA and altering expression by mechanisms related to RNA interference. The high sequence homology of plant miRNAs to their targets has been the mainstay of miRNA prediction algorithms, which are limited in their predictive power for other kingdoms because miRNA complementarity is less conserved yet transitive processes (production of antisense smRNAs) are active in eukaryotes. We hypothesize that antisense transcription and associated smRNAs are biomarkers which can be computationally modeled for gene discovery. Principal Findings: We explored rice (Oryza sativa) sense and antisense gene expression in publicly available whole genome tiling array transcriptome data and sequenced smRNA libraries (as well as C. elegans) and found evidence of transitivity of MIRNA genes similar to that found in Arabidopsis. Statistical analysis of antisense transcript abundances, presence of antisense ESTs, and association with smRNAs suggests several hundred Arabidopsis 'orphan' hypothetical genes are noncoding RNAs. Consistent with this hypothesis, we found novel Arabidopsis homologues of some MIRNA genes on the antisense strand of previously annotated protein-coding genes. A Support Vector Machine (SVM) was applied using thermodynamic energy of binding plus novel expression features of sense/antisense transcription topology and siRNA abundances to build a prediction model of miRNA targets. The SVM when trained on targets could predict the "ancient" (deeply conserved) class of validated Arabidopsis MIRNA genes with an accuracy of 84%, and 76% for "new" rapidlyevolving MIRNA genes. Conclusions: Antisense and smRNA expression features and computational methods may identify novel MIRNA genes and other non-coding RNAs in plants and potentially other kingdoms, which can provide insight into antisense transcription, miRNA evolution, and post-transcriptional gene regulation. © 2010 Richardson et al.

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