A long journey to reproducible results

Nature  

2017-08-22

Replicating our work took four years and 100,000 worms but brought surprising discoveries, explain Gordon J. Lithgow, Monica Driscoll and Patrick Phillips.

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Science talk draws a large crowd to hear about Knight Campus

Around the O  online

2017-05-15

A science talk by UO’s Patrick Phillips, “Science at the Nexus of Life and Death,” drew more than 400 members of the local community to the John G. Shedd Institute for the Arts last Tuesday evening.

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New York Worms Have 'killer Sperm': Females Live Half as Long After Mating With Males From the City Than in Other Areas

Daily Mail  online

2015-06-02

Professor Patrick Phillips, a biologist who led the research at the University of Oregon, said the discovery has left them baffled as to why such a trait would have evolved. He said: 'It could be a change in the behaviour of the males, or it could be something in the seminal fluid that they transfer during mating. 'Despite their small size, nematode sperm is actually much larger than human sperm, and it is thought that the sperm from different males battle it out inside the female for access to her eggs.'...

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In-Depth Look at History’s Largest Genetic Twin Study

Bioscience Technology  online

2015-05-27

The largest meta-study of twins in history—which examined 14.5 million sets of twins — found that, generally, genes and environment play an equal role in human development. “If we pool all data, the balance between nature and nurture is near perfect: across all traits the heritability is 49 percent, and environmental influences account for 51 percent,” senior author Danielle Posthuma, Ph.D., Neuroscience Campus Amsterdam Complex Trait Genetics department head, told Bioscience Technology. University of Oregon biologist Patrick Phillips, Ph.D., also uninvolved in the study, told Bioscience Technology he was “completely blown away” by the size of it, and that it was “fascinating, if it doesn’t really tell us about gene function per se.” But, he said, “It does tell us something about the genetic basis of these traits. And by and large it is consistent with genome-wide association studies (GWAS). It seems that most complex states are caused by many, many genes with fairly small effects. And when that is true, you expect that most overall effects would be caused by adding up those genes together, the general pattern people have been discovering over the past five or six years.”

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UO Study Finds New York Males Are Deadly -- in the World of Roundworms

Around the O  online

2015-05-28

Scientific ideas often take time to grow. For UO biologist Patrick Phillips, an observation of a graduate student more than 10 years ago planted a seed of curiosity. Why were female roundworms — nematodes known scientifically as Caenorhabditis remanei — dying more quickly after mating with males originally collected from New York than those that mated to males from other places? Former master's degree student Colin Peden, who studied at the UO from 2001 to 2004, raised that question with Phillips. Peden has since moved on, initially as a doctoral student at the University of Texas at Austin. He's now a musician in San Francisco. Phillips pondered the mystery and began a series of experiments while seeking outside help. His efforts were delayed briefly while he served as the UO's associate vice president for research. Finally, he turned to Michael Palopoli, an evolutionary biologist at Bowdoin College in Brunswick, Maine. Their two labs went to work. This month, in a study placed online by BioMed Central's open-access journal BMC Evolutionary Biology, the researchers provided some answers related to sexual competition, sperm size and the behavior of C. remanei males.

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Presence of Opposite Sex Can Shorten Life Span

ScienceMag.org  online

2013-11-29

The finding poses an evolutionary puzzle. Hermaphrodites fertilize their own eggs, but males can sire offspring only by mating with hermaphrodites. So why do males kill the mothers of their babies? One possible reason, Brunet says, is competition among males. A male might trigger the demise of his mate to prevent other males from mating with her. However, Patrick Phillips, an evolutionary geneticist at the University of Oregon in Eugene, says he doubts that nematode males are manipulating hermaphrodites, because the hermaphrodites still live long enough to produce a normal number of offspring. Nevertheless, Phillips says the papers break new ground. “We’ve known for a long time that mating can be harmful,” he says. But these papers show that “you can have the effects without direct physical contact.” Sean Curran, a biogerontologist at the University of Southern California in Los Angeles, predicts the animals’ ability to influence life span “is going to be a hot topic for discussion for quite a while.” Whether one sex shortens the lives of people or other vertebrates remains uncertain, and finding out will be tricky, Curran cautions: “It’s a far more complicated question in a mammal.” Indeed, in his angst-laden song, Meat Loaf lives on, reduced to merely “praying for the end of time so I can end my time with you.”

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DNA at 60: Still Much to Learn

Scientific American  online

2013-04-28

According to evolutionary biologist Patrick Phillips at the University of Oregon in Eugene, projects such as ENCODE are showing scientists that they don't really understand how genotypes map to phenotypes, or how exactly evolutionary forces shape any given genome.

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Metagenome-assembled draft genome sequence of a novel microbial Stenotrophomonas maltophilia strain isolated from Caenorhabditis remanei tissue

2017 Stenotrophomonas maltophilia is a Gram-negative aerobic bacterium and emerging nosocomial pathogen. Here, we present a draft genome sequence for an S. maltophilia strain assembled from a metagenomic DNA extract isolated from a laboratory stock of the nematode worm Caenorhabditis remanei.

