Periodic Reporting for period 1 - InterChromaTE (Interactions between chromatin and transposable elements in rapid adaptation to environmental stress)
Período documentado: 2021-09-16 hasta 2023-09-15
Human activity is changing the global climate, and environmental stresses such as rising temperatures and heat waves are affecting many species. Biologists want to understand how different organisms cope with these changes: whether individuals can adjust their physiology to withstand stressful environments (a process known as acclimation), and whether populations can evolve over many generations to thrive in these changing environments (a process known as adaptation).
Two biological factors that could affect acclimation and adaptation are the epigenome and transposable elements (TEs). The epigenome consists of molecular changes to the structure and expression of the genome (the genome being the entire ensemble of an organism’s genes which is found in all nucleated cells), while TEs are fragments of genomic DNA that can replicate independently and insert themselves into new locations, giving natural selection new genetic variation to act on. These two factors interact: new TE insertions can influence gene expression through interactions with the epigenome, and both epigenomic change and TE activity are sensitive to environmental stresses such as heat shock. Understanding these interactions, and how they differ between populations, is therefore a key step in explaining how different organisms respond to global change.
Despite this, little is known about how interactions between environmental stress, the epigenome and transposable elements play out in natural populations. In the InterChromaTE project, I aimed to improve our understanding of these interactions and their potential evolutionary consequences. To do so, I measured natural population variation in TEs and a key epigenome trait, chromatin accessibility, which is linked to gene expression; I investigated whether differences influenced molecular and phenotypic responses to heat shock; and I explored whether heat stress responses could be transgenerationally inherited. To answer these questions, I used the fruit fly Drosophila, which due to its rapid life cycle and well-studied genome, made an ideal model organism.
My experiments showed that heat shock leads to clear changes in chromatin accessibility, gene expression and phenotype, and that these responses differ between populations. The relationship between chromatin accessibility and gene expression appeared to be influenced by the presence of TEs, an effect that also differed between populations. In one population, heat shock altered gene expression and phenotype not only in the stressed individuals, but in their great-grand offspring, highlighting an important transgenerational effect. Although chromatin accessibility did not seem to regulate this, it may be the result of an alternative epigenetic mechanism. Together, these results show the important role epigenome-TE interactions can play in the regulation of environmental stress responses, and how they have the potential to influence evolution through transgenerationally inherited phenotypes.
Two biological factors that could affect acclimation and adaptation are the epigenome and transposable elements (TEs). The epigenome consists of molecular changes to the structure and expression of the genome (the genome being the entire ensemble of an organism’s genes which is found in all nucleated cells), while TEs are fragments of genomic DNA that can replicate independently and insert themselves into new locations, giving natural selection new genetic variation to act on. These two factors interact: new TE insertions can influence gene expression through interactions with the epigenome, and both epigenomic change and TE activity are sensitive to environmental stresses such as heat shock. Understanding these interactions, and how they differ between populations, is therefore a key step in explaining how different organisms respond to global change.
Despite this, little is known about how interactions between environmental stress, the epigenome and transposable elements play out in natural populations. In the InterChromaTE project, I aimed to improve our understanding of these interactions and their potential evolutionary consequences. To do so, I measured natural population variation in TEs and a key epigenome trait, chromatin accessibility, which is linked to gene expression; I investigated whether differences influenced molecular and phenotypic responses to heat shock; and I explored whether heat stress responses could be transgenerationally inherited. To answer these questions, I used the fruit fly Drosophila, which due to its rapid life cycle and well-studied genome, made an ideal model organism.
My experiments showed that heat shock leads to clear changes in chromatin accessibility, gene expression and phenotype, and that these responses differ between populations. The relationship between chromatin accessibility and gene expression appeared to be influenced by the presence of TEs, an effect that also differed between populations. In one population, heat shock altered gene expression and phenotype not only in the stressed individuals, but in their great-grand offspring, highlighting an important transgenerational effect. Although chromatin accessibility did not seem to regulate this, it may be the result of an alternative epigenetic mechanism. Together, these results show the important role epigenome-TE interactions can play in the regulation of environmental stress responses, and how they have the potential to influence evolution through transgenerationally inherited phenotypes.
