Author Archives: schraib

Vaccine escape in 2013-4 and the hydropathic evolution of glycoproteins of A/H3N2 viruses

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Vaccine escape in 2013-4 and the hydropathic evolution of glycoproteins of A/H3N2 viruses
J. C. Phillips

More virulent strains of influenza virus subtypes H1N1 appeared widely in 2007 and H3N2 in 2011, and especially 2013-4, when the effectiveness of the H3N2 vaccine decreased nearly to zero. The amino acid differences of neuraminidase from prior less virulent strains appear to be small (<1%) when tabulated through sequence alignments and counting site identities and similarities. Here we show how analyzing fractal hydropathic forces responsible for neuraminidase globular compaction and modularity quantifies the mutational origins of increased virulence. It also predicts vaccine escape and specifies optimized targets for the 2015 H3N2 vaccine different from the WHO target. Unlike some earlier methods based on measuring hemagglutinin antigenic drift and ferret sera, which take several years, cover only a few candidate strains, and are ambiguous, the new methods are timely and can be completed, using NCBI and GISAID amino acid sequences only, in a few days.

Speciation, ecological opportunity, and latitude

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Speciation, ecological opportunity, and latitude
Dolph Schluter

Evolutionary hypotheses to explain the greater numbers of species in the tropics than the temperate zone include greater age and area, higher temperature and metabolic rates, and greater ecological opportunity. These ideas make contrasting predictions about the relationship between speciation processes and latitude, which I elaborate and evaluate. Available data suggest that per capita speciation rates are currently highest in the temperate zone, and that diversification rates (speciation minus extinction) are similar between latitudes. In contrast, clades whose oldest analyzed dates precede the Eocene thermal maximum, when the extent of the tropics was much greater than today, tend to show highest speciation and diversification rates in the tropics. These findings are consistent with age and area, which is alone among hypotheses in predicting a time trend. Higher recent speciation rates in the temperate zone than the tropics suggest an additional response to high ecological opportunity associated with low species diversity. These broad patterns are compelling but provide limited insights into underlying mechanisms, arguing that studies of speciation processes along the latitudinal gradient will be vital. Using threespine stickleback in depauperate northern lakes as an example, I show how high ecological opportunity can lead to rapid speciation. The results support a role for ecological opportunity in speciation, but its importance in the evolution of the latitudinal gradient remains uncertain. I conclude that per-capita evolutionary rates are no longer higher in the tropics than the temperate zone. Nevertheless, the vast numbers of species that have already accumulated in the tropics ensure that total rate of species production remains highest there. Thus, tropical evolutionary momentum helps to perpetuate the steep latitudinal biodiversity gradient.

Combining exome and gene expression datasets in one graphical model of disease to empower the discovery of disease mechanisms

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Combining exome and gene expression datasets in one graphical model of disease to empower the discovery of disease mechanisms
Aziz M. Mezlini, Fabio Fuligni, Adam Shlien, Anna Goldenberg

Identifying genes associated with complex human diseases is one of the main challenges of human genetics and computational medicine. To answer this question, millions of genetic variants get screened to identify a few of importance. To increase the power of identifying genes associated with diseases and to account for other potential sources of protein function aberrations, we propose a novel factor-graph based model, where much of the biological knowledge is incorporated through factors and priors. Our extensive simulations show that our method has superior sensitivity and precision compared to variant-aggregating and differential expression methods. Our integrative approach was able to identify important genes in breast cancer, identifying genes that had coding aberrations in some patients and regulatory abnormalities in others, emphasizing the importance of data integration to explain the disease in a larger number of patients.

Brain Transcriptional Profiles of Male Alternative Reproductive Tactics in Bluegill Sunfish

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Brain Transcriptional Profiles of Male Alternative Reproductive Tactics in Bluegill Sunfish

Charlyn Partridge, Matthew MacManes, Rosemary Knapp, Bryan Neff
doi: http://dx.doi.org/10.1101/025916

Bluegill sunfish are one of the classic systems for studying male alternative reproductive tactics (ARTs) in teleost fishes. In this species, there are two distinct life histories: parental and cuckolder, encompassing three reproductive tactics, parental, satellite, and sneaker. The parental tactic is fixed, whereas individuals who enter the cuckolder life history transition from the sneaker to the satellite tactic as they grow. For this study, we used RNAseq to characterize the brain transcriptome of the three male tactics during spawning to identify gene categories associated with each tactic and identify potential candidate genes influencing their different spawning behaviors. We found that sneaker males had higher levels of gene differentiation compared to the other two tactics, suggesting that life history does not exclusively drive differential gene expression. Sneaker males had high expression in ionotropic glutamate receptor genes, specifically AMPA receptors, which may be important for increased working spatial memory while attempting to cuckold nests in bluegill colonies. We also found significant expression differences in several candidate genes involved in ARTs that were previously identified in other species and suggest a previously undescribed role for cytosolic 5-nucleotidase II (nt5c2) in influencing parental male behavior during spawning.

