Project acronym Evoland
Project Evolution of regulatory landscapes at multiple timescales
Researcher (PI) Jose Luis GOMEZ-SKARMETA
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Advanced Grant (AdG), LS8, ERC-2016-ADG
Summary Evolution of animal morphology relies on changes in developmental programs that control body plans and organ shape. Such changes are thought to arise form alteration of the expression of functionally conserved developmental genes and their vast downstream networks. Although this hypothesis has a profound impact on the way we view animal evolution, final proof is still lacking. The hypothesis calls for evolution to take place mainly through modifications of cis-regulatory elements (CREs) controlling gene expression. However, these genomic regions are precisely those that we understand the least and, until recently, basic knowledge on how regulatory information is organized in the 3D genome or how to spatio-temporally assign CREs to their target genes was unknown.
The advent of next generation sequencing-based tools has made possible to identify genome-wide CREs and reveal how they are organized in the 3D genome. But this new knowledge has been largely ignored by most hypotheses on the evolution of gene expression, development and animal morphology. These new high-throughput methods have been mainly restricted to selected model organisms, and due to the lack of sequence conservation of CREs across lineages, we still have very limited information about the impact of CREs on animal morphology evolution.
By integrating in a systematic and phylogenetically driven manner the contribution of CREs and their 3D organization to animal morphology at different evolutionary scales, we will for the first time link evolution, regulatory information, genome 3D architecture and morphology. We will apply this strategy to study animal morphology along the evolution of deuterostome body plans, the generation of fin morphological diversity in vertebrates, and the recent phenotypic changes in fish adapted to cave environments.
Our proposal will make ground-breaking advances in our understanding of the global principles underlying the evolution of cis-regulatory DNA and animal form.
Summary
Evolution of animal morphology relies on changes in developmental programs that control body plans and organ shape. Such changes are thought to arise form alteration of the expression of functionally conserved developmental genes and their vast downstream networks. Although this hypothesis has a profound impact on the way we view animal evolution, final proof is still lacking. The hypothesis calls for evolution to take place mainly through modifications of cis-regulatory elements (CREs) controlling gene expression. However, these genomic regions are precisely those that we understand the least and, until recently, basic knowledge on how regulatory information is organized in the 3D genome or how to spatio-temporally assign CREs to their target genes was unknown.
The advent of next generation sequencing-based tools has made possible to identify genome-wide CREs and reveal how they are organized in the 3D genome. But this new knowledge has been largely ignored by most hypotheses on the evolution of gene expression, development and animal morphology. These new high-throughput methods have been mainly restricted to selected model organisms, and due to the lack of sequence conservation of CREs across lineages, we still have very limited information about the impact of CREs on animal morphology evolution.
By integrating in a systematic and phylogenetically driven manner the contribution of CREs and their 3D organization to animal morphology at different evolutionary scales, we will for the first time link evolution, regulatory information, genome 3D architecture and morphology. We will apply this strategy to study animal morphology along the evolution of deuterostome body plans, the generation of fin morphological diversity in vertebrates, and the recent phenotypic changes in fish adapted to cave environments.
Our proposal will make ground-breaking advances in our understanding of the global principles underlying the evolution of cis-regulatory DNA and animal form.
Max ERC Funding
2 499 514 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym MATURATION
Project Age at maturity in Atlantic salmon: molecular and ecological dissection of an adaptive trait
Researcher (PI) Craig PRIMMER
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Advanced Grant (AdG), LS8, ERC-2016-ADG
Summary Life history is the nexus of biology, because various biological questions ultimately revolve around the causes and consequences of variation in reproduction and survival, i.e. fitness. Traditionally, a major tool in life-history research has been quantitative genetics because it provides an important statistical link between phenotype and genotype. However, the mechanisms by which evolution occurs may remain unclear unless such traditional approaches are combined with molecular investigations. Another complicating factor is that the fitness of male vs female life histories do not always align, and hence life history traits may be shaped by sexual conflict. This is why life-history approaches focusing on both quantifying the conflict and understanding its resolution at the genetic level are needed.
