Author Archives: cooplab

Author post: Hybrid origins and the earliest stages of diploidization in the highly successful recent polyploid Capsella bursa-pastoris

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This guest post is by Gavin Douglas (@gmdougla), Stephen Wright (@stepheniwright), and Tanja Slotte (@tanjaslotte) on their paper Douglas et al. Hybrid origins and the earliest stages of diploidization in the highly successful recent polyploid Capsella bursa-pastoris. bioRxived here.

photo credit: Tanja Slotte

photo credit: Tanja Slotte


In this preprint we investigate the mode of origin and evolutionary consequences of polyploidy in the highly successful tetraploid plant Capsella bursa-pastoris. We analyze high-coverage massively parallel genomic sequence data and first show that C. bursa-pastoris is a recent hybrid of two Capsella lineages leading to C. grandiflora and C. orientalis. This settles a long-standing uncertainty regarding the origins of C. bursa-pastoris. Second, we investigate patterns of nonfunctionalization and gene loss, and while we find little evidence for rapid, massive genome-wide fractionation, our analyses suggest that there is a decrease in the efficacy of selection in this recently formed tetraploid.

Allopolyploid origins of Capsella bursa-pastoris

Determining the evolutionary origin of C. bursa-pastoris has proven to be difficult and many contradictory hypotheses have been suggested, including that the tetraploid is an autopolyploid of a single Capsella species. Part of the complication has been the relatively low levels of sequence divergence between homeologous gene copies, and across the diploid Capsella lineages. Given population genomic sequences from all three Capsella species mentioned, we were able to address this question again with several different approaches.
C. bursa-pastoris undergoes disomic inheritance, meaning that genes duplicated as a result of polyploidy (homeologs) are independently inherited. Thus, one of the major tasks with our genomic data was to partition out the sequences from the two homeologous subgenomes. Because of the low levels of sequence divergence between homeologs (3% on average), this can be a challenging task. We took two approaches to generate phased genome sequence for inferring species origins; de novo assembly of short reads and phasing of SNPs from mapping reads to the reference genome of the diploid Capsella rubella. Phylogenetic trees generated from de novo assemblies of these species overwhelmingly support one C. bursa-pastoris homeolog forming a clade with C. grandiflora and the other with C. orientalis. The distribution of SNPs and transposable elements shared between these species also strongly support this hybridization model, which we estimate occurred within the last 100-300,000 years.
One reason the hybrid origins of C. bursa-pastoris is exciting is due to the divergent evolution of its progenitor lineages. C. orientalis and C. grandiflora differ both in their mating system and geographical distribution. Given that C. bursa-pastoris is a highly successful weed found worldwide, it will be interesting in future work to assess whether this divergence between the C. orientalis and C. grandiflora lineages contributed to the tetraploid’s adaptability.

Decreased efficacy of selection in the recently arisen polyploid
Following genome duplications the majority of redundant loci are expected to become lost over time through the process of diploidization. This model has been supported by several ancient polyploid events, including in Arabidopsis. Capsella bursa-pastoris presents an interesting model for studying the early phases of diploidization, and allows for an investigation of the rate of gene loss as well as the relative importance of relaxed selection vs. positive selection during early stages of gene inactivation. We searched for large deletions spanning genes using several approaches both based on determination of exact breakpoints and by cross-referencing low-coverage regions in C. bursa-pastoris with other Capsella species. Although we identified proportionately more large deletions segregating in C. bursa-pastoris than in the diploids, we did not find evidence for massive genomic changes in the tetraploid.
We were able to demonstrate relaxation of selection by analyzing the site frequency spectrum of SNPs segregating at 0-fold nonsynonymous sites in the three Capsella species. We also investigated SNPs causing putatively deleterious effects, such as premature stop codons, segregating in the three Capsella. Many of these SNPs are shared between the three species, although segregating at low frequencies in C. grandiflora. Since this shared deleterious variation inherited from progenitors seems to be responsible for a large proportion of the earliest stages of gene degeneration, this data supports a model of genome fractionation that is given a “head start” from standing variation. A key message following from this result is that we should be giving more weight to purely historical explanations of gene loss when studying biased fractionation.

