[BC]2 Basel Computational Biology Conference 2009 - Molecular Evolution

7^th [BC]² Basel Computational Biology Conference

"Molecular Evolution"

Messe Basel

June 18 & 19, 2009

Abstracts

Evolution of Eyes and Photoreceptors

Walter J. Gehring (Biozentrum University of Basel, Switzerland)

Recent experiments on the genetic control of eye development have opened up a completely new perspective on eye evolution. The demonstration that targeted expression of one and the same master control gene, that is, Pax6 can induce the formation of ectopic eyes in both insects and vertebrates, necessitates a reconsideration of the dogma of a polyphyletic origin of the various eye types in all the animal phyla. The involvement of Pax6 and six1 and six3 genes, which encode highly conserved transcription factors, in the genetic control of eye development in organisms ranging from planarians to humans argues strongly for a monophyletic origin of the eye. Because transcription factors can control the expression of any target gene provided it contains the appropriate gene regulatory elements, the conservation of the genetic control of eye development by Pax6 among all bilaterian animals is not due to functional constraints, but a consequence of its evolutionary history.

Population genetics and genomics of human gene expression

Emmanouil T. Dermitzakis (University of Geneva, Switzerland)

The recent comparative analysis of the human genome has revealed a large fraction of functionally constrained non-coding DNA in mammalian genomes. However, our understanding of the function of non-coding DNA is very limited. In this talk I will present recent analysis in my group and collaborators that aims at the identification of functionally variable regulatory regions in the human genome by correlating SNPs and copy number variants with gene expression data. In the particular talk I will present analysis of gene expression data from 850 individuals from 8 diverse human populations from the hapmap3 project. Issues of population differentiation and natural selection will be discussed. I will also present our recent analysis on RNAseq data from the 60 CEU individuals from the 1000 genomes project.

Natural selection against protein misfolding

D. Allan Drummond (Harvard University)

The rate at which substitutions accumulate in coding sequences is a fundamental measure of evolutionary change at the molecular level, yet the causes of evolutionary rate variation remain controversial. While it is commonly assumed that functionally important genes evolve slowly, most variation in evolutionary rates remains even when considering only essential genes. We have proposed that selection acts to reduce the proportion of protein molecules which misfold after synthesis (the misfolding hypothesis). In support of this hypothesis, we present integrated evidence from genome sequence evolution and codon usage, functional genomics, translation profiling, global and tissue-specific gene expression across multiple organisms, and large-scale simulation studies. Using quantitative Western blotting, we probe duplicated genes in the yeast Saccharomyces cerevisiae which have similar structure and function but different mRNA levels, such as pyruvate kinases 1 and 2. We show that, as predicted, the highly expressed gene produces less misfolded protein than its weakly expressed paralog. We discuss the relative contributions to rates of protein evolution from selection on function and selection to reduce costs of synthesis, maintenance, and degradation.

Evolution during range expansions

Laurent Excoffier (SIB & University of Bern, Switzerland)

While range expansions have occurred recurrently in the history of most species, their genetic consequences have been little investigated. Theoretical studies have shown that range expansions are quite different from pure demographic expansions and that the extent of recent gene flow conditions expected patterns of molecular diversity within and between populations. Spatially explicit simulation studies have led to unexpected and fascinating results about genetic patterns emerging after a range expansion. For instance, spatial expansions can generate allele frequency gradients, promote the surfing of rare variants into newly occupied territories, induce the structuring of newly colonized areas into distinct sectors of low genetic diversity, or lead to massive introgression of local genes into the genome of an invading species. Interestingly, most of these patterns had been previously attributed to distinct selective processes, showing that taking into account the dynamic nature of a species range can lead to a paradigm shift in our perception of evolutionary processes.

Darwin's Garden

Francois Felber (University of Neuchatel, Switzerland)

Following his five years travel around the world, Charles Darwin (1809-1882) settled for several decades at Down House in England. He elaborated his theory on evolution and made also significant contributions to other fields of biology. The botanical work of Darwin in the fields of domestication, pollination biology of plants including orchids, biology of insectivore plants and movements of climbing plants will be overviewed.

