Periodic Reporting for period 3 - DECAF (Deciphering adaptive footprints of epiC evolution on different timescales)
Periodo di rendicontazione: 2023-01-01 al 2024-06-30
This project investigates how epigenetic modifications leave imprints on the genetic level and how this translates into the evolutionary process.
Genetic information can be temporarily modified, for example as a consequence of a responses to environmental changes. These changes are called epigenetic changes and they have a pivotal function in cell regulation and an organism in general. It is widely believed that such epigenetic responses may have an adaptive character and help organisms to cope with new environments. It is however unclear what role these changes have over longer evolutionary times. This is because genetic information is passed on from one generation to the next, which is not necessarily true for epigenetic changes. The aim of this project is to identify adaptive epigenetic characters and elucidate their role in the evolutionary process.
Here we use a specific epigenetic modification of DNA - DNA methylation - to understand how non-permanent changes of DNA have an impact on the long-term genome evolution. This is highly debated, because in humans and other animals epigenetic non-permanent changes are usually not inherited and therefore do not contribute to the next generation. We use birds as models to understand these rapid changes, because their DNA methylation mechanisms are similar to humans, but their genomes are more compact which allows easier identification of potentially functional elements.
Overall, we aim to approach the epigenetic consequences of DNA methylation on evolution at three levels. First, we want to understand how epigenetic changes in early development translate in long-term evolutionary sequence changes. The important reasons to investigate this is that in mammals (such as humans) and birds, reproductive cells - the germline - is separated from other somatic cells early in development. However, in the critical early phase before this separation takes place modifications of the epigenetic pattern will potentially contribute to the next generation as well as to changes in the soma. A second additional important side aspect considers a special feature of song bird genomics. Songbirds possess a separate chromosome in the germline, and it is important to understand how this is regulated in early development. It is believed that this special chromosome might be a mechanism to counteract the deleterious effects of ageing – which is related to a major theory of ageing developed around 70 years ago called the antagonistic pleiotropy of ageing.
The second aspect we are investigating is how epigenetic and genetic diversity interplay. Selection can only act when there are differences between individuals – and we know that most individuals genetically differ. What we do not know how much variation there is in the epigenetic patterns, so for example is there a lot of epigenetic variation when there is little genetic variation to compensate. While it is possible to obtain genetic and epigenetic modifications, current methods have technical caveats which do not allow to obtain genetic and epigenetic diversity at the same time from the same individual with high precision. We want to apply novel methods that address these limitations. Furthermore, there is compelling evidence that DNA methylation marks may be heterogenous themselves which add another layer of technical challenge. The core question we want to answer is whether epigenetic modifications are under selection and if so what genetic imprints would this leave on the genome.
The third aspect we want to understand is whether epigenetic modification can contribute to species diversification. This is because epigenetic modification lead to higher mutation rates which means that sites that are prone to epigenetic modifications would tend to diversify fastest between species. The second aspect we want to understand is the interplay in the process of hybridization (i.e. when two genetically diverged species produce offspring). Because sites that can be modified by epigenetics are prone to accumulate mutations faster, they might be causing incompatibilities when hybrids are formed. This work is conducted through simulations and the study of hybrid individuals of songbird populations.
Our research on the fundamentals of epigenetics is important for society because it has direct links to ageing, climate change and disease biology. It is known that epigenetic regulation is fundamental to how organisms respond to environmental changes, stress and it has a major role in disease biology, such as cancers.
Another important aspect is that our research is relevant for human mechanisms of epigenetics. We want to understand how epigenetic changes in early development translate into long-term evolutionary mechanisms. While our study organisms are various bird species, their mode of epigenetic modification is similar to humans. We therefore expect that our results can be applied to humans as well.
A further aspect we want to develop is how epigenetic and genetic diversity interplay. This is in particular important as rapid changes of climatic conditions will require rapid regulatory responses. This is also interrelated to the third project part where we investigate how novel genetic variation obtained through hybridization with other species is modulated by epigenetic mechanisms.
