Yearly Archives: 2015

RNAseq in the mosquito maxillary palp: a little antennal RNA goes a long way

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RNAseq in the mosquito maxillary palp: a little antennal RNA goes a long way

David C. Rinker , Xiaofan Zhou , Ronald Jason Pitts , Antonis Rokas , LJ Zwiebel
doi: http://dx.doi.org/10.1101/016998

A comparative transcriptomic study of mosquito olfactory tissues recently published in BMC Genomics (Hodges et al., 2014) reported several novel findings that have broad implications for the field of insect olfaction. In this brief commentary, we outline why the conclusions of Hodges et al. are problematic under the current models of insect olfaction and then contrast their findings with those of other RNAseq based studies of mosquito olfactory tissues. We also generated a new RNAseq data set from the maxillary palp of Anopheles gambiae in an effort to replicate the novel results of Hodges et al. but were unable to reproduce their results. Instead, our new RNAseq data support the more straightforward explanation that the novel findings of Hodges et al. were a consequence of contamination by antennal RNA. In summary, we find strong evidence to suggest that the conclusions of Hodges et al were spurious, and that at least some of their RNAseq data sets were irrevocably compromised by cross-contamination between samples.

Selective strolls: fixation and extinction in diploids are slower for weakly selected mutations than for neutral ones

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Selective strolls: fixation and extinction in diploids are slower for weakly selected mutations than for neutral ones

fabrizio mafessoni , Michael Lachmann
doi: http://dx.doi.org/10.1101/016881

In finite populations, an allele disappears or reaches fixation due to two main forces, selection and drift. Selec- tion is generally thought to accelerate the process: a selected mutation will reach fixation faster than a neutral one, and a disadvantageous one will quickly disappear from the population. We show that even in simple diploid populations, this is often not true. Dominance and recessivity unexpectedly slow down the evolutionary process for weakly selected alleles. In particular, slightly advantageous dominant and mildly deleterious recessive mu- tations reach fixation more slowly than neutral ones. This phenomenon determines genetic signatures opposite to those expected under strong selection, such as increased instead of decreased genetic diversity around the selected site. Furthermore, we characterize a new phenomenon: mildly deleterious recessive alleles, thought to represent the vast majority of newly arising mutations, survive in a population longer than neutral ones, before getting lost. Hence, natural selection is less effective than previously thought in getting rid rapidly of slightly negative mutations, contributing their observed persistence in present populations. Consequently, low frequency slightly deleterious mutations are on average older than neutral ones.

Variation in rural African gut microbiomes is strongly shaped by parasitism and diet

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Variation in rural African gut microbiomes is strongly shaped by parasitism and diet

Elise R Morton , Joshua Lynch , Alain Froment , Sophie Lafosse , Evelyne Heyer , Molly Przeworski , Ran Blekhman , Laure Segurel
doi: http://dx.doi.org/10.1101/016949

The human gut microbiome is influenced by its host’s nutrition and health status, and represents an interesting adaptive phenotype under the influence of metabolic and immune constraints. Previous studies contrasting rural populations in developing countries to urban industrialized ones have shown that geography is an important factor associated with the gut microbiome; however, studies have yet to disentangle the effects of factors such as climate, diet, host genetics, hygiene and parasitism. Here, we focus on fine-scale comparisons of African rural populations in order to (i) contrast the gut microbiomes of populations that inhabit similar environments but have different traditional subsistence modes and (ii) evaluate the effect of parasitism on microbiome composition and structure. We sampled rural Pygmy hunter-gatherers as well as Bantu individuals from both farming and fishing populations in Southwest Cameroon and found that the presence of Entamoeba is strongly correlated with microbial composition and diversity. Using a random forest classifier model, we show that an individual’s infection status can be predicted with 79% accuracy based on his/her gut microbiome composition. We identified multiple taxa that differ significantly in frequency between infected and uninfected individuals, and found that alpha diversity is significantly higher in infected individuals, while beta-diversity is reduced. Subsistence mode was another factor significantly associated with microbial composition, notably with some taxa previously shown to differ between Hadza East African hunter-gatherers and Italians also discriminating Pygmy hunter-gatherers from neighboring farming or fishing populations in Cameroon. In conclusion, these results provide evidence for a strong relationship between human gut parasites and the microbiome, and highlight how sensitive this microbial ecosystem is to subtle changes in host nutrition.