Chromosomal distribution of cyto-nuclear genes in a dioecious plant with sex chromosomes

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Chromosomal distribution of cyto-nuclear genes in a dioecious plant with sex chromosomes
Josh Hough, J Arvid Agren, Spencer CH Barrett, Stephen I Wright

The coordination between nuclear and organellar genes is essential to many aspects of eukaryotic life, including basic metabolism, energy production, and ultimately, organismal fitness. Whereas nuclear genes are bi-parentally inherited, mitochondrial and chloroplast genes are almost exclusively maternally inherited, and this asymmetry may lead to a bias in the chromosomal distribution of nuclear genes whose products act in the mitochondria or chloroplasts. In particular, because X-linked genes have a higher probability of co-transmission with organellar genes (2/3) compared to autosomal genes (1/2), selection for co-adaptation has been predicted to lead to an over-representation of nuclear-mitochondrial (N-mt) or nuclear-chloroplast (N-cp) genes on the X chromosome relative to autosomes. In contrast, the occurrence of sexually antagonistic organellar mutations might lead to selection for movement of cyto-nuclear genes from the X chromosome to autosomes to reduce male mutation load. Recent broad-scale comparative studies of N-mt distributions in animals have found evidence for these hypotheses in some species, but not others. Here, we use transcriptome sequences to conduct the first study of the chromosomal distribution of cyto-nuclear interacting genes in a plant species with sex chromosomes (Rumex hastatulus; Polygonaceae). We found no evidence of under- or over-representation of either N-mt or N-cp genes on the X chromosome, and thus no support for either the co-adaptation or the sexual-conflict hypothesis. We discuss how our results from a species with recently evolved sex chromosomes fit into an emerging picture of the evolutionary forces governing the chromosomal distribution of N-mt and N-cp genes.

Interpretation and approximation tools for big, dense Markov chain transition matrices in ecology and evolution

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Interpretation and approximation tools for big, dense Markov chain transition matrices in ecology and evolution
Katja Reichel, Valentin Bahier, Cédric Midoux, Jean-Pierre Masson, Solenn Stoeckel
Comments: 8 pages, 4 figures, supplement: 2 figures, visual abstract, highlights, source code
Subjects: Quantitative Methods (q-bio.QM); Populations and Evolution (q-bio.PE)

Markov chains are a common framework for individual-based state and time discrete models in ecology and evolution. Their use, however, is largely limited to systems with a low number of states, since the transition matrices involved pose considerable challenges as their size and their density increase. Big, dense transition matrices may easily defy both the computer’s memory and the scientists’ ability to interpret them, due to the very high amount of information they contain; yet approximations using other types of models are not always the best solution.
We propose a set of methods to overcome the difficulties associated with big, dense Markov chain transition matrices. Using a population genetic model as an example, we demonstrate how big matrices can be transformed into clear and easily interpretable graphs with the help of network analysis. Moreover, we describe an algorithm to save computer memory by substituting the original matrix with a sparse approximate while preserving all its mathematically important properties. In the same model example, we manage to store about 90% less data while keeping more than 99% of the information contained in the matrix and a closely corresponding dominant eigenvector.
Our approach is an example how numerical limitations for the number of states in a Markov chain can be overcome. By facilitating the use of state-rich Markov chain models, they may become a valuable supplement to the diversity of models currently employed in biology.

The site frequency spectrum of dispensable genes

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The site frequency spectrum of dispensable genes
Franz Baumdicker
Comments: 24 pages, 8 figures
Subjects: Populations and Evolution (q-bio.PE); Probability (math.PR)

The differences between DNA-sequences within a population are the basis to infer the ancestral relationship of the individuals. Within the classical infinitely many sites model, it is possible to estimate the mutation rate based on the site frequency spectrum, which is comprised by the numbers $C_1,…,C_{n-1}$, where n is the sample size and $C_s$ is the number of site mutations (Single Nucleotide Polymorphisms, SNPs) which are seen in $s$ genomes. Classical results can be used to compare the observed site frequency spectrum with its neutral expectation, $E[C_s]= \theta_2/s$, where $\theta_2$ is the scaled site mutation rate. In this paper, we will relax the assumption of the infinitely many sites model that all individuals only carry homologous genetic material. Especially, it is today well-known that bacterial genomes have the ability to gain and lose genes, such that every single genome is a mosaic of genes, and genes are present and absent in a random fashion, giving rise to the dispensable genome. While this presence and absence has been modeled under neutral evolution within the infinitely many genes model in previous papers, we link presence and absence of genes with the numbers of site mutations seen within each gene. In this work we derive a formula for the expectation of the joint gene and site frequency spectrum, denotes $G_{k,s}$ the number of mutated sites occurring in exactly $s$ gene sequences, while the corresponding gene is present in exactly $k$ individuals. We show that standard estimators of $\theta_2$ for dispensable genes are biased and that the site frequency spectrum for dispensable genes differs from the classical result.