Incomplete domestication of South American grain amaranth (Amaranthus caudatus) from its wild relatives

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Markus G Stetter, Thomas Müller, Karl Schmid
doi: http://dx.doi.org/10.1101/025866
Grain amaranth is a pseudo-cereal and an ancient crop of Central and South America. Of the three species of grain amaranth, Amaranthus caudatus is mainly grown in the Andean region. Several models of domestication were proposed including a domestication from the wild relatives A. hybridus or A. quitensis. To investigate the domestication history of A. caudatus and its relationship to the two wild relatives, we used genotyping-by-sequencing (GBS) to genotype 119 amaranth accessions from the Andean region. We determined the genome sizes of the three species and compared phenotypic variation in two domestication-related traits, seed size and seed color. We show that the population genetic analysis based on 9,485 SNPs revealed very little genetic differentiation between the two wild species, suggesting they are the same species, but a strong differentiation between wild and domesticated amaranths. A. caudatus has a higher genetic diversity than its wild relatives and about 10% of accessions showed a strong admixture between the wild and cultivated species suggesting recent gene flow. Genome sizes and seed sizes were not significantly different between wild and domesticated amaranths, although a genetically distinct cluster of Bolivian accessions had significantly larger seeds.

Hybridization capture using RAD probes (hyRAD), a new tool for performing genomic analyses on museum collection specimens.

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Hybridization capture using RAD probes (hyRAD), a new tool for performing genomic analyses on museum collection specimens.

Tomasz Suchan, Camille Pitteloud, Nadezhda Gerasimova, Anna Kostikova, Nils Arrigo, Mila Pajkovic, Michał Ronikier, Nadir Alvarez
bioRxiv doi: http://dx.doi.org/10.1101/025551

In the recent years, many protocols aimed at reproducibly sequencing reduced-genome subsets in non-model organisms have been published. Among them, RAD-sequencing is one of the most widely used. It relies on digesting DNA with specific restriction enzymes and performing size selection on the resulting fragments. Despite its utility, this method is of a limited use with degraded DNA samples, such as those isolated from museum specimens, as these are either less likely to harbor fragments long enough to comprise two restriction sites making possible ligation of the technical sequences required or performing size selection of the resulting fragments. In addition, RAD-sequencing also reveals a suboptimal technique when applied to an evolutionary scale larger than the intra-specific level, as polymophisms in the restriction sites cause loci dropout. Here, we address both of these limitations by a novel method called hybridization RAD (hyRAD). In this method, biotinylated RAD fragments, covering a random fraction of the genome, are used as baits for capturing homologous fragments from samples processed through a classical genomic shotgun sequencing protocol. This simple and cost- effective approach allows sequencing orthologous sequences even from highly degraded DNA samples, opening new avenues of research in the field of museum genomics. Not relying on the restriction site presence, it improves among-sample loci coverage, and can be applied to broader phylogenetic scales. In a trial study, hyRAD allowed us to obtain a large set of orthologous loci from fresh and museum samples from a non-model butterfly species, with over 10.000 single nucleotide polymorphisms present in all eight analyzed specimens, including 58 years old museum samples.

Genome wide estimates of mutation rates and spectrum in Schizosaccharomyces pombe indicate CpG sites are highly mutagenic despite the absence of DNA methylation

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Genome wide estimates of mutation rates and spectrum in Schizosaccharomyces pombe indicate CpG sites are highly mutagenic despite the absence of DNA methylation

Megan G Behringer, David W Hall
bioRxiv doi: http://dx.doi.org/10.1101/025601

We accumulated mutations for 1952 generations in 79 initially identical, haploid lines of the fission yeast Schizosaccharomyces pombe and then performed whole-genome sequencing to determine the mutation rates and spectrum. We captured 696 spontaneous mutations across the 79 mutation accumulation lines. We compared the mutation spectrum and rate to another model ascomycetous yeast, the budding yeast Saccharomyces cerevisiae. While the two organisms are approximately 600 million years diverged from each other, they share similar life histories, genome size and genomic G/C content. We found that Sc. pombe and S. cerevisiae have similar mutation rates, contrary to what was expected given Sc. pombe’s smaller reported effective population size. Sc. pombe’s also exhibits a strong insertion bias in comparison to S. cerevisiae,. Intriguingly, we observed an increased mutation rate at cytosine nucleotides, specifically CpG nucleotides, which is also seen in S. cerevisiae. However, the absence of methylation in Sc. pombe and the pattern of mutation at these sites, primarily C→ A as opposed to C→T, strongly suggest that the increased mutation rate is not caused by deamination of methylated cytosines. This result implies that the high mutability of CpG dinucleotides in other species may be caused in part by an additional mechanism than methylation.

