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Zurich Colloquium for Computational Molecular Evolution (ZC-CME 2013)

One of the fundamental concepts behind Darwin's theory of evolution is “descent with modification”. From a common ancestor, populations and species diverge during the course of evolution, where natural selection is the main driving force. This process is traditionally envisioned through a phylogenetic tree. Since Darwin's ideas were published in his Origin of Species, statisticians, mathematicians, computer scientists, biologists, chemists and physicists have joined their forces developing both methodological and experimental aspects of the field.


Scope

The focus of this seminar series is on statistical and computational methodology to study how genomes of organisms evolve, the driving forces of change at both phenotypic and molecular levels. We aim to encourage and promote the innovation in statistical and computational approaches, and the interdisciplinary character of the field.

Organizers

Maria Anisimova

Please contact me if you would like to join the mailing list for this colloquium.

Funding

This seminar is jointly funded by the CBRG and the SIB.

Program

This is a preliminary program. It is still subject to change since we do not have confirmation from all speakers yet. Only the dates in bold have already been confirmed.

Date
Time/Room
Speaker and Title
Thur,
24 Jan 2013
11:15

CAB H 52

Maxim Kapralov
Department of Plant Sciences, University of Oxford, UK

Adaptive evolution of the key photosynthetic enzyme, Rubisco

Tue, 26 Feb 2013 14:15

CAB H 52

Tugce Bilgin
Institute of Evolutionary Biology and Environmental Sciences, UZH
Tandem repeats in promoters enhance expression divergence in primates

Thur, 25 April 2013 14:15

CHN D 46

Ivo Pedruzzi

Swiss-Pro, Swiss Institue of Bioinformatics, Geneva

Bringing Swiss-Prot quality annotations to TrEMBL: New developments in HAMAP, the protein family classification and annotation system for UniProtKB

Tue, 21 May 2013
14:15

CHN F 42

Toni Gabaldon

Center for Genomic Regulation, Barcelona, Spain

Phylogenomics in the light of ever-growing sequencing data

Mon, 2 Sept 2013
10:15

CAB H 52

Julien Dutheil

Max Planck Institute for Terrestrial Microbiology
Marburg, Germany AND Institut des Sciences de l'Évolution, Université de Montpellier II, France

Recurrent selective sweeps explain low divergence of the Human X chromosome

Mon, 23 Sept 2013
14:15

CAB H 52

Jun Sese

Tokyo Institute of Technology, Japan

On statistical significance for untangling complex genotype-phenotype connections

Tue, 17 Dec 2013 15:15

LFW E 15

(followed by an apero at 16:15)

David Posada

University of Vigo, Spain

Phylogenomic estimation of species trees

Previous years

The list of speakers/abstracts for previous years are available here: 2012, 2011, 2010, 2009, 2008, 2007.

Abstracts

Adaptive evolution of the key photosynthetic enzyme Rubisco

Maxim Kapralov

Department of Plant Sciences, University of Oxford, UK

Ribulose-1,5-bisphospate carboxylase/oxygenase, called for short Rubisco, serves as a gateway for inorganic carbon to enter metabolic pathways in most ecosystems on Earth. Rubisco is literally the most abundant enzyme in the world and comprises up to 50% of all soluble protein in photosynthetic tissues, which is the price that plants have to pay for its large size and very slow turnover. As the performance of Rubisco can greatly affect crop yields, substantial efforts have been made to study its structure and function using directed mutagenesis, with the aim to artificially improve Rubisco performance. However, neither the practical problem of delivering better enzymes for crops nor the fundamental questions about Rubisco evolution in different groups of plants have been resolved so far. We showed how Rubisco is adapting to changing environment in short and long term via changes in gene expression and amino acid replacements, respectively. Positive selection on the level of nucleotides and amino acids as well as co-evolution of residues are common during Rubisco evolution and will be discussed. Our results suggest that Rubisco properties are being adjusted by natural selection to better fit the environmental conditions and that currently predominant “one size fits all” model for Rubisco kinetics is incorrect.

Tandem repeats in promoters enhance expression divergence in primates

Tugce Bilgin

Institute of Evolutionary Biology and Environmental Sciences, University of Zurich

Tandem repeats in eukaryotic gene promoters can change gene expression drastically due to their extremely low stability. We hypothesized that unstable tandem repeats in promoters increase expression divergence along the primate phylogeny. A search for tandem repeats in promoter regions of 13,000 human, chimpanzee and macaque orthologous genes revealed that 30 % of primate promoters contain tandem repeats. Genes driven by these repeat-containing promoters show significantly higher rates of expression divergence. More specifically, we found a significant correlation between repeat instability and expression divergence. This relation might explain gene expression divergence in more special cases, as in gene duplication events or in disease formation.