The Genomic rate of Adaptive Evolution

Adam Eyre-Walker (University of Sussex)

The relative roles of advantageous and neutral mutations in the evolutionary process has been one of the central problems in molecular evolution for over 40 years. I will describe work that we and others have been doing over the few years to answer this question with respect to protein coding sequences. While Drosophila, enteric bacteria and mice show very high levels of adaptive evolution, with >50% of amino acid substitutions being estimated to be a consequence of positive selection, humans and plants show almost no evidence of widespread adaptive evolution. The reasons for these differences will be discussed.

Universals of genomic and phenomic evolution

Eugene V. Koonin (National Center for Biotechnology Information, NLM, NIH)

Comparative genomics and systems biology reveal several surprising universals of genomic and phenomic evolution such as the distribution of evolution rates across genes, the distribution of paralogous gene family size, and connections between expression and evolution rate. The existence of these universals calls for simple, general models of evolutionary processes akin to those used in statistical physics (e.g., birth and death processes), and at least in some cases, such models seem to explain the observed universal patterns. These general evolutionary models do not explicitly include selection suggesting that the basic processes underlying evolution are non-adaptive. Therefore, it seems to make sense to seek a non-adaptive null model for any evolutionary process or phenomenon before invoking adaptation. Where evidence of selection is seen, the subject of selection is often not a specific function of gene/protein but rather robustness to malfunction or, more generally, maintenance of the basic organization of genome/cell. The quest for simple, even law-like regularities underlying evolution might not be futile: comparative genomics and evolutionary systems biology are starting to uncover such patterns. The applicability of simple models to the basic processes of evolution does not contradict the "evolution as tinkering" metaphor of Francois Jacob: the specific outcomes of these regular processes involve a strong element of contingency, and are modulated by adaptive tinkering. In general terms, evolutionary biology is not dramatically different from physics/astrophysics/cosmology: the basic processes obey law-like patterns but the specific outcomes are determined by chance conditioned by adaptation, and are unpredictable - within the applicable constraints.

Dynamics of Phenotypic and Genomic Evolution During a 40,000-Generation Experiment with E. coli

Richard E. Lenski (Department of Microbiology and Molecular Genetics, Michigan State University)

Twelve initially identical populations of E. coli have been propagated in a simple, defined laboratory environment since 1988. The two overarching goals of this experiment have been to examine the reproducibility of evolutionary outcomes, and to investigate the dynamics of phenotypic and genomic evolution. We have quantified adaptation by natural selection [1], documented increasing ecological specialization over time [2], observed the rise of mutator phenotypes [3], and even seen the origin of a new function that transcends the usual definition of E. coli as a species [4]. We have pursued several genetic approaches, from tracking mobile elements [5] to examining changes in gene-expression profiles [6], to discover the mutations responsible for these changes, including several affecting global regulatory networks [6-8]. We have also recently sequenced many complete genomes in order to find all of the mutations present in temporal series of clones sampled from some populations. These genomic data are providing new insights into the dynamical coupling of phenotypic and genomic evolution, and into the role of complex mutations in the origin of new functions.

Lenski RE, Travisano M (1994) Dynamics of adaptation and diversification: a 10,000-generation experiment with bacterial populations. PNAS 91:6808-6814.
Cooper VS, Lenski RE (2000) The population genetics of ecological specialization in evolving E. coli populations. Nature 407:736-739.
Sniegowski PD, Gerrish PJ, Lenski RE (1997) Evolution of high mutation rates in experimental populations of Escherichia coli. Nature 387:703-705.
Blount ZD, Borland CZ, Lenski RE (2008) Historical contingency and the evolution of a key innovation in an experimental population of Escherichia coli. PNAS 105:7899-7906.
Schneider D, Duperchy E, Coursange E, Lenski RE, Blot M (2000) Long-term experimental evolution in Escherichia coli. IX. Characterization of IS-mediated mutations and rearrangements. Genetics 156:477-488.
Cooper TF, Rozen DE, Lenski RE (2003) Parallel changes in gene expression after 20,000 generations of evolution in E. coli. PNAS 100:1072-1077.
Woods R, Schneider D, Winkworth CL, Riley MA, Lenski RE (2006) Tests of parallel molecular evolution in a long-term experiment with Escherichia coli. PNAS 103:9107-9112. 8. Philippe N, Crozat E, Lenski RE, Schneider D (2007) Evolution of global regulatory networks during a long-term experiment with Escherichia coli. BioEssays 29:846-860.