Genetic information can be temporarily modified, for example as a consequence of a responses to environmental changes. These changes are called epigenetic changes and they have a pivotal function in cell regulation and an organism in general. It is widely believed that such epigenetic responses may have an adaptive character and help organisms to cope with new environments. It is however unclear what role these changes have over longer evolutionary times. This is because genetic information is passed on from one generation to the next, which is not necessarily true for epigenetic changes. The aim of this project is to identify adaptive epigenetic characters and elucidate their role in the evolutionary process.
Here we use a specific epigenetic modification of DNA - DNA methylation - to understand how non-permanent changes of DNA have an impact on the long-term genome evolution. This is highly debated, because in humans and other animals epigenetic non-permanent changes are usually not inherited and therefore do not contribute to the next generation. We use birds as models to understand these rapid changes, because their DNA methylation mechanisms are similar to humans, but their genomes are more compact which allows easier identification of potentially functional elements.
Overall, we aim to approach the epigenetic consequences of DNA methylation on evolution at three levels. First, we want to understand how epigenetic changes in early development translate in long-term evolutionary sequence changes. The important reasons to investigate this is that in mammals (such as humans) and birds, reproductive cells - the germline - is separated from other somatic cells early in development. However, in the critical early phase before this separation takes place modifications of the epigenetic pattern will potentially contribute to the next generation as well as to changes in the soma. A second additional important side aspect considers a special feature of song bird genomics. Songbirds possess a separate chromosome in the germline, and it is important to understand how this is regulated in early development. It is believed that this special chromosome might be a mechanism to counteract the deleterious effects of ageing – which is related to a major theory of ageing developed around 70 years ago called the antagonistic pleiotropy of ageing.
The second aspect we are investigating is how epigenetic and genetic diversity interplay. Selection can only act when there are differences between individuals – and we know that most individuals genetically differ. What we do not know how much variation there is in the epigenetic patterns, so for example is there a lot of epigenetic variation when there is little genetic variation to compensate. While it is possible to obtain genetic and epigenetic modifications, current methods have technical caveats which do not allow to obtain genetic and epigenetic diversity at the same time from the same individual with high precision. We want to apply novel methods that address these limitations. Furthermore, there is compelling evidence that DNA methylation marks may be heterogenous themselves which add another layer of technical challenge. The core question we want to answer is whether epigenetic modifications are under selection and if so what genetic imprints would this leave on the genome.
The third aspect we want to understand is whether epigenetic modification can contribute to species diversification. This is because epigenetic modification lead to higher mutation rates which means that sites that are prone to epigenetic modifications would tend to diversify fastest between species. The second aspect we want to understand is the interplay in the process of hybridization (i.e. when two genetically diverged species produce offspring). Because sites that can be modified by epigenetics are prone to accumulate mutations faster, they might be causing incompatibilities when hybrids are formed. This work is conducted through simulations and the study of hybrid individuals of songbird populations.
Our research on the fundamentals of epigenetics is important for society because it has direct links to ageing, climate change and disease biology. It is known that epigenetic regulation is fundamental to how organisms respond to environmental changes, stress and it has a major role in disease biology, such as cancers.
Another important aspect is that our research is relevant for human mechanisms of epigenetics. We want to understand how epigenetic changes in early development translate into long-term evolutionary mechanisms. While our study organisms are various bird species, their mode of epigenetic modification is similar to humans. We therefore expect that our results can be applied to humans as well.
A further aspect we want to develop is how epigenetic and genetic diversity interplay. This is in particular important as rapid changes of climatic conditions will require rapid regulatory responses. This is also interrelated to the third project part where we investigate how novel genetic variation obtained through hybridization with other species is modulated by epigenetic mechanisms.