As in many species, age at maturity in Atlantic salmon is tightly linked with size at maturity and thus represents a classic evolutionary trade-off: later maturing individuals spend more time at sea before returning to freshwater to spawn and have higher reproductive success due to their larger size but also have a higher risk of dying prior to first reproduction. Our recent cover paper in Nature reported a large-effect gene explaining 40% of the variation in this key life history trait. Remarkably, the locus exhibits sex-dependent dominance and this resolves a potential intra-locus sexual conflict in the species. The relatively simple genetic architecture of this trait combined with the features of Atlantic salmon as a model system offer an ideal opportunity to better understand the molecular mechanisms and ecological drivers underlying a locally adapted life history trait.
In MATURATION I will i) characterize age at maturity candidate gene functions and allelic effects on phenotypes ii) elucidate fitness effects of these phenotypes and GxE interactions iii) develop a mechanistic model for the sex-dependent dominance and validate intra-locus sexual conflict resolution
Summary
Life history is the nexus of biology, because various biological questions ultimately revolve around the causes and consequences of variation in reproduction and survival, i.e. fitness. Traditionally, a major tool in life-history research has been quantitative genetics because it provides an important statistical link between phenotype and genotype. However, the mechanisms by which evolution occurs may remain unclear unless such traditional approaches are combined with molecular investigations. Another complicating factor is that the fitness of male vs female life histories do not always align, and hence life history traits may be shaped by sexual conflict. This is why life-history approaches focusing on both quantifying the conflict and understanding its resolution at the genetic level are needed.
As in many species, age at maturity in Atlantic salmon is tightly linked with size at maturity and thus represents a classic evolutionary trade-off: later maturing individuals spend more time at sea before returning to freshwater to spawn and have higher reproductive success due to their larger size but also have a higher risk of dying prior to first reproduction. Our recent cover paper in Nature reported a large-effect gene explaining 40% of the variation in this key life history trait. Remarkably, the locus exhibits sex-dependent dominance and this resolves a potential intra-locus sexual conflict in the species. The relatively simple genetic architecture of this trait combined with the features of Atlantic salmon as a model system offer an ideal opportunity to better understand the molecular mechanisms and ecological drivers underlying a locally adapted life history trait.
In MATURATION I will i) characterize age at maturity candidate gene functions and allelic effects on phenotypes ii) elucidate fitness effects of these phenotypes and GxE interactions iii) develop a mechanistic model for the sex-dependent dominance and validate intra-locus sexual conflict resolution
Max ERC Funding
2 500 000 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym MetaPG
Project Culture-free strain-level population genomics to identify disappearing human-associated microbes in the westernized world
Researcher (PI) Nicola SEGATA
Host Institution (HI) UNIVERSITA DEGLI STUDI DI TRENTO
Call Details Starting Grant (StG), LS8, ERC-2016-STG
Summary Investigating symbiotic gut microbes with large-scale comparative genomics would allow gaining crucial insights into the “epidemiology”, genetic diversity, and population structure of hundreds of scarcely characterized microorganisms. However, cultivation-based approaches are ineffective at targeting the large fraction of the gut microbial diversity that is hard be grown in vitro. They are also expensive and time consuming, as they need sampling specific bacteria from geographically separated subjects. On the other hand, cultivation-free metagenomic data is now available for thousands of stool samples collected worldwide, but they are not currently exploited for strain-level microbial population genomics because of the lack of suitable computational methods. In Aim1, we leverage our expertise in computational biology to bridge the gap between the fields of metagenomics and population genomics by developing novel and highly innovative methodologies to extract strain-level genomic and genetic profiles from metagenomic samples with the resolution needed by comparative genomics. Such paradigmatic shift will put us in the position of reusing in Aim2 the thousands of available metagenomes and unravel for the first time the population structure of hundreds of uncultivable gut microbes. Among the novel tasks enabled, we will focus in Aim3 on identifying those microbial strains that are currently disappearing in westernized populations as a consequence of urbanization, industrialization, high-fat diets. We will complement the available data with gut metagenomes from novel targeted cohorts of both westernized and non-westernized populations. Our project defines the foundation for cultivation-free strain-level population genomics, provides comparative genomics results with unprecedented resolution for hundreds of under-investigated microbes, and compiles a catalogue of strains undergoing or at risk of primary, secondary, or ecological extinction in westernized populations.