Optimality and evolution of protein abundance levels in eukaryotes

Christian von Mering (SIB & University of Zurich)

The recent availability of large-scale shotgun proteomics data for a number of eukaryotes has provided us with a unique, unbiased view of the expressed eukaryotic proteome. We have recently applied "spectral counting" quantification techniques to this data to establish the relative composition of the core proteome, effectively quantifying protein molecules as rare as 1 part-per-million (ppm) abundance. We found that in the case of animals, the quantitative composition of the core proteome is remarkably well conserved, better than the composition of the transcriptome. From this observation, we infer that selection appears to act more strongly on protein levels, while allowing a certain degree of neutral "drift" on the absolute transcript abundance levels. I will discuss the extension of these observations to multiple organism, and how they relate to the functional network organization of the proteome.

Genomic Applications to the study of Human Microbiology

Karen E. Nelson (The J. Craig Venter Institute)

The human body is host to multitudes of microbial species and communities that are estimated to outnumber the number of host somatic cells. The ability to conduct metagenomic studies whereby we are generating sequence data from entire environments without first using a culturing step, has only been enhanced by the availability of 'next generation' sequencing technologies. A number of environments have been subject to metagenomic studies inclusive of the oceans and soils, and more recently there has been an intensive effort on to conduct metagenomic studies of the human body. The National Institutes of Health in the USA for example has launched a major Roadmap Initiative to determine if there is a core human microbiome, to understand correlations between health and disease and changes in the human microbiome, and to develop technological and bioinformatics tools to support these goals. The program is underway and includes significant reference genome sequencing and metagenomic sequencing to characterize the microbial communities from 15-18 body sites in a significant number of consented individuals. It is clear that the advent of metagenomics holds significant promise for increasing our understanding of many microbial diseases associated with the human body, inclusive of those that are yet to be characterized. From some of the initial studies, we have been able to identify novel virulence factors, and recreate a metabolic reconstruction. The microheterogeneity in the metagenomic data highlight the extent of microbial diversity associated with this environment.

A Domain Family Perspective on the Evolution of Protein Functions

Christine Orengo (University College London, UK)

We have established a classification of domain superfamilies (CATH-Gene3D) which recognises evolutionary relationships using evidence based on structural similarity, sequence similarity and functional properties of the domains. Gene3D contains domain structure predictions and functional annotations for nearly 700 completed genomes and 6.5 million protein sequences. CATH-Gene3D has been used to analyse the evolution of domain superfamilies and examine structural mechanisms by which the molecular functions of relatives within a superfamily have been modified. By studying 31 highly populated and structurally variable superfamilies we revealed the mechanisms by which secondary structure decorations to the common structural core, found in all superfamily relatives, can modify active site geometry or the domain surface thereby altering substrate specificity and/or domain/protein interactions (Reeves et al. JMB 2006). More recently we have analysed the HUP domain superfamily and catalogue in more precise detail the nature of structural changes apparent in different relatives within this superfamily which modify their functions. As well as characterising changes in molecular interactions (e.g. substrates/protein partners) we have also examined the extent to which duplicated superfamily relatives (paralogues) participate in different complexes and biological processes within E.Coli and yeast.

Searching for Signals of Past Migrations: Phoenician Expansion

Daniel E. Platt (IBM Thomas J. Watson Research Centre, NY, USA.)

