Yearly Archives: 2015

Transcriptome Differences between Alternative Sex Determining Genotypes in the House Fly, Musca domestica

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Transcriptome Differences between Alternative Sex Determining Genotypes in the House Fly, Musca domestica
Richard P Meisel , Jeffrey G Scott , Andrew G Clark
doi: http://dx.doi.org/10.1101/016774

Sex determination evolves rapidly, often because of turnover of the genes at the top of the pathway. The house fly, Musca domestica, has a multifactorial sex determination system, allowing us to identify the selective forces responsible for the evolutionary turnover of sex determination in action. There is a male determining factor, M, on the Y chromosome (YM), which is probably the ancestral state. An M factor on the third chromosome (IIIM) has reached high frequencies in multiple populations across the world, but the evolutionary forces responsible for the invasion of IIIM are not resolved. To test if the IIIM chromosome invaded because of sex-specific selection pressures, we used mRNA sequencing to determine if isogenic males that differ only in the presence of the YM or IIIM chromosome have different gene expression profiles. We find that more genes are differentially expressed between YM and IIIM males in testis than head, and that genes with male-biased expression are most likely to be differentially expressed between YM and IIIM males. This suggests that male phenotypes, especially those related to male fertility, are more likely to be affected by the male-determining chromosome, supporting the hypothesis that sex-specific selection acts on alleles linked to the male-determining locus driving evolutionary turnover in the sex determination pathway. We additionally find that IIIM males have a “masculinized” gene expression profile, suggesting that the IIIM chromosome has accumulated an excess of male- beneficial alleles because of its male-limited transmission.

Breaking through evolutionary constraint by environmental fluctuations

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Breaking through evolutionary constraint by environmental fluctuations
Marjon GJ de Vos , Alexandre Dawid , Vanda Sunderlikova , Sander J Tans
doi: http://dx.doi.org/10.1101/016790

Epistatic interactions can frustrate and shape evolutionary change. Indeed, phenotypes may fail to evolve because essential mutations can only be selected positively if fixed simultaneously. How environmental variability affects such constraints is poorly understood. Here we studied genetic constraints in fixed and fluctuating environments, using the Escherichia coli lac operon as a model system for genotype-environment interactions. The data indicated an apparent paradox: in different fixed environments, mutational trajectories became trapped at sub-optima where no further improvements were possible, while repeated switching between these same environments allowed unconstrained adaptation by continuous improvements. Pervasive cross-environmental trade-offs transformed peaks into valleys upon environmental change, thus enabling escape from entrapment. This study shows that environmental variability can lift genetic constraint, and that trade-offs not only impede but can also facilitate adaptive evolution.

The fate of a mutation in a fluctuating environment

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The fate of a mutation in a fluctuating environment

Ivana Cvijovic , Benjamin H. Good , Elizabeth R. Jerison , Michael M. Desai
doi: http://dx.doi.org/10.1101/016709

Natural environments are never truly constant, but the evolutionary implications of temporally varying selection pressures remain poorly understood. Here we investigate how the fate of a new mutation in a variable environment depends on the dynamics of environmental fluctuations and on the selective pressures in each condition. We find that even when a mutation experiences many environmental epochs before fixing or going extinct, its fate is not necessarily determined by its time-averaged selective effect. Instead, environmental variability reduces the efficiency of selection across a broad parameter regime, rendering selection unable to distinguish between mutations that are substantially beneficial and substantially deleterious on average. Temporal fluctuations can also dramatically increase fixation probabilities, often making the details of these fluctuations more important than the average selection pressures acting on each new mutation. For example, mutations that result in a tradeoff between conditions but are strongly deleterious on average can nevertheless be more likely to fix than mutations that are always neutral or beneficial. These effects can have important implications for patterns of molecular evolution in variable environments, and they suggest that it may often be difficult for populations to maintain specialist traits, even when their loss leads to a decline in time-averaged fitness.

Dimensionality and the statistical power of multivariate genome-wide association studies

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Dimensionality and the statistical power of multivariate genome-wide association studies

Eladio J. Marquez , David Houle
doi: http://dx.doi.org/10.1101/016592

Mutations virtually always have pleiotropic effects, yet most genome-wide association studies (GWAS) analyze effects one trait at a time. In order to investigate the performance of a multivariate approach to GWAS, we simulated scenarios where variation in a d-dimensional phenotype space was caused by a known subset of SNPs. Multivariate analyses of variance were then carried out on k traits, where k could be less than, greater than or equal to d. Our results show that power is maximized and false discovery rate (FDR) minimized when the number of traits analyzed, k, matches the true dimensionality of the phenotype being analyzed, d. When true dimensionality is high, the power of a single univariate analysis can be an order of magnitude less than the k=d case, even when the single trait with the largest genetic variance is chosen for analysis. When traits are added to a study in order of their independent genetic variation, the gains in power from increasing k up to d are much larger than the loss in power when k exceeds d. Simulations that explicitly model linkage disequilibrium (LD) indicate that when SNPs in disequilibrium are subjected to multivariate analysis, the magnitude of the apparent effect induced onto null SNPs by SNPs carrying a true effect weakens as k approaches d, such that the rank of P-values among a set of correlated SNPs becomes an increasingly reliable predictor of true positives. Multivariate GWAS outperform univariate ones under a wide range of conditions, and should become the standard in studies of the inheritance of complex phenotypes.