Extraordinarily wide genomic impact of a selective sweep associated with the evolution of sex ratio distorter suppression

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Extraordinarily wide genomic impact of a selective sweep associated with the evolution of sex ratio distorter suppression
Emily A Hornett, Bruce Moran, Louise A Reynolds, Sylvain Charlat, Samuel Tazzyman, Nina Wedell, Chris D Jiggins, Gregory Hurst

Symbionts that distort their host?s sex ratio by favouring the production and survival of females are common in arthropods. Their presence produces intense Fisherian selection to return the sex ratio to parity, typified by the rapid spread of host ?suppressor? loci that restore male survival/development. In this study, we investigated the genomic impact of a selective event of this kind in the butterfly Hypolimnas bolina. Through linkage mapping we first identified a genomic region that was necessary for males to survive Wolbachia-induced killing. We then investigated the genomic impact of the rapid spread of suppression that converted the Samoan population of this butterfly from a 100:1 female-biased sex ratio in 2001, to a 1:1 sex ratio by 2006. Models of this process revealed the potential for a chromosome-wide selective sweep. To measure the impact directly, the pattern of genetic variation before and after the episode of selection was compared. Significant changes in allele frequencies were observed over a 25cM region surrounding the suppressor locus, alongside generation of linkage disequilibrium. The presence of novel allelic variants in 2006 suggests that the suppressor was introduced via immigration rather than through de novo mutation. In addition, further sampling in 2010 indicated that many of the introduced variants were lost or had reduced in frequency since 2006. We hypothesise that this loss may have resulted from a period of purifying selection – removing deleterious material that introgressed during the initial sweep. Our observations of the impact of suppression of sex ratio distorting activity reveal an extraordinarily wide genomic imprint, reflecting its status as one of the strongest selective forces in nature.

inPHAP: Interactive visualization of genotype and phased haplotype data

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inPHAP: Interactive visualization of genotype and phased haplotype data
Günter Jäger, Alexander Peltzer, Kay Nieselt
Comments: BioVis 2014 conference
Subjects: Graphics (cs.GR); Genomics (q-bio.GN)

Background: To understand individual genomes it is necessary to look at the variations that lead to changes in phenotype and possibly to disease. However, genotype information alone is often not sufficient and additional knowledge regarding the phase of the variation is needed to make correct interpretations. Interactive visualizations, that allow the user to explore the data in various ways, can be of great assistance in the process of making well informed decisions. But, currently there is a lack for visualizations that are able to deal with phased haplotype data. Results: We present inPHAP, an interactive visualization tool for genotype and phased haplotype data. inPHAP features a variety of interaction possibilities such as zooming, sorting, filtering and aggregation of rows in order to explore patterns hidden in large genetic data sets. As a proof of concept, we apply inPHAP to the phased haplotype data set of Phase 1 of the 1000 Genomes Project. Thereby, inPHAP’s ability to show genetic variations on the population as well as on the individuals level is demonstrated for several disease related loci. Conclusions: As of today, inPHAP is the only visual analytical tool that allows the user to explore unphased and phased haplotype data interactively. Due to its highly scalable design, inPHAP can be applied to large datasets with up to 100 GB of data, enabling users to visualize even large scale input data. inPHAP closes the gap between common visualization tools for unphased genotype data and introduces several new features, such as the visualization of phased data.