For WP1, which investigates early developmental epigenetics, it was necessary to setup an experimental workflow as well as a running field site to study epigenetic modifications of wild species. In order to get a sufficient number of samples we set up a field site in a forest in Northern Germany to study blue tit and great tits in natural habitats. In particular we extended an existing field site by more than 100 nestboxes (now 150 nestboxes) for blue tits and great tits which allowed us to obtain around 1,000 bird samples over the duration of two breeding seasons. This is the first time that epigenetic patterns of wild living populations are studied on such a detail. We combine this work with samples from domesticated species from our collaborators, for which we obtained additional 300 samples, and had ongoing sample input of zebra finches which were kept in in-house aviaries. We paved the way to combine ecological, molecular and bioinformatic work to understand how epigenetic modification are altered through early development. We now established a laboratory setup for which we use a cell sorting approach based on antibody staining, which is not very common in ecological genetics. These methods needed substantial troubleshooting and optimization and are now ready to be used on a largescale time-series for which the above-mentioned samples will be used.
For project WP2 we developed the theoretical underpinnings of how selection of epigenetic modifications should translate into genetic differentiation over long evolutionary times within and across species. For empirical testing a novel sequencing technology will be applied which we are currently setting up in our lab. A new member that recently joined the lab will exclusively work on this.
For project WP3 we were able to obtain samples from great tit hybrid individuals which we are currently running a comprehensive set of population genomic analyses. For this we use methods of genetic differentiation analysis to disentangle the long-term effect of epigenetic heterogeneity on the sequence evolution. We will also identify regions of high epigenetic and genetic differentiation in hybrids.
For project WP2 we developed the theoretical underpinnings of how selection of epigenetic modifications should translate into genetic differentiation over long evolutionary times within and across species. For empirical testing a novel sequencing technology will be applied which we are currently setting up in our lab. A new member that recently joined the lab will exclusively work on this.
For project WP3 we were able to obtain samples from great tit hybrid individuals which we are currently running a comprehensive set of population genomic analyses. For this we use methods of genetic differentiation analysis to disentangle the long-term effect of epigenetic heterogeneity on the sequence evolution. We will also identify regions of high epigenetic and genetic differentiation in hybrids.
A major outcome will be that we were able to disentangle epigenetic and genetic contribution to the evolutionary process at a very high resolution. Ultimately, we will be able to answer which one is more important and on what time scale. At the moment, consequences of epigenetics are highly neglected in the evolutionary process. Ideally some of our results might be applicable to tackle human disease.
For WP1 the expected major result will be that we will have a detailed time-series of epigenetic modification in early development derived from germline cells for five different avian species. This would allow us to pinpoint epigenetic sites with evolutionary conserved features that directly contribute to the next generation. We will also understand the dynamics of a special chromosome in the avian germline and its role in regulation which is believed to have implication for the process of ageing.
For WP2 we will be able to disentangle genetic along with epigenetic variation in specific avian populations. How are these correlated and does epigenetic diversity compensate for genetic diversity will be one of many intriguing questions that we will be able to answer. This has direct implications on how organisms adapt to environmental changes.
For WP3 we will understand the evolutionary consequences of novel genetic and epigenetic diversity through the process of hybridization. Are epigenetic modifications facilitators or inhibitors of hybrid formation? Are novel epigenetic modifications that have been obtained through hybridization involved in adaptive processes? Ultimately, we will understand whether novel adaptive epigenetic variation obtained through hybridization is a major contributor to long-term evolution.
For WP1 the expected major result will be that we will have a detailed time-series of epigenetic modification in early development derived from germline cells for five different avian species. This would allow us to pinpoint epigenetic sites with evolutionary conserved features that directly contribute to the next generation. We will also understand the dynamics of a special chromosome in the avian germline and its role in regulation which is believed to have implication for the process of ageing.
For WP2 we will be able to disentangle genetic along with epigenetic variation in specific avian populations. How are these correlated and does epigenetic diversity compensate for genetic diversity will be one of many intriguing questions that we will be able to answer. This has direct implications on how organisms adapt to environmental changes.
For WP3 we will understand the evolutionary consequences of novel genetic and epigenetic diversity through the process of hybridization. Are epigenetic modifications facilitators or inhibitors of hybrid formation? Are novel epigenetic modifications that have been obtained through hybridization involved in adaptive processes? Ultimately, we will understand whether novel adaptive epigenetic variation obtained through hybridization is a major contributor to long-term evolution.