The origins of a novel butterfly wing patterning gene from within a family of conserved cell cycle regulators

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The origins of a novel butterfly wing patterning gene from within a family of conserved cell cycle regulators

Nicola Nadeau , Carolina Pardo-Diaz , Annabel Whibley , Megan Ann Supple , Richard Wallbank , Grace C. Wu , Luana Maroja , Laura Ferguson , Heather Hines , Camilo Salazar , Richard ffrench-Constant , Mathieu Joron , William Owen McMillan , Chris Jiggins
doi: http://dx.doi.org/10.1101/016006

A major challenge in evolutionary biology is to understand the origins of novel structures. The wing patterns of butterflies and moths are derived phenotypes unique to the Lepidoptera. Here we identify a gene that we name poikilomousa (poik), which regulates colour pattern switches in the mimetic Heliconius butterflies. Strong associations between phenotypic variation and DNA sequence variation are seen in three different Heliconius species, in addition to associations between gene expression and colour pattern. Colour pattern variants are also associated with differences in splicing of poik transcripts. poik is a member of the conserved fizzy family of cell cycle regulators. It belongs to a faster evolving subfamily, the closest functionally characterised orthologue being the cortex gene in Drosophila, a female germ-line specific protein involved in meiosis. poik appears to have adopted a novel function in the Lepidoptera and become a major target for natural selection acting on colour and pattern variation in this group.

Recombining without hotspots: A comprehensive evolutionary portrait of recombination in two closely related species of Drosophila

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Recombining without hotspots: A comprehensive evolutionary portrait of recombination in two closely related species of Drosophila

Caiti Smukowski Heil , Chris Ellison , Matthew Dubin , Mohamed Noor
doi: http://dx.doi.org/10.1101/016972

Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in Metazoans by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present what may be the most comprehensive portrait of recombination to date, combining contemporary recombination estimates from each of two sister species along with historic estimates of recombination using linkage-disequilibrium-based approaches derived from sequence data from both species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we replicate the pattern seen in human-chimpanzee that recombination rate is conserved at broad scales and more divergent at finer scales. We also find evidence of a species-wide recombination modifier, resulting in both a present and historic genome wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inter-species inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms.

Repeatability of evolution on epistatic landscapes

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Repeatability of evolution on epistatic landscapes
Benedikt Bauer , Chaitanya S Gokhale
doi: http://dx.doi.org/10.1101/016782

Evolution is a dynamic process. The two classical forces of evolution are mutation and selection. Assuming small mutation rates, evolution can be predicted based solely on the fitness differences between phenotypes. Predicting an evolutionary process under varying mutation rates as well as varying fitness is still an open question. Experimental procedures, however, do include these complexities along with fluctuating population sizes and stochastic events such as extinctions. We investigate the mutational path probabilities of systems having epistatic effects on both fitness and mutation rates using a theoretical and computational framework. In contrast to previous models, we do not limit ourselves to the typical strong selection, weak mutation (SSWM)-regime or to fixed population sizes. Rather we allow epistatic interactions to also affect mutation rates. This can lead to qualitatively non-trivial dynamics. Pathways, that are negligible in the SSWM-regime, can overcome fitness valleys and become accessible. This finding has the potential to extend the traditional predictions based on the SSWM foundation and bring us closer to what is observed in experimental systems.

SumVg: Total heritability explained by all variants in genome-wide association studies based on summary

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SumVg: Total heritability explained by all variants in genome-wide association studies based on summary statistics with standard error estimates
Hon-Cheong SO , Pak C. SHAM
doi: http://dx.doi.org/10.1101/016857

Genome-wide association studies (GWAS) have become increasingly popular these days and one of the key questions is how much heritability could be explained by all variants in GWAS. We have previously proposed an approach to answer this question, based on recovering the “true” z-statistics from a set of observed z-statistics. Only summary statistics are required. However, methods for standard error (SE) estimation are not available yet, thereby limiting the interpretation of the results. In this study we developed resampling-based approaches to estimate the SE and the methods are implemented in an R package. We found that delete-d-jackknife and parametric bootstrap approaches provide good estimates of the SE. Methods to compute the sum of heritability explained and the corresponding SE are implemented in the R package SumVg, available at https://sites.google.com/site/honcheongso/software/var-totalvg

