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The evolutionary and ecological implications of mito-nuclear epistasis

Periodic Reporting for period 1 - MITONUC (The evolutionary and ecological implications of mito-nuclear epistasis)

Reporting period: 2015-10-01 to 2017-09-30

Our understanding of the evolutionary significance of mtDNA is currently being revised. The traditional view that sequence variation found within the mitochondrial genome is selectively neutral is being displaced by a growing body of evidence for selection on mitochondrial genes from a variety of empirical domains. The MITONUC project added a novel and critical piece to our understanding of mtDNA evolution by (i) assessing environmental- and sex-specificity of mito-nuclear phenotypic effects and by (ii) experimentally demonstrating that selection acts upon mtDNA and, perhaps most importantly, by testing whether negative frequency dependent selection acts to maintain non-neutral mitochondrial genetic variation.
Thus, this research project is very timely indeed and contains several important novel elements.

(1) The importance of improving our understanding of the maintenance of genetic diversity cannot be overemphasized and the scientific implications of a shifting view of mtDNA are multifaceted and equally consequential: every year, some 4500 scientific papers rely directly upon mtDNA data.

(2) The MITONUC results represents has an important and novel addition to fundamental importance of the mito-nuclear epistatic interactions.

(3) The MITONUC project document multivariate phenotypic effects of mito-nuclear epistatic interactions in order to fully understand selection on mitonuclear genotypes.The main findings showed no significance of genetic effect (nuclear and mitochondrial) and there interaction so we can conclude that mito-nuclear epistasis seems to be no responsible for the shape of reaction norms. However, we have detect a significant environmental effect (food and temperature) which suggest parental effect on phenotypic variation in offspring. The recent integration of epigenetics into developmental psychobiology illustrates the processes by which environmental conditions in early life structurally alter DNA, providing a physical basis for the influence of the perinatal environmental signals on phenotype over the life of the individual.

(4) The crucial project result is novel experimental proof that t balancing selection acts to maintain mitochondrial DNA variation within populations of Drosophila subosbcura. We experimentally confirmed that starting frequencies in population cages were changed from 20:80 and 80:20 to almost equal (50:50) which is unique experimental proof that mtDNA variability in population has adaptive response and that is maintained by negative frequency dependent selection (NFDS). Second, there is a significant interaction between starting frequencies and environment on the strength for NFDS, but it is weaker in the heterogeneous environment when mitochondrial haplotype I is started as common in population.

This research will have a range of biological implications, ranging from applied medical genetics over our use of mitochondrial genetic markers in population genetics/biology to speciation and our understanding of thermal adaptation to climate change.
WP 1: Phenotypic effects of different temperature (19°C and 22°C) and food regimes (3 yeast concentration in food medium) on fitness performance (viability, developmental time, sex ratio, wing size and shape), and metabolic efficiency in mito-nuclear lines of Drosophila subobscura

WP 2: Negative frequency dependent selection on sympatric mtDNA haplotypes in Drosophila subobscura

WP 3: Publishing papers, conference participation and results dissemination

Published papers
1. Arnqvist G., Kurbalija Novicic Z., Castro J.A. and Sayadi A. (2016). Negative frequency dependent selection on sympatric mtDNA haplotypes in Drosophila subobscura. Hereditas, 153: 15. doi: 10.1186/s41065-016-0020-2
2. Pertoldi C., Bahrndorff S., Kurbalija Novicic Z. and Rohde P.D. (2016). The Novel Concept of “Behavioural Instability” and Its Potential Applications. Symmetry, 8, 135; doi:10.3390/sym8110135

3. Tanaskovic M., Kurbalija Novicic Z., Kenig B., Savic Veselinovic M., Stamenkovic-Radak M., Andjelkovic M. (2016). Synergistic effect of environmental and genomic stress on wing size of Drosophila suboscura. Genetika-Belgrade, (2016), vol. 48 br. 3, str. 1039-1052

1. Kurbalija Novicic Z., Jelic M. and Arnqvist G. Parental effect of environmental stress (temperature and food experimental treatment) and the evaluation of significance of both, nuclear and mitochondrial genetic background and their possible interaction in Drosophila subosbcura mitonuclear introgression lines. In prep.
2. Kurbalija Novicic Z., Sayadi A. and Arnqvist A. Negative frequency dependent selection on sympatric mtDNA haplotypes in Drosophila subobscura. In prep.
3. Kurbalija Novicic Z., Boden R., Bajic K., Cunningham J. Metabolic efficiency of mitonuclear introgression lines of Drosophila subobscura after acute exposure to lithium. In prep.
4. Snook R., Kurbalija Novicic Z., Arnqvist G. Metabolic rate in monogamy and polygamy selected lines of Drosophila pseudoobscura. In prep.

Conferences and meetings

The Congress of the European Society for Evolutionary Biology- Groningen, Netherlands (20-25 August 2017)

Kurbalija Novicic Z., Arnqvist G. The evolutionary and ecological significance of mitonuclear epistasis. P19, poster session S15

Revolution meeting- Evolutionary Biology center, Uppsala University, Sweden (Feb 2016)
Kurbalija Novicic Z. Habitat driven selection in sympatric populations of Drosophila subobscura. Talk

WP 4: Outreach activity for general public
The results of the proposed project were communicated to general public through popular media (Facebook, Instagram etc.), printed media, internet portals and TV programs.
I had active participation in project- Researchers Night ReFocuS 2016/2017 (H2020-MSCA-NIGHT-2016/2017-722341) as a member of Advisory Board.

WP 5: Project management, Risk management and reporting
The implementation of the project were fulfilled according to the Personal Career Development Plan which were established between the researcher fellow (Zorana Kurbalija Novicic) and the supervisor (Göran Arnqvist) during the first two weeks of the project.
The project progress were monitored though the following measures:

-Regular) meetings between the research fellow and the supervisor for short-term planning of activity schedules
- Continuous and periodic report to EU Commission. The final report to EU Commission is provided within 60 days after project ending.
MITONUC project bridging the gap between basic science knowledge and science application. The project results will be implemented in human medicine in the field of neurobiology and psychiatry. Thus, future efforts will develop novel approach to limited understanding of the underlining neurobiology of psychiatric disorders. All of this contributes to difficulties to develop a strong biological platform underling the possibilities to define the biological gold-standard diagnostics for different mental disorders.
The future project has interdisciplinary character bringing together the field of population genetics with a special focus on significance of mDNA variability and mito-nuclear interactions and the field of clinical psychiatry (Department for Neuroscience, Psychiatry, University of Uppsala). In addition, the project will have benefits from established bio-bank infrastructure (Uppsala Psychiatric Patient Samples- UPP).
Drospohila subobscura
Researchers Night 2016 (Belgrade, Serbia)