Periodic Reporting for period 1 - MitoNuEco (The role of mitonuclear interactions in thermal and dietary adaptation)
Période du rapport: 2021-10-01 au 2023-09-30
Life depends on the energy provided by tiny cell organelles called mitochondria. Despite its importance, mitochondrial function is vulnerable as it relies on genes coded by two different genomes, the mitochondrial and the nuclear DNA. Even subtle incompatibilities between these sets of genes can be catastrophic for organisms, affecting energy production and fitness.
Our current uncertain climate is marked by more frequent shifts in temperature and food availability. All these drastic alterations are predicted to affect mitochondrial functionality. Climate change is also causing populations to migrate and overlap, raising an additional challenge for the persistence of biological communities - intergenomic compatibility. As isolated populations often diverge in mitochondrial functionality and coadapted gene combinations, genomic admixture can have severe consequences if population-specific mitochondrial and nuclear genes are incompatible. This leads me to the question: how far genomic match determines animals' adaptability to changing environments?
This project explored the dynamics of mitonuclear coevolution and the consequences these interactions bring in the context of climatic change. Specifically, I examined how the combination of genetic and ecological stressors impact organismal performance in natural fruitfly populations. Fly populations consisted in two parental lines adapted to either tropical or temperate environments, plus their reciprocal mitonuclear-decoupled cybrid lines. The combined impact of mitonuclear gene combination, sex, temperature and diet was tested at the level of mitochondrial functionality, gene expression, and organismal performance. The results of this project suggest that intergenomic interactions, coupled with thermal and dietary stress, significantly affect energy production and crucial aspects of fitness, with implications for future adaptation and persistence of insect populations.
Our current uncertain climate is marked by more frequent shifts in temperature and food availability. All these drastic alterations are predicted to affect mitochondrial functionality. Climate change is also causing populations to migrate and overlap, raising an additional challenge for the persistence of biological communities - intergenomic compatibility. As isolated populations often diverge in mitochondrial functionality and coadapted gene combinations, genomic admixture can have severe consequences if population-specific mitochondrial and nuclear genes are incompatible. This leads me to the question: how far genomic match determines animals' adaptability to changing environments?
This project explored the dynamics of mitonuclear coevolution and the consequences these interactions bring in the context of climatic change. Specifically, I examined how the combination of genetic and ecological stressors impact organismal performance in natural fruitfly populations. Fly populations consisted in two parental lines adapted to either tropical or temperate environments, plus their reciprocal mitonuclear-decoupled cybrid lines. The combined impact of mitonuclear gene combination, sex, temperature and diet was tested at the level of mitochondrial functionality, gene expression, and organismal performance. The results of this project suggest that intergenomic interactions, coupled with thermal and dietary stress, significantly affect energy production and crucial aspects of fitness, with implications for future adaptation and persistence of insect populations.
The ‘MitoNuEco’ project examined phenotypes in a total of 48 experimental groups, comprising four fly lines (coadapted and cybrid lines), two sexes, two temperatures (25°C and 29°C) and three diets (standard, high-carbohydrate and high-protein diets). Work was performed via 9 work packages (WPs). WPs 1-2 covered life-history traits characterization, including female and male fitness, development, survival, thermal tolerance, longevity and locomotor activity. Gene expression analysis was managed under WPs 3-5. WPs 6-7 focused on both mitochondrial and organismal respirometry (mitochondrial O2 and reactive oxygen species fluxes, plus CO2 efflux), and estimation of mitochondria content.
Results of the ‘MitoNuEco’ project revealed a robust phenotypic effect resulting from mitonuclear interactions. Even in absence of external stressors, cybrid lines display overall increased rates of mitochondrial respiration together with low ROS efflux compared to parental populations. This metabolic remodelling likely indicates impairment of mitochondrial function, as cybrids suffered from slower development, low fertility and reduced lifespan compared to coevolved populations. Ecological stressors also had a pervasive impact on fly performance, exacerbating mitonuclear breakdown and favouring coadapted populations. Exposure to high temperatures (29°C) negatively impacted aerobic capacity, especially in cybrids, which also experienced reduced lifespan and accelerated reproductive senescence. As for thermal stress, exposure to a carbohydrate-rich diet reduced cybrids aerobic performance, and this was accompanied by reduced larval growth but increased fecundity at young age. In a nutshell, the findings of the ‘MitoNuEco’ project indicate that intergenomic interactions play a crucial role in shaping individual phenotypes. Even subtle genetic variation can give rise to mitonuclear incompatibilities, affecting aerobic metabolism and overall fitness. Additionally, results indicate that ecological stressors have the potential to aggravate the situation, potentially influencing the ability of population to persist in a scenario of increased environmental instability.