Implications of simplified linkage equilibrium SNP simulation

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Implications of simplified linkage equilibrium SNP simulation

Sang Hong Lee
bioRxiv doi: http://dx.doi.org/10.1101/025619

In a recent paper published in PNAS (Golan et al. 2014), residual maximum likelihood (REML) seriously underestimated genetic variance explained by genomewide single nucleotide polymorphism when using a case-control design. It was concluded that Haseman–Elston regression (denoted as PCGC in their paper) should be used instead of REML. Their conclusions were based on results from simplified linkage equilibrium SNP simulation (SLES), which the authors acknowledged may be unrealistic. We found that their simulation, SLES, unrealistically inflated the correlation between the eigenvectors of the genomic relationship matrix and disease status to values that are rarely observed in real data analyses. With a more realistic simulation that the authors failed to carry out (as they noted in their paper), we showed that there was no such inflated correlation between the eigenvectors of the genomic relationship matrix and disease status. Because REML uses the eigensystem of covariance structure, the inflated correlation artefactually constrained its estimates. We compared SNP-heritabilities from SLES and a more realistic simulation, showing that there was a substantial difference between the REML estimates from the two simulation strategies. Finally, we presented that there was no difference between REML and PCGC in real data analyses. This pattern from real data results differed strikingly from the pattern in the simulation study of Golan et al. One needs to be cautious of results drawn from SLES.

DNA-metabarcoding uncovers the diversity of soil-inhabiting fungi in the tropical island of Puerto Rico

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DNA-metabarcoding uncovers the diversity of soil-inhabiting fungi in the tropical island of Puerto Rico

Hector Urbina, Douglas G. Scofield, Matias Cafaro, Anna Rosling
bioRxiv doi: http://dx.doi.org/10.1101/025668
Soil fungal communities in tropical regions remain poorly understood. In order to increase the knowledge of diversity of soil-inhabiting fungi, we extracted total DNA from top-organic soil collected in seven localities dominated by four major ecosystems in the tropical island of Puerto Rico. In order to comprehensively characterize the fungal community, we PCR-amplified the ITS2 fungal barcode using newly designed degenerated primers and varying annealing temperatures to minimize primer bias. Sequencing results, obtained using Ion Torrent technology, comprised a total of 566,613 sequences after quality filtering. These sequences were clustered into 4,140 molecular operational taxonomic units (MOTUs) after removing low frequency sequences and rarefaction to account for differences in read depth between samples. Our results demonstrate that soil fungal communities in Puerto Rico are structured by ecosystem. Ascomycota, followed by Basidiomycota, dominates the diversity of fungi in soil. Amongst Ascomycota, the recently described soil-inhabiting class Archaeorhizomycetes was present in all the localities and taxa in this class were among the most commonly observed MOTUs. The Basidiomycota community was dominated by soil decomposers and ectomycorrhizal fungi with a distribution strongly affected by local variation to a greater degree than Ascomycota.

The site-frequency spectrum associated with Xi-coalescents

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The site-frequency spectrum associated with Xi-coalescents

Jochen Blath, Mathias C Cronjager, Bjarki Eldon, Matthias Hammer
bioRxiv doi: http://dx.doi.org/10.1101/025684
We give recursions for the expected site-frequency spectrum associated with Xi-coalescents, that is exchangeable coalescents which admit simultaneous multiple mergers of ancestral lineages. Xi-coalescents arise, for example, in association with population models of skewed offspring distributions with diploidy, recurrent advantageous mutations, or strong bottlenecks. In contrast, Lambda-coalescents admit multiple mergers of lineages, but at most one such merger each time. Xi-coalescents, as well as Lambda-coalescents, can predict an excess of singletons, compared to the Kingman coalescent. We compare estimates of coalescent parameters when Xi-coalescent models are applied to data obtained from Lambda-coalescents, and vice versa. In general, Xi-coalescents predict fewer singletons than corresponding Lambda-coalescents, but higher count of mutations of `size’ larger than singletons. We analyse unfolded site-frequency spectra obtained for nuclear loci of the diploid Atlantic cod, and obtain different coalescent parameter estimates than previously obtained with Lambda-coalescents. Our results provide new inference tools, and suggest that for nuclear population genetic data from diploid or polyploid highly fecund populations who may have skewed offspring distributions, one should not apply Lambda-coalescents, but Xi-coalescents.