Bringing Swiss-Prot quality annotations to TrEMBL: New developments in HAMAP, the protein family classification and annotation system for UniProtKB

Ivo Pedruzzi

Swiss-Pro, Swiss Institue of Bioinformatics, Geneva

HAMAP (High-quality Automated and Manual Annotation of Proteins) is a system for the classification and annotation of protein sequences. It consists of a collection of manually curated family profiles for protein classification, and associated annotation rules that specify annotations that apply to family members. HAMAP was originally developed to support the manual curation of UniProtKB/Swiss-Prot records describing microbial proteins. New developments in HAMAP include the extension of HAMAP to eukaryotic proteins and the use of HAMAP in the automated annotation of UniProtKB/TrEMBL, providing high quality annotation for millions of protein sequences. HAMAP is continuously updated by expert curators with new family profiles and annotation rules as new protein families are characterized, and rules are applied anew with each UniProtKB release, keeping the propagated annotation up-to-date. The collection of HAMAP family classification profiles and annotation rules can be accessed on the HAMAP website (http://hamap.expasy.org) and can be used directly for the annotation of protein sequences via our web interface. Users may submit individual protein sequences or complete microbial proteomes to be scanned against the entire collection of HAMAP profiles and annotated by HAMAP rules.

Phylogenomics in the light of ever-growing sequencing data

Toni Gabaldon

Comparative Genomics Group, Bioinformatics and Genomic Programme, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain

A pressing challenge in phylogenomics is the need to cope with the massive production of complete genomic sequences, especially after recent technological developments. Problems that are particularly affected by the increasing flow of genomic data and that require continuous update are: i) the establishment of evolutionary relationships between species (the so-called Tree Of Life (TOL)), ii) the inference of orthology and paralogy relationships across genomes, and iii) the study of the evolution of large, widespread super-families that evolved through complex patterns of duplications and losses. To face such challenges we have developed two sophisticated pipelines that allow high scalability and continuous update, while achieving highest levels of accuracy. The first such pipeline automatically reconstructs entire species-centric collections of gene phylogenies (the so-called phylome), and combines this with phylogenetic information from various other sources to derive unique orthology and paralogy predictions. The second pipeline, which we apply to the superfamily and the Tree of Life assembly problems, is able to reconstruct large phylogenies by means of an iterative strategy that provides scalable resolution and allows continuous update. In this talk, I will illustrate the use of such approaches in the context of the assessment of the evolution of important traits in fungi, and the reconstruction of a genome-based, eukaryotic tree of life.

Recurrent selective sweeps explain low divergence of the Human X chromosome

Julien Y. Dutheil

Max Planck Institute for Terrestrial Microbiology Marburg, Germany AND Institut des Sciences de l'Évolution, Université de Montpellier II, France

Genomic patterns of human and chimp divergence of have led to controversial hypotheses on the underlying speciation mechanisms. It was previously observed that divergence of the X chromosome is extremely reduced relative to the one of autosomes,  which cannot be explained by a simple speciation model without invoking strong mutational biases. We analyzed a full X chromosome alignment of human, chimp, gorilla and orangutan. We found that patterns of incomplete lineage sorting (ILS) along the X chromosome are compatible with a simple instantaneous speciation model with panmictic ancestral population. Conversely, a few large regions of the chromosome alignment show a drastically reduced divergence and amount of ILS. We propose that such regions are responsible for previous reports of a globally reduced divergence of the full X chromosome. We argue that recurrent and independent selective sweeps must have occurred in these regions to generate this pattern.

On statistical significance for untangling complex genotype-phenotype connections

Jun Sese

Dept. of Computer Science, Tokyo Institute of Technology, Japan

To understand complex associations between genotypes and phenotypes, the first analysis step is to list up statistically significant combinations of the features. However, the discovery is not only computationally non-trivial but also extremely unlikely due to multiple testing correction. The exponential growth of the number of tests forces us to set a strict limit to the maximum arity. In this talk, we introduce an efficient branch-and-bound algorithm named Limitless Arity Multiple testing Procedure (LAMP) to count the exact number of testable combinations and calibrate the Bonferroni factor to the smallest possible value. LAMP lists up significant combinations without any limit, while the family-wise error rate is rigorously controlled under the threshold. We applied LAMP to the discovery of combinatorial regulations of transcription factors. From human breast cancer transcriptome, LAMP discovered statistically significant combinations of as many as eight binding motifs. This method may contribute to uncover pathways regulated in a coordinated fashion and find hidden associations in GWAS data.

Reference: Statistical Significance of Combinatorial Regulations. Terada et al. 2013. PNAS.
Web: http://seselab.org/lamp/


Phylogenomic estimation of species trees

David Posada

Biology department, University of Vigo, Spain

The unprecedented amount of data resulting from NGS techniques has opened a new era in phylogenomics. However, although large datasets should in theory increase resolution, multilocus data has also uncovered a great deal of phylogenetic incongruence among different genomic regions, due both to stochastic error and to the action of different evolutionary process like incomplete lineage sorting, gene duplication and loss and horizontal gene transfer. In this talk I will explain some of the most important challenges we will have to face to reconstruct the history of species. I will describe a new phylogenomic species tree approach that we have recently developed in order to find a good trade-off between model complexity and computational feasibility. In addition, I will discuss the implications of incomplete lineage sorting when assessing orthology and paralogy in gene families.


 

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