Summary
Investigating symbiotic gut microbes with large-scale comparative genomics would allow gaining crucial insights into the “epidemiology”, genetic diversity, and population structure of hundreds of scarcely characterized microorganisms. However, cultivation-based approaches are ineffective at targeting the large fraction of the gut microbial diversity that is hard be grown in vitro. They are also expensive and time consuming, as they need sampling specific bacteria from geographically separated subjects. On the other hand, cultivation-free metagenomic data is now available for thousands of stool samples collected worldwide, but they are not currently exploited for strain-level microbial population genomics because of the lack of suitable computational methods. In Aim1, we leverage our expertise in computational biology to bridge the gap between the fields of metagenomics and population genomics by developing novel and highly innovative methodologies to extract strain-level genomic and genetic profiles from metagenomic samples with the resolution needed by comparative genomics. Such paradigmatic shift will put us in the position of reusing in Aim2 the thousands of available metagenomes and unravel for the first time the population structure of hundreds of uncultivable gut microbes. Among the novel tasks enabled, we will focus in Aim3 on identifying those microbial strains that are currently disappearing in westernized populations as a consequence of urbanization, industrialization, high-fat diets. We will complement the available data with gut metagenomes from novel targeted cohorts of both westernized and non-westernized populations. Our project defines the foundation for cultivation-free strain-level population genomics, provides comparative genomics results with unprecedented resolution for hundreds of under-investigated microbes, and compiles a catalogue of strains undergoing or at risk of primary, secondary, or ecological extinction in westernized populations.
Max ERC Funding
1 499 482 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym RETVOLUTION
Project Reticulate evolution: patterns and impacts of non-vertical inheritance in eukaryotic genomes.
Researcher (PI) Juan Antonio Gabaldón Estevan
Host Institution (HI) FUNDACIO CENTRE DE REGULACIO GENOMICA
Call Details Consolidator Grant (CoG), LS8, ERC-2016-COG
Summary The traditional view is that species and their genomes evolve only by vertical descent, leading to evolutionary histories that can be represented by bifurcating lineages. However, modern evolutionary thinking recognizes processes of reticulate evolution, such as horizontal gene transfer or hybridization, which involve total or partial merging of genetic material from two diverged species. Today it is widely recognized that such events are rampant in prokaryotes, but a relevant role in eukaryotes has only recently been acknowledged. Unprecedented genomic and phylogenetic information, and recent work from others and us have shown that reticulate evolution in eukaryotes is more common and have more complex outcomes than previously thought. However, we still have a very limited understanding of what are the impacts at the genomic and evolutionary levels. To address this, I propose to combine innovative computational and experimental approaches. The first goal is to infer patterns of reticulate evolution across the eukaryotic tree, and relate this to current biological knowledge. The second goal is to trace the genomic aftermath of inter-species hybridization at the i) long-term, by analysing available genomes in selected eukaryotic taxa, ii) mid-term, by sequencing lineages of natural fungal hybrids, and iii) short-term, by using re-sequencing and experimental evolution in yeast. A particular focus is placed on elucidating the role of hybridization in the origin of whole genome duplications, and in facilitating the spread of horizontally transferred genes. Finally results from this and other projects will be integrated into emerging theoretical frameworks. Outcomes of this project will profoundly improve our understanding of reticular processes as drivers of eukaryotic genome evolution, and will impact other key aspects of evolutionary theory, ranging from the concept of orthology to the eukaryotic tree of life.