Trade-driven and military expansions that established selective presence throughout some region of the world provides a criteria for distinguishing those genetic gradients that emerged from those specific migrations against a background of diverse migrations carrying similar genetic signals. Specifically, in trying to identify a genetic trace of the Phoenician expansions against a background including Greek trade, the Jewish Diaspora, and the Neolithic expansion, we are faced with all of these migrations having carried a similar mix of E1b1b's, J2's, and other genetic markers. For these migrations, we expected that the strongest signal would be from the male line. We found that Y haplogroups were too broad to yield the specificity we required. However, the STR micro-satellites have a sufficiently high mutation rate that diversity and specificity would be higher, and that the possibility of identifying lineages connected to the Lebenese heartland would provide supporting evidence to test the results of statistical tests. Given the high specificity, and allowing for 1-step STR mutations, we augmented the STRs by including their 1-step neighbors, calling these groups STR+'s. We expected that the signal would be weak following the collapse of the Phoenician trade network and the Punic Wars, but also determined that relatively weak signals from many colonies and trade sites, which might only like 0.1 and 0.3 percent of the time, are much less likely to have occurred say 5 out of 8 tested sites, in a way that would be distributed as a simple binomial. Following this line of reasoning, we identified a number of STR+ haplotype groups from multiple haplogroups that scored relatively well across a wide range of Phoenician sites, but which scored poorly across the Greek colony sites. These STR+'s were primarily closely related to each other, with their roots contained within the Phoenician heartland, and with a scope suggesting a MRCA several thousand years prior to the Phoenician trade expansion.

The Physcomitrella Genome Reveals Evolutionary Insights into the Conquest of Land by Plants

Stefan Rensing (University of Freiburg, Germany)

The genome sequence of the model moss Physcomitrella patens was compared to those of flowering plants, from which it is separated by more than 450 million years, and unicellular aquatic algae. This comparison revealed genomic changes concomitant with the evolutionary movement to land, including a general increase in gene family complexity; loss of genes associated with aquatic environments; acquisition of genes for tolerating terrestrial stresses; and the development of phytohormone signaling pathways for coordinating multicellular growth and dehydration response. The Physcomitrella genome also enriches cross-genome comparisons of plant genome evolution, particularly with respect to transcriptional regulation. This genome provides a resource for evo-devo inferences and for experimental analysis of plant processes through this plant's unique facility for reverse genetics. Future prospects of developing Physcomitrella as a reference genome will be presented.

Convergent genotypic evolution and the origin of C4 photosynthesis in plants

Nicolas Salamin (SIB & University of Lausanne)

Phenotypic convergence is a widespread and well-recognized evolutionary phenomenon. However, the responsible molecular mechanisms remain often unknown mainly because the genes involved are not identified. A well-known example of physiological convergence is the C4 photosynthetic pathway, which evolved independently more than 45 times in flowering plants. Grasses have almost 60% of existing C4 species and they were used as an ideal study group to understand the evolution of this pathway. The molecular evolution of several key genes involved in the C4 pathway in grasses were characterized. Very high level of positive selection could be detected in all genes investigated and demonstrated very strong events of convergent genotypic evolution. The recruitment of C4 adapted gene lineages further followed a complex evolutionary pattern. The data gathered was also used to test specific hypotheses explaining the sudden appearance of C4 in plant evolutionary history.

The antigenic evolution of influenza viruses

Derek Smith (University of Cambridge, UK)

Thirty plus years of global influenza virus surveillance, in multiple species, provides a remarkable dataset for the study of influenza virus evolution. Because the purpose of much of this surveillance is vaccine strain selection, these data have been analyzed antigenically as well as genetically. I will describe the antigenic evolution of influenza A(H3N2) viruses from the influenza pandemic in 1968 to present, including examples of the influenza vaccine strain selection process. This evolution of human influenza viruses will be contrasted with studies in pigs and birds, to show the importance of the immunity in the host population on the evolution of the virus.

Retrieval of ancient DNA from fossil remains

Eske Willerslev (University of Copenhagen, Denmark)

In the past two decades, ancient DNA research has progressed from the retrieval of small fragments of mitochondrial DNA from a few late Holocene specimens, to large-scale studies of ancient populations, phenotypically important nuclear loci, and even genome scale sequencing of extinct species. However, the field is still regularly marred by erroneous reports, which underestimate the extent of contamination within laboratories and samples themselves. An improved understanding of these processes and the effects of damage on ancient DNA templates has started to provide a more robust basis for research. Recent methodological advances have included the characterization of Pleistocene mammal populations and discoveries of DNA preserved in ancient hair, coprolites, sediments, and ice. These have changed our understanding of human migration into the New World and the palaeoecology of Greenland. Increasingly, ancient genetic information is providing a unique means to test assumptions used in evolutionary and population genetics studies to reconstruct the past. With the advent and uptake of appropriate methodologies, ancient DNA is now positioned to become a powerful tool in biological research.