In order to answer the project objectives, I carried out experiments on natural populations of Drosophila. The first experiment compared four populations of Drosophila melanogaster: three from Spain, and one from Finland. I identified differences in thermal tolerance between the populations and measured variation in chromatin accessibility and new TE insertions. I also carried out a heat shock experiment for two populations with different thermal tolerances (one from Spain and one from Finland), and measured how patterns of chromatin accessibility and gene expression in female ovaries changed after a short sharp heat shock, and how development in the offspring was affected. Finally, after three generations, I re-measured chromatin accessibility, gene expression and offspring development to test for transgenerational effects of heat shock. In a second experiment, I acquired 6 different strains of the invasive species Drosophila suzukii. Two of these strains were from the species’ native range in Japan, and four were from invasive populations in Europe and North America. I measured chromatin accessibility and TE variability to search for signatures of invasiveness in their associations.
TEs and chromatin varied across the four populations tested. I found that chromatin accessibility played a key role in regulating the response to heat shock, and that gene regulation and gene expression differed between populations of D. melanogaster. Flies from the more thermally tolerant population (Spain) showed fewer changes in gene expression and more changes in chromatin accessibility than those from the less thermally tolerant population (Finland). We also identified a potential interaction between TEs and chromatin: the epigenomic regulation of genes near to TEs was disrupted in the Finnish population, but not the Spanish one. Heat shock also led to developmental differences, and in the Spanish population, was potentially beneficial (development was more rapid). Furthermore, this potentially beneficial response was still detected after three generations, implying transgenerational inheritance, although most heat shock induced changes in chromatin accessibility had disappeared.
These findings from D. melanogaster are being prepared for submission to a high profile scientific journal later this year. Results from the comparison of invasive and native strains of D. suzukii are still being analysed but will also be submitted to a high profile scientific journal in 2024. During this project, I also initiated and lead a collaborative team of researchers from several different institutes in reviewing the state of the art in our understanding of interactions between the epigenome and genome. This review is currently undergoing peer review.
TEs and chromatin varied across the four populations tested. I found that chromatin accessibility played a key role in regulating the response to heat shock, and that gene regulation and gene expression differed between populations of D. melanogaster. Flies from the more thermally tolerant population (Spain) showed fewer changes in gene expression and more changes in chromatin accessibility than those from the less thermally tolerant population (Finland). We also identified a potential interaction between TEs and chromatin: the epigenomic regulation of genes near to TEs was disrupted in the Finnish population, but not the Spanish one. Heat shock also led to developmental differences, and in the Spanish population, was potentially beneficial (development was more rapid). Furthermore, this potentially beneficial response was still detected after three generations, implying transgenerational inheritance, although most heat shock induced changes in chromatin accessibility had disappeared.
These findings from D. melanogaster are being prepared for submission to a high profile scientific journal later this year. Results from the comparison of invasive and native strains of D. suzukii are still being analysed but will also be submitted to a high profile scientific journal in 2024. During this project, I also initiated and lead a collaborative team of researchers from several different institutes in reviewing the state of the art in our understanding of interactions between the epigenome and genome. This review is currently undergoing peer review.
The results of this project have revealed that the interactions between the genome and the epigenome are important in shaping response to critical environmental stresses like heat shock. In D. melanogaster the epigenome and new TE insertions interact under heat shock, altering gene expression and developmental phenotypes. These interactions differ between populations, and the consequences can even be felt after several generations, suggesting that they could feedback into the evolutionary process if selection acted on the transgenerationally inherited phenotype. These findings push our understanding of how epigenome, genome and environment interact within individual organisms and populations. The evolutionary importance of associations between the epigenome and TEs will be further demonstrated once analysis of invasive and native D. suzukii is completed. These results will reveal whether novel epigenome-TE interactions are a factor contributing to the success of invasive species in the absence of new genetic variation.
Taken together, these results are an important part of the puzzle in explaining species responses to climate change global temperatures are rising, and heat waves and heat shocks will be encountered more frequently in the future. Our results suggest that a better understanding of the epigenomic variation and TE landscape within the genome could help to explain why some populations or species appear to do better in novel environments than others. This knowledge could have important applications for studies of invasive species and conservation of endangered ones.
Taken together, these results are an important part of the puzzle in explaining species responses to climate change global temperatures are rising, and heat waves and heat shocks will be encountered more frequently in the future. Our results suggest that a better understanding of the epigenomic variation and TE landscape within the genome could help to explain why some populations or species appear to do better in novel environments than others. This knowledge could have important applications for studies of invasive species and conservation of endangered ones.