All eukaryotes have or once had mitochondria. These organelles are the remains of an ancient symbiosis with a bacterium early in eukaryotic evolution some 2 billion years ago. As such, mitochondria retain their own genome (mtDNA). Although it only encodes a small fraction of the genes encoded by nuclear DNA (nucDNA), its products must interact closely with their nucDNA-encoded counterparts in order to generate the energy needed for maintaining eukaryotic cellular functions. Mutations in mtDNA can lead to a breakdown in this interaction, with dire consequences for organismal health. Mutations in mtDNA accumulate rapidly compared to nucDNA in animals, and one general theory of ageing posits that the accumulation of somatic mtDNA mutations leads to ageing and the onset of age-related diseases. However, not all eukaryotes have elevated mtDNA mutation rates. To understand how underlying mtDNA mutations influence organismal health and fitness, the proposed research will examine mito-nuclear mismatch in the plant genus Silene, which occurs when mtDNA from one population/species is expressed against the nuclear background of a distant relative. Silene contains species with both slowly and rapidly evolving mtDNA, making it an ideal model for this research. The overarching question addressed by the proposed research is to determine how mito-nuclear interactions influence organismal physiology, ecology, and evolution. Silene species and populations with varying degrees of evolutionary relatedness will be crossed in order to produce progeny with a range of predicted mito-nuclear mismatch severities. Standard growth phenotypes, metabolic rates, and fecundities will be assayed in these hybrids. Oxidative phosphorylation (OXPHOS) proficiency will be assessed in both control and mismatched individuals by assessing OXPHOS complex II and IV activity. Complex IV consists of both mtDNA and nucDNA-ecoded subunits and should show reduced activity in mismatched individuals, while complex II serves as a negative control, since it is composed solely of nucDNA-encoded subunits. Furthermore, differential gene expression will be assessed between a subset of control and mismatched individuals via RNA-Seq to test between several