V genes in primates from whole genome shotgun data

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V genes in primates from whole genome shotgun data
David N Olivieri, Francisco Gambon-Deza

The adaptive immune system uses V genes for antigen recognition. The evolutionary diversification and selection processes within and across species and orders are poorly understood. Here, we studied the amino acid (AA) sequences obtained of translated in-frame V exons of immunoglobulins (IG) and T cell receptors (TR) from 16 primate species whose genomes have been sequenced. Multi-species comparative analysis supports the hypothesis that V genes in the IG loci undergo birth/death processes, thereby permitting rapid adaptability over evolutionary time. We also show that multiple cladistic groupings exist in the TRA (35 clades) and TRB (25 clades) V gene loci and that each primate species typically contributes at least one V gene to each of these clade. The results demonstrate that IG V genes and TR V genes have quite different evolutionary pathways; multiple duplications can explain the IG loci results, while co-evolutionary pressures can explain the phylogenetic results, as seen in genes of the TR loci. We describe how each of the 35 V genes clades of the TRA locus and 25 clades of the TRB locus must have specific and necessary roles for the viability of the species.

Improved genome inference in the MHC using a population reference graph

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Improved genome inference in the MHC using a population reference graph
Alexander Dilthey, Charles J Cox, Zamin Iqbal, Matthew R Nelson, Gil McVean

In humans and many other species, while much is known about the extent and structure of genetic variation, such information is typically not used in assembling novel genomes. Rather, a single reference is used against which to map reads, which can lead to poor characterisation of regions of high sequence or structural diversity. Here, we introduce a population reference graph, which combines multiple reference sequences as well as catalogues of SNPs and short indels. The genomes of novel samples are reconstructed as paths through the graph using an efficient hidden Markov Model, allowing for recombination between different haplotypes and variants. By applying the method to the 4.5Mb extended MHC region on chromosome 6, combining eight assembled haplotypes, sequences of known classical HLA alleles and 87,640 SNP variants from the 1000 Genomes Project, we demonstrate, using simulations, SNP genotyping, short-read and long-read data, how the method improves the accuracy of genome inference. Moreover, the analysis reveals regions where the current set of reference sequences is substantially incomplete, particularly within the Class II region, indicating the need for continued development of reference-quality genome sequences.

Convergent Evolution During Local Adaptation to Patchy Landscapes

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Convergent Evolution During Local Adaptation to Patchy Landscapes
Peter L. Ralph, Graham Coop

Species often encounter, and adapt to, many patches of locally similar environmental conditions across their range. Such adaptation can occur through convergent evolution as different alleles arise and spread in different patches, or through the spread of alleles by migration acting to synchronize adaptation across the species. The tension between the two reflects the degree of constraint imposed on evolution by the underlying genetic architecture versus how how effectively selection acts to inhibit the geographic spread of locally adapted alleles. This paper studies a model of the balance between these two routes to adaptation in continuous environments with patchy selection pressures. We address the following questions: How long does it take for a new, locally adapted allele to appear in a patch of habitat where it is favored through new mutation? Or, through migration from another, already adapted patch? Which is more likely to occur, as a function of distance between the patches? How can we tell which has occurred, i.e.\ what population genetic signal is left by the spread of migrant alleles and how long does this signal persist for? To answer these questions we decompose the migration–selection equilibrium surrounding an already adapted patch into families of migrant alleles, in particular treating those rare families that reach new patches as spatial branching processes. This provides a way to understand the role of geographic separation between patches in promoting convergent adaptation and the genomic signals it leaves behind. We illustrate these ideas using the convergent evolution of cryptic coloration in the rock pocket mouse, Chaetodipus intermedius, as an empirical example.

Purifying selection, drift and reversible mutation with arbitrarily high mutation rates

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Purifying selection, drift and reversible mutation with arbitrarily high mutation rates
Brian Charlesworth, Kavita Jain
Comments: Supplementary Information available on request
Subjects: Populations and Evolution (q-bio.PE)

Some species exhibit very high levels of DNA sequence variability; there is also evidence for the existence of heritable epigenetic variants that experience state changes at a much higher rate than sequence variants. In both cases, the resulting high diversity levels within a population (hyperdiversity) mean that standard population genetics methods are not trustworthy. We analyze a population genetics model that incorporates purifying selection, reversible mutations and genetic drift, assuming a stationary population size. We derive analytical results for both population parameters and sample statistics, and discuss their implications for studies of natural genetic and epigenetic variation. In particular, we find that (1) many more intermediate frequency variants are expected than under standard models, even with moderately strong purifying selection (2) rates of evolution under purifying selection may be close to, or even exceed, neutral rates. These findings are related to empirical studies of sequence and epigenetic variation.