Summary
The traditional view is that species and their genomes evolve only by vertical descent, leading to evolutionary histories that can be represented by bifurcating lineages. However, modern evolutionary thinking recognizes processes of reticulate evolution, such as horizontal gene transfer or hybridization, which involve total or partial merging of genetic material from two diverged species. Today it is widely recognized that such events are rampant in prokaryotes, but a relevant role in eukaryotes has only recently been acknowledged. Unprecedented genomic and phylogenetic information, and recent work from others and us have shown that reticulate evolution in eukaryotes is more common and have more complex outcomes than previously thought. However, we still have a very limited understanding of what are the impacts at the genomic and evolutionary levels. To address this, I propose to combine innovative computational and experimental approaches. The first goal is to infer patterns of reticulate evolution across the eukaryotic tree, and relate this to current biological knowledge. The second goal is to trace the genomic aftermath of inter-species hybridization at the i) long-term, by analysing available genomes in selected eukaryotic taxa, ii) mid-term, by sequencing lineages of natural fungal hybrids, and iii) short-term, by using re-sequencing and experimental evolution in yeast. A particular focus is placed on elucidating the role of hybridization in the origin of whole genome duplications, and in facilitating the spread of horizontally transferred genes. Finally results from this and other projects will be integrated into emerging theoretical frameworks. Outcomes of this project will profoundly improve our understanding of reticular processes as drivers of eukaryotic genome evolution, and will impact other key aspects of evolutionary theory, ranging from the concept of orthology to the eukaryotic tree of life.
Max ERC Funding
1 986 178 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym Vis-a-Vis
Project Collective Infectious Units and the Social Evolution of Viruses
Researcher (PI) Rafael SANJUAN VERDEGUER
Host Institution (HI) UNIVERSITAT DE VALENCIA
Call Details Consolidator Grant (CoG), LS8, ERC-2016-COG
Summary A widely accepted view in virology is that virions function as independent infectious units. However, recent work by us and others indicates that viruses are often transmitted as more complex structures, such as virion aggregates, lipid vesicles or protein matrices harbouring multiple infectious particles. This demonstrates that viruses can be transmitted as “collective infectious units”, in sharp contrast with the current paradigm. Critically, these recent discoveries now set the stage for the evolution of social interactions, a previously unappreciated facet of viruses. I propose to investigate how collective infectious units drive virus social evolution using state-of-the-art tools from the fields of virology, genetics, structural biology, and nanotechnology. The effects of collective infectivity on viral fitness will be tested directly using experimental evolution and genetic engineering, and confirmed in vivo. Three widely different viruses will be used to achieve generality: human enteroviruses, a vector-borne rhabdovirus, and a baculovirus. Furthermore, the implications of virus social interactions for the maintenance of genetic diversity, evolvability, virulence evolution, and the emergence of drug resistance will be investigated. Radically new processes such as the putative extracellular fusion of viral particles will be also explored. I expect that infectious units constituted by viruses from different species will be uncovered as well, with far-reaching implications for epidemiology. It is becoming increasingly recognized that parasite sociality is a disease determinant, and our results may therefore inspire new antiviral strategies. In sum, this project aims at laying the foundations of virus sociality from a mechanistically-informed, bottom-up approach. Importantly, beyond their practical importance viruses will also provide a simple and tractable system that will help us to establish more general principles of social evolution.
Summary
A widely accepted view in virology is that virions function as independent infectious units. However, recent work by us and others indicates that viruses are often transmitted as more complex structures, such as virion aggregates, lipid vesicles or protein matrices harbouring multiple infectious particles. This demonstrates that viruses can be transmitted as “collective infectious units”, in sharp contrast with the current paradigm. Critically, these recent discoveries now set the stage for the evolution of social interactions, a previously unappreciated facet of viruses. I propose to investigate how collective infectious units drive virus social evolution using state-of-the-art tools from the fields of virology, genetics, structural biology, and nanotechnology. The effects of collective infectivity on viral fitness will be tested directly using experimental evolution and genetic engineering, and confirmed in vivo. Three widely different viruses will be used to achieve generality: human enteroviruses, a vector-borne rhabdovirus, and a baculovirus. Furthermore, the implications of virus social interactions for the maintenance of genetic diversity, evolvability, virulence evolution, and the emergence of drug resistance will be investigated. Radically new processes such as the putative extracellular fusion of viral particles will be also explored. I expect that infectious units constituted by viruses from different species will be uncovered as well, with far-reaching implications for epidemiology. It is becoming increasingly recognized that parasite sociality is a disease determinant, and our results may therefore inspire new antiviral strategies. In sum, this project aims at laying the foundations of virus sociality from a mechanistically-informed, bottom-up approach. Importantly, beyond their practical importance viruses will also provide a simple and tractable system that will help us to establish more general principles of social evolution.
Max ERC Funding
1 969 821 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