The project has delivered two main papers, one under review for Evolution Letters (preprint doi: 10.1101/2023.09.25.559268) and another published in Bioenergetic Communications (doi: 10.26124/bec:20 23-0003). Four additional manuscripts, including a conference proceeding, are currently underway. Findings were presented at departmental meetings and international conferences, including ‘CLOE JGM’ (UCL, 06/2022), ‘CBER-CLOE’ (UCL, 12/2022), ‘Bioblast 2022’ (Innsbruck, 06/2022), ‘SEB22’ (Montpellier, 07/2022) and ‘SEB23’ (Edinburg, 07/2023). The project and its main findings have also been divulged to the general public during the ‘Pint of Science 2023’ festival (London, 05/2023) (WP 8).
Transfer of knowledge included training in life-history phenotyping, RNASeq, qPCR and respirometry approaches. Mentoring was implemented by supervising six students and serving as guest lecturer for BIOL0011 and BIOL0058 UCL courses. Communication involved promoting the project’s focal theme through social media and targeted sessions for both scientific and general audiences. This included organizing sessions at "Pint of Science” Festival and ‘SEB23’ Centenary Conference, as well as participating in the 'In2ScienceUK' 2023 program, where I exposed my research to students (WP 8). Lastly, I perfected my proposal writing skills, securing fundings from the Leverhulme Trust (R-CoI) to implement future research (WP 9).
Results of the ‘MitoNuEco’ project revealed a robust phenotypic effect resulting from mitonuclear interactions. Even in absence of external stressors, cybrid lines display overall increased rates of mitochondrial respiration together with low ROS efflux compared to parental populations. This metabolic remodelling likely indicates impairment of mitochondrial function, as cybrids suffered from slower development, low fertility and reduced lifespan compared to coevolved populations. Ecological stressors also had a pervasive impact on fly performance, exacerbating mitonuclear breakdown and favouring coadapted populations. Exposure to high temperatures (29°C) negatively impacted aerobic capacity, especially in cybrids, which also experienced reduced lifespan and accelerated reproductive senescence. As for thermal stress, exposure to a carbohydrate-rich diet reduced cybrids aerobic performance, and this was accompanied by reduced larval growth but increased fecundity at young age. In a nutshell, the findings of the ‘MitoNuEco’ project indicate that intergenomic interactions play a crucial role in shaping individual phenotypes. Even subtle genetic variation can give rise to mitonuclear incompatibilities, affecting aerobic metabolism and overall fitness. Additionally, results indicate that ecological stressors have the potential to aggravate the situation, potentially influencing the ability of population to persist in a scenario of increased environmental instability.
The project has delivered two main papers, one under review for Evolution Letters (preprint doi: 10.1101/2023.09.25.559268) and another published in Bioenergetic Communications (doi: 10.26124/bec:20 23-0003). Four additional manuscripts, including a conference proceeding, are currently underway. Findings were presented at departmental meetings and international conferences, including ‘CLOE JGM’ (UCL, 06/2022), ‘CBER-CLOE’ (UCL, 12/2022), ‘Bioblast 2022’ (Innsbruck, 06/2022), ‘SEB22’ (Montpellier, 07/2022) and ‘SEB23’ (Edinburg, 07/2023). The project and its main findings have also been divulged to the general public during the ‘Pint of Science 2023’ festival (London, 05/2023) (WP 8).
Transfer of knowledge included training in life-history phenotyping, RNASeq, qPCR and respirometry approaches. Mentoring was implemented by supervising six students and serving as guest lecturer for BIOL0011 and BIOL0058 UCL courses. Communication involved promoting the project’s focal theme through social media and targeted sessions for both scientific and general audiences. This included organizing sessions at "Pint of Science” Festival and ‘SEB23’ Centenary Conference, as well as participating in the 'In2ScienceUK' 2023 program, where I exposed my research to students (WP 8). Lastly, I perfected my proposal writing skills, securing fundings from the Leverhulme Trust (R-CoI) to implement future research (WP 9).
Despite increasing evidence that mitochondrial genes evolution can be shaped by natural selection, few studies have explored the adaptive value of mitochondrial variation in conjunct with variation in interacting nuclear genes. As a result, the realistic contribution of intergenomic interactions to population dynamics is largely unknown. This research project aimed to fill that gap and is unprecedented in its field for two main reasons. First, it integrates both genetic and environmental factors, as well as expertise in physiology, transcriptomics, biochemistry and evolutionary biology to provide the most in-depth analysis of the dynamics of mitonuclear coevolution. Second, it examines fly populations that naturally coexist and hybridize in the wild, adding crucial real-world relevance to its outcome. The findings of this research are of interest to diverse academic constituencies. From cell biologists interested in mitochondrial function to evolutionary biologists investigating intergenomic coevolution. Results highlighted the importance of integrating genetic, thermal and nutritional data to better predict species distribution, and should therefore be of major interest to ecological biologists interested in species adaptation and conservation. Beyond basic research, applied areas that could benefit from this results are the biomedical and the agricultural fields, where mitonuclear incompatibilities have been investigated in the context of mitochondrial disorders, interventions such as mitochondrial replacement therapy, and animal breeding. Finally, the worldwide decline of insect populations is severely impacting trophic networks and crop pollination, with downstream impact on human economy and nutrition. Understanding whether mitonuclear interactions might be part of this decline is therefore of major interest not only to the scientific community, but also the general public.