Analysis of whole mitogenomes from ancient samples

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Analysis of whole mitogenomes from ancient samples

Gloria G. Fortes, Johanna L.A. Paijmans
(Submitted on 17 Mar 2015)

Ancient mitochondrial DNA has been used in a wide variety of palaeontological and archaeological studies, ranging from population dynamics of extinct species to patterns of domestication. Most of these studies have traditionally been based on the analysis of short fragments from the mitochondrial control region, analysed using PCR coupled with Sanger sequencing. With the introduction of high-throughput sequencing, as well as new enrichment technologies, the recovery of full mitochondrial genomes (mitogenomes) from ancient specimens has become significantly less complicated. Here we present a protocol to build ancient extracts into Illumina high-throughput sequencing libraries, and subsequent Agilent array-based capture to enrich for the desired mitogenome. Both are based on previously published protocols, with the introduction of several improvements aimed to increase the recovery of short DNA fragments, while keeping the cost and effort requirements low. This protocol was designed for enrichment of mitochondrial DNA in ancient or degraded samples. However, the protocols can be easily adapted for using for building libraries for shotgun-sequencing of whole genomes, or enrichment of other genomic regions.

Structured nucleosome fingerprints enable high-resolution mapping of chromatin architecture within regulatory regions

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Structured nucleosome fingerprints enable high-resolution mapping of chromatin architecture within regulatory regions

Alicia Schep , Jason D Buenrostro , Sarah K Denny , Katja Schwartz , Gavin Sherlock , William J Greenleaf
doi: http://dx.doi.org/10.1101/016642

Transcription factors canonically bind nucleosome-free DNA, making the positioning of nucleosomes within regulatory regions crucial to the regulation of gene expression. We observe a highly structured pattern of DNA fragment lengths and positions generated by the assay of transposase accessible chromatin (ATAC-seq) around nucleosomes in S. cerevisiae, and use this distinctive two-dimensional nucleosomal “fingerprint” as the basis for a new nucleosome-positioning algorithm called NucleoATAC. We show that NucleoATAC can identify the rotational and translational positions of nucleosomes with up to base pair resolution and provide quantitative measures of nucleosome occupancy in S. cerevisiae, S. pombe, and human cells. We demonstrate application of NucleoATAC to a number of outstanding problems in chromatin biology, including analysis of sequence features underlying nucleosome positioning, promoter chromatin architecture across species, identification of transient changes in nucleosome occupancy and positioning during a dynamic cellular response, and integrated analysis of nucleosome occupancy and transcription factor binding.

Pollen-specific genes accumulate more deleterious mutations than sporophytic genes under relaxed purifying selection in Arabidopsis thaliana.

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Pollen-specific genes accumulate more deleterious mutations than sporophytic genes under relaxed purifying selection in Arabidopsis thaliana.

Mark Christian Harrison , Eamonn B Mallon , Dave Twell , Robert L Hammond
doi: http://dx.doi.org/10.1101/016626

The strength of purifying selection varies among loci and leads to differing frequencies of deleterious alleles within genomes. Selection is generally stronger for highly and broadly expressed genes but can be less efficient for diploid expressed, deleterious alleles if heterozygous. In plants expression level, tissue specificity and ploidy level differ between pollen specific and sporophyte specific genes. This may explain why the reported strength and direction of the relationship between selection and the specificity of a gene to either pollen or sporophytic tissues varies between studies and species. In this study, we investigate the individual effects of expression level and tissue specificity on selection efficacy within pollen genes and sporophytic genes of Arabidopsis thaliana. Due to high homozygosity levels caused by selfing, masking is expected to play a lesser role. We find that expression level and tissue specificity independently influence selection in A. thaliana. Furthermore, contrary to expectations, pollen genes are evolving faster due to relaxed purifying selection and have accumulated a higher frequency of deleterious alleles. This suggests that high homozygosity levels resulting from high selfing rates reduce the effects of pollen competition and masking in A. thaliana, so that the high tissue specificity and expression noise of pollen genes are leading to lower selection efficacy compared to sporophyte genes.

Sex chromosome dosage compensation in Heliconius butterflies: global yet still incomplete?

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Sex chromosome dosage compensation in Heliconius butterflies: global yet still incomplete?

