Author Archives: cooplab

The first steps of adaptation of Escherichia coli to the gut are dominated by soft sweeps

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The first steps of adaptation of Escherichia coli to the gut are dominated by soft sweeps
João Barroso-Batista, Ana Sousa, Marta Lourenço, Marie-Louise Bergman, Jocelyne Demengeot, Karina B. Xavier, Isabel Gordo
(Submitted on 11 Nov 2013)

The accumulation of adaptive mutations is essential for survival in novel environments. However, in clonal populations with a high mutational supply, the power of natural selection is expected to be limited. This is due to clonal interference – the competition of clones carrying different beneficial mutations – which leads to the loss of many small effect mutations and fixation of large effect ones. If interference is abundant, then mechanisms for horizontal transfer of genes, which allow the immediate combination of beneficial alleles in a single background, are expected to evolve. However, the relevance of interference in natural complex environments, such as the gut, is poorly known. To address this issue, we studied the invasion of beneficial mutations responsible for Escherichia coli’s adaptation to the mouse gut and demonstrate the pervasiveness of clonal interference. The observed dynamics of change in frequency of beneficial mutations are consistent with soft sweeps, where a similar adaptive mutation arises repeatedly on different haplotypes without reaching fixation. The genetic basis of the adaptive mutations revealed a striking parallelism in independently evolving populations. This was mainly characterized by the insertion of transposable elements in both coding and regulatory regions of a few genes. Interestingly in most populations, we observed a complete phenotypic sweep without loss of genetic variation. The intense clonal interference during adaptation to the gut environment, here demonstrated, may be important for our understanding of the levels of strain diversity of E. coli inhabiting the human gut microbiota and of its recombination rate.

A stochastic microscopic model for the dynamics of antigenic variation

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A stochastic microscopic model for the dynamics of antigenic variation
Gustavo Guerberoff, Fernando Alvarez-Valin
(Submitted on 8 Nov 2013)

We present a novel model that describes the within-host evolutionary dynamics of parasites undergoing antigenic variation. The approach uses a multi-type branching process with two types of entities defined according to their relationship with the immune system: clans of resistant parasitic cells (i.e. groups of cells sharing the same antigen not yet recognized by the immune system) that may become sensitive, and individual sensitive cells that can acquire a new resistance thus giving rise to the emergence of a new clan. The simplicity of the model allows analytical treatment to determine the subcritical and supercritical regimes in the space of parameters. By incorporating a density-dependent mechanism the model is able to capture additional relevant features observed in experimental data, such as the characteristic parasitemia waves. In summary our approach provides a new general framework to address the dynamics of antigenic variation which can be easily adapted to cope with broader and more complex situations.

Mapping of the Influenza-A Hemagglutinin Serotypes Evolution by the ISSCOR Method

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Mapping of the Influenza-A Hemagglutinin Serotypes Evolution by the ISSCOR Method
Jan P. Radomski, Piotr P. Slonimski, Włodzimierz Zagórski-Ostoja, Piotr Borowicz
(Submitted on 8 Nov 2013)

Analyses and visualizations by the ISSCOR method of influenza virus hemagglutinin genes of different A-subtypes revealed some rather striking temporal relationships between groups of individual gene subsets. Based on these findings we consider application of the ISSCOR-PCA method for analyses of large sets of homologous genes to be a worthwhile addition to a toolbox of genomics – allowing for a rapid diagnostics of trends, and ultimately even aiding an early warning of newly emerging epidemiological threats.

Sequencing and characterisation of rearrangements in three S. pastorianus strains reveals the presence of chimeric genes and gives evidence of breakpoint reuse

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Sequencing and characterisation of rearrangements in three S. pastorianus strains reveals the presence of chimeric genes and gives evidence of breakpoint reuse
Sarah K. Hewitt, Ian Donaldson, Simon C. Lovell, Daniela Delneri
(Submitted on 8 Nov 2013)

Gross chromosomal rearrangements have the potential to be evolutionarily advantageous to an adapting organism. The generation of a hybrid species increases opportunity for recombination by bringing together two homologous genomes. We sought to define the location of genomic rearrangements in three strains of Saccharomyces pastorianus, a natural lager-brewing yeast hybrid of Saccharomyces cerevisiae and Saccharomyces eubayanus, using whole genome shotgun sequencing. Each strain of S. pastorianus has lost species-specific portions of its genome and has undergone extensive recombination, producing chimeric chromosomes. We predicted 30 breakpoints that we confirmed at the single nucleotide level by designing species-specific primers that flank each breakpoint, and then sequencing the PCR product. These rearrangements are the result of recombination between areas of homology between the two subgenomes, rather than repetitive elements such as transposons or tRNAs. Interestingly, 28/30 S. cerevisiae- S. eubayanus recombination breakpoints are located within genic regions, generating chimeric genes. Furthermore we show evidence for the reuse of two breakpoints, located in HSP82 and KEM1, in strains of proposed independent origin.

The hemagglutinin mutation E391K of pandemic 2009 influenza revisited

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The hemagglutinin mutation E391K of pandemic 2009 influenza revisited
Jan P. Radomski, Piotr Płoński, Włodzimierz Zagórski-Ostoja
(Submitted on 8 Nov 2013)

Phylogenetic analyses based on small to moderately sized sets of sequential data lead to overestimating mutation rates in influenza hemagglutinin (HA) by at least an order of magnitude. Two major underlying reasons are: the incomplete lineage sorting, and a possible absence in the analyzed sequences set some of key missing ancestors. Additionally, during neighbor joining tree reconstruction each mutation is considered equally important, regardless of its nature. Here we have implemented a heuristic method optimizing site dependent factors weighting differently 1st, 2nd, and 3rd codon position mutations, allowing to extricate incorrectly attributed sub-clades. The least squares regression analysis of distribution of frequencies for all mutations observed on a partially disentangled tree for a large set of unique 3243 HA sequences, along all nucleotide positions, was performed for all mutations as well as for non-equivalent amino acid mutations: in both cases demonstrating almost flat gradients, with a very slight downward slope towards the 3′-end positions. The mean mutation rates per sequence per year were 3.83*10^-4 for the all mutations, and 9.64*10^-5 for the non-equivalent ones.