The advent of genome-wide association studies for bacteria

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The advent of genome-wide association studies for bacteria
Peter E Chen , B Jesse Shapiro
doi: http://dx.doi.org/10.1101/016873

Significant advances in sequencing technologies and genome-wide association studies (GWAS) have revealed substantial insight into the genetic architecture of human phenotypes. In recent years, the application of this approach in bacteria has begun to reveal the genetic basis of bacterial host preference, antibiotic resistance, and virulence. Here, we consider relevant differences between bacterial and human genome dynamics, apply GWAS to a global sample of Mycobacterium tuberculosis genomes to highlight the impacts of linkage disequilibrium, population stratification, and natural selection, and finally compare the traditional GWAS against phyC, a contrasting method of mapping genotype to phenotype based upon evolutionary convergence. We discuss strengths and weaknesses of both methods, and make suggestions for factors to be considered in future bacterial GWAS.

Cline coupling and uncoupling in a stickleback hybrid zone

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Cline coupling and uncoupling in a stickleback hybrid zone
Tim Vines , Anne Dalziel , Arianne Albert , Thor Veen , Patricia Schulte , Dolph Schluter
doi: http://dx.doi.org/10.1101/016832

Strong ecological selection on a genetic locus can maintain allele frequency differences between populations in different environments, even in the face of hybridization. When alleles at divergent loci come into tight linkage disequilibria, selection acts on them as a unit and can significantly reduce gene flow. For populations interbreeding across a hybrid zone, linkage disequilibria between loci can force clines to share the same slopes and centers. However, strong ecological selection can push clines away from the others, reducing linkage disequilibria and weakening the barrier to gene flow. We looked for this ‘cline uncoupling’ effect in a hybrid zone between stream resident and anadromous sticklebacks at two genes known to be under divergent natural selection (Eda and ATP1a1) and five morphological traits that repeatedly evolve in freshwater stickleback. We used 10 anonymous SNPs to characterize the shape of the zone. We found that the clines at Eda, ATP1a1, and four morphological traits were concordant and coincident, suggesting that direct selection on each is outweighed by the indirect selection generated by linkage disequilibria. Interestingly, the cline for pectoral fin length was much steeper and displaced 200m downstream, and two anonymous SNPs also had steep clines.

Exploring functional variation affecting ceRNA regulation in humans

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Exploring functional variation affecting ceRNA regulation in humans
Mulin Jun Li , Jiexing Wu , Peng Jiang , Wei Li , Yun Zhu , Daniel Fernandez , Russell J. H. Ryan , Yiwen Chen , Junwen Wang , Jun S. Liu , X. Shirley Liu
doi: http://dx.doi.org/10.1101/016865

MicroRNA (miRNA) sponges have been shown to function as competing endogenous RNAs (ceRNAs) to regulate the expression of other miRNA targets in the network by sequestering available miRNAs. As the first systematic investigation of the genome-wide genetic effect on ceRNA regulation, we applied multivariate response regression and identified widespread genetic variations that are associated with ceRNA competition using 462 Geuvadis RNA-seq data in multiple human populations. We showed that SNPs in gene 3’UTRs at the miRNA seed binding regions can simultaneously regulate gene expression changes in both cis and trans by the ceRNA mechanism. We termed these loci as endogenous miRNA sponge expression quantitative trait loci or “emsQTLs”, and found that a large number of them were unexplored in conventional eQTL mapping. We identified many emsQTLs are undergoing recent positive selection in different human populations. Using GWAS results, we found that emsQTLs are significantly enriched in traits/diseases associated loci. Functional prediction and prioritization extend our understanding on causality of emsQTL allele in disease pathways. We illustrated that emsQTL can synchronously regulate the expression of tumor suppressor and oncogene through ceRNA competition in angiogenesis. Together these results provide a distinct catalog and characterization of functional noncoding regulatory variants that control ceRNA crosstalk.