James R Walters , Thomas J Hardcastle , Chris Jiggins
doi: http://dx.doi.org/10.1101/016675

The evolution of heterogametic sex chromosome is often – but not always – accompanied by the evolution of dosage compensating mechanisms that mitigate the impact of sex-specific gene dosage on levels of gene expression. One emerging view of this process is that such mechanisms may only evolve in male-heterogametic (XY) species but not in female-heterogametic (ZW) species, which will consequently exhibit “incomplete” sex chromosome dosage compensation. However, some recent results from moths suggest that Lepidoptera (moths and butterflies) may prove to be an exception to this prediction. Here we report an analysis of sex chromosome dosage compensation in Heliconius butterflies, sampling multiple individuals for several different adult tissues (head, abdomen, leg, mouth, and antennae). Methodologically, we introduce a novel application of linear mixed-effects models to assess dosage compensation, offering a unified statistical framework that can estimate effects specific to chromosome, to sex, and their interactions (i.e., a dosage effect). Our results show substantially reduced Z-linked expression relative to autosomes in both sexes, as previously observed in bombycoid moths. This observation is consistent with an increasing body of evidence that at least some species of moths and butterflies possess an epigenetic sex chromosome dosage compensating mechanism that operates by reducing Z chromosome expression in males. However, this mechanism appears to be imperfect in Heliconius, resulting in a modest dosage effect that produces an average 5-20% male-bias on the Z chromosome, depending on the tissue. Strong sex chromosome dosage effects have been previously in a pyralid moth. Thus our results reflect a mixture of previous patterns reported for Lepidoptera and bisect the emerging view that female-heterogametic ZW taxa have incomplete dosage compensation because they lack a chromosome-wide epigenetic mechanism mediating sex chromosome dosage compensation. In the case of Heliconius, sex chromosome dosage effects persist apparently despite such a mechanism. We also analyze chromosomal distributions of sex-biased genes and show an excess of male-biased and a dearth of female-biased genes on the Z chromosome relative to autosomes, consistent with predictions of sexually antagonistic evolution.

Introgression obscures and reveals historical relationships among the American live oaks

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Introgression obscures and reveals historical relationships among the American live oaks

Deren Eaton , Antonio Gonzalez-Rodriguez , Andrew Hipp , Jeannine Cavender-Bares
doi: http://dx.doi.org/10.1101/016238

Introgressive hybridization challenges the concepts we use to define species and our ability to infer their evolutionary relationships. Methods for inferring historical introgression from the genomes of extant species are now widely used, however, few guidelines have been articulated for how best to interpret their results. Because these tests are inherently comparative, we show that they are sensitivite to the effects of missing data (unsampled species) and to non-independence (hierarchical relationships among species). We demonstrate this using genomic RAD data sampled from populations across the geographic ranges of all extant species in the American live oaks (Quercus series Virentes), a group notorious for hybridization. By considering all species in the clade, and their phylogenetic relationships, we were able to distinguish true hybridizing lineages from those that falsely appear admixed due to phylogenetic structure among hybridizing relatives. Six of seven species show evidence of admixture, often with multiple other species, but which can be explained by hybrid introgression among few related lineages where they occur in close proximity. We identify the Cuban oak as a highly admixed lineage and use an information-theoretic model comparison approach to test alternative scenarios for its origin. Hybrid speciation is a poor fit compared to a model in which a population from Central America colonized Cuba and received subsequent gene flow from Florida. The live oaks form a continuous ring-like distribution around the Gulf of Mexico, connected in Cuba, across which they could effectively exchange alleles. However, introgression appears to remain localized to areas of sympatry, suggesting that oak species boundaries, and their geographic ranges have remained relatively stable over evolutionary time.

Two variance component model improves genetic prediction in family data sets

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Two variance component model improves genetic prediction in family data sets

George Tucker , Po-Ru Loh , Iona M MacLeod , Ben J Hayes , Michael E Goddard , Bonnie Berger , Alkes L Price
doi: http://dx.doi.org/10.1101/016618

Genetic prediction based on either identity by state (IBS) sharing or pedigree information has been investigated extensively using Best Linear Unbiased Prediction (BLUP) methods. However, methods to combine IBS sharing and pedigree information for genetic prediction in humans have not been explored. We introduce a two variance component model for genetic prediction: one component for IBS sharing and one for approximate pedigree structure, both estimated using genetic markers. In simulations using real genotypes from CARe and FHS family cohorts, we demonstrate that the two variance component model achieves gains in prediction r2 over standard BLUP at current sample sizes, and we project based on simulations that these gains will continue to hold at larger sample sizes. Accordingly, in analyses of four quantitative phenotypes from CARe and two quantitative phenotypes from FHS, the two variance component model significantly improves prediction r2 in each case, with up to a 16% relative improvement. We also find that standard mixed model association tests can produce inflated test statistics in datasets with related individuals, whereas the two variance component model corrects for inflation.