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Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects

2017 Limiting the debilitating consequences of ageing is a major medical challenge of our time. Robust pharmacological interventions that promote healthy ageing across diverse genetic backgrounds may engage conserved longevity pathways. Here we report results from the Caenorhabditis Intervention Testing Program in assessing longevity variation across 22 Caenorhabditis strains spanning 3 species, using multiple replicates collected across three independent laboratories. Reproducibility between test sites is high, whereas individual trial reproducibility is relatively low. Of ten pro-longevity chemicals tested, six significantly extend lifespan in at least one strain. Three reported dietary restriction mimetics are mainly effective across C. elegans strains, indicating species and strain-specific responses. In contrast, the amyloid dye ThioflavinT is both potent and robust across the strains. Our results highlight promising pharmacological leads and demonstrate the importance of assessing lifespans of discrete cohorts across repeat studies to capture biological variation in the search for reproducible ageing interventions.

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Coevolutionary interactions with parasites constrain the spread of self‐fertilization into outcrossing host populations

2016 Given the cost of sex, outcrossing populations should be susceptible to invasion and replacement by self-fertilization or parthenogenesis. However, biparental sex is common in nature, suggesting that cross-fertilization has substantial short-term benefits. The Red Queen hypothesis (RQH) suggests that coevolution with parasites can generate persistent selection favoring both recombination and outcrossing in host populations. We tested the prediction that coevolving parasites can constrain the spread of self-fertilization relative to outcrossing. We introduced wild-type Caenorhabditis elegans hermaphrodites, capable of both self-fertilization, and outcrossing, into C. elegans populations that were fixed for a mutant allele conferring obligate outcrossing. Replicate C. elegans populations were exposed to the parasite Serratia marcescens for 33 generations under three treatments: a control (avirulent) parasite treatment, a fixed (nonevolving) parasite treatment, and a copassaged (potentially coevolving) parasite treatment. Self-fertilization rapidly invaded C. elegans host populations in the control and the fixed-parasite treatments, but remained rare throughout the entire experiment in the copassaged treatment. Further, the frequency of the wild-type allele (which permits selfing) was strongly positively correlated with the frequency of self-fertilization across host populations at the end of the experiment. Hence, consistent with the RQH, coevolving parasites can limit the spread of self-fertilization in outcrossing populations.

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Comparative genomic analysis of upstream miRNA regulatory motifs in Caenorhabditis

2016 MicroRNAs (miRNAs) comprise a class of short noncoding RNA molecules that play diverse developmental and physiological roles by controlling mRNA abundance and protein output of the vast majority of transcripts. Despite the importance of miRNAs in regulating gene function, we still lack a complete understanding of how miRNAs themselves are transcriptionally regulated. To fill this gap, we predicted regulatory sequences by searching for abundant short motifs located upstream of miRNAs in eight species of Caenorhabditis nematodes. We identified three conserved motifs across the Caenorhabditis phylogeny that show clear signatures of purifying selection from comparative genomics, patterns of nucleotide changes in motifs of orthologous miRNAs, and correlation between motif incidence and miRNA expression. We then validated our predictions with transgenic green fluorescent protein reporters and site-directed mutagenesis for a subset of motifs located in an enhancer region upstream of let-7. We demonstrate that a CT-dinucleotide motif is sufficient for proper expression of GFP in the seam cells of adult C. elegans, and that two other motifs play incremental roles in combination with the CT-rich motif. Thus, functional tests of sequence motifs identified through analysis of molecular evolutionary signatures provide a powerful path for efficiently characterizing the transcriptional regulation of miRNA genes.

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High-specificity detection of rare alleles with Paired-End Low Error Sequencing (PELE-Seq)

2016 Background Polymorphic loci exist throughout the genomes of a population and provide the raw genetic material needed for a species to adapt to changes in the environment. The minor allele frequencies of rare Single Nucleotide Polymorphisms (SNPs) within a population have been difficult to track with Next-Generation Sequencing (NGS), due to the high error rate of standard methods such as Illumina sequencing. Results We have developed a wet-lab protocol and variant-calling method that identifies both sequencing and PCR errors, called Paired-End Low Error Sequencing (PELE-Seq). To test the specificity and sensitivity of the PELE-Seq method, we sequenced control E. coli DNA libraries containing known rare alleles present at frequencies ranging from 0.2–0.4 % of the total reads. PELE-Seq had higher specificity and sensitivity than standard libraries. We then used PELE-Seq to characterize rare alleles in a Caenorhabditis remanei nematode worm population before and after laboratory adaptation, and found that minor and rare alleles can undergo large changes in frequency during lab-adaptation. Conclusion We have developed a method of rare allele detection that mitigates both sequencing and PCR errors, called PELE-Seq. PELE-Seq was evaluated using control E. coli populations and was then used to compare a wild C. remanei population to a lab-adapted population. The PELE-Seq method is ideal for investigating the dynamics of rare alleles in a broad range of reduced-representation sequencing methods, including targeted amplicon sequencing, RAD-Seq, ddRAD, and GBS. PELE-Seq is also well-suited for whole genome sequencing of mitochondria and viruses, and for high-throughput rare mutation screens.

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