Comparative Assembly Hubs: Web Accessible Browsers for Comparative Genomics

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Comparative Assembly Hubs: Web Accessible Browsers for Comparative Genomics
Ngan Nguyen, Glenn Hickey, Brian J. Raney, Joel Armstrong, Hiram Clawson, Ann Zweig, Jim Kent, David Haussler, Benedict Paten
(Submitted on 5 Nov 2013)

We introduce a pipeline to easily generate collections of web accessible UCSC genome browsers interrelated by an alignment. Using the alignment, all annotations and the alignment itself can be efficiently viewed with reference to any genome in the collection, symmetrically. A new, intelligently scaled alignment display makes it simple to view all changes between the genomes at all levels of resolution, from substitutions to complex structural rearrangements, including duplications.

The inference of gene trees with species trees

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The inference of gene trees with species trees
Gergely J. Szöllosi, Eric Tannier, Vincent Daubin, Bastien Boussau
(Submitted on 4 Nov 2013)

Molecular phylogeny has focused mainly on improving models for the reconstruction of gene trees based on sequence alignments. Yet, most phylogeneticists seek to reveal the history of species. Although the histories of genes and species are tightly linked, they are seldom identical, because genes duplicate, are lost or horizontally transferred, and because alleles can co-exist in populations for periods that may span several speciation events. Building models describing the relationship between gene and species trees can thus improve the reconstruction of gene trees when a species tree is known, and vice-versa. Several approaches have been proposed to solve the problem in one direction or the other, but in general neither gene trees nor species trees are known. Only a few studies have attempted to jointly infer gene trees and species trees. In this article we review the various models that have been used to describe the relationship between gene trees and species trees. These models account for gene duplication and loss, transfer or incomplete lineage sorting. Some of them consider several types of events together, but none exists currently that considers the full repertoire of processes that generate gene trees along the species tree. Simulations as well as empirical studies on genomic data show that combining gene tree-species tree models with models of sequence evolution improves gene tree reconstruction. In turn, these better gene trees provide a better basis for studying genome evolution or reconstructing ancestral chromosomes and ancestral gene sequences. We predict that gene tree-species tree methods that can deal with genomic data sets will be instrumental to advancing our understanding of genomic evolution.

An HMM-based Comparative Genomic Framework for Detecting Introgression in Eukaryotes

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An HMM-based Comparative Genomic Framework for Detecting Introgression in Eukaryotes
Kevin J. Liu, Jingxuan Dai, Kathy Truong, Ying Song, Michael H. Kohn, Luay Nakhleh
(Submitted on 30 Oct 2013)

One outcome of interspecific hybridization and subsequent effects of evolutionary forces is introgression, which is the integration of genetic material from one species into the genome of an individual in another species. The evolution of several groups of eukaryotic species has involved hybridization, and cases of adaptation through introgression have been already established. In this work, we report on a new comparative genomic framework for detecting introgression in genomes, called PhyloNet-HMM, which combines phylogenetic networks, that capture reticulate evolutionary relationships among genomes, with hidden Markov models (HMMs), that capture dependencies within genomes. A novel aspect of our work is that it also accounts for incomplete lineage sorting and dependence across loci.
Application of our model to variation data from chromosome 7 in the mouse (Mus musculus domesticus) genome detects a recently reported adaptive introgression event involving the rodent poison resistance gene Vkorc1, in addition to other newly detected introgression regions. Based on our analysis, it is estimated that about 12% of all sites withinchromosome 7 are of introgressive origin (these cover about 18 Mbp of chromosome 7, and over 300 genes). Further, our model detects no introgression in two negative control data sets. Our work provides a powerful framework for systematic analysis of introgression while simultaneously accounting for dependence across sites, point mutations, recombination, and ancestral polymorphism.

Global patterns of sex-biased migrations in humans

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Global patterns of sex-biased migrations in humans
Chuan-Chao Wang, Li Jin, Hui Li
(Submitted on 29 Oct 2013)

A series of studies have revealed the among-population components of genetic variation are higher for the paternal Y chromosome than for the maternal mitochondrial DNA (mtDNA), which indicates sex-biased migrations in human populations. However, this phenomenon might be also an ascertainment bias due to nonrandom sampling of SNPs. To eliminate the possible bias, we used the whole Y chromosome and mtDNA sequence data of 491 individuals from the 1000 Genomes Project Phase I to address the sex-biased migration dispute. We found that genetic differentiation between populations was higher for Y chromosome than for the mtDNA at global scales. The migration rate of female might be three times higher than that of male, assuming the effective population size is the same for male and female.

Can we predict the mutation rate at the single nucleotide scale in the human genome?

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Can we predict the mutation rate at the single nucleotide scale in the human genome?
Adam Eyre-Walker, Ying Chen
(Submitted on 29 Oct 2013)

It has been recently claimed that it is possible to predict the rate of de novo mutation of each site in the human genome with almost perfect accuracy (Michaelson et al. (2012) Cell, 151, 1431-1442). We show that this claim is unwarranted. By considering the correlation between the rate of de novo mutation and the predictions from the model of Michaelson et al., we show that there could be substantial unexplained variance in the mutation rate. We also demonstrate that the model of Michaelson et al. fails to capture a major component of the variation in the mutation rate, that which is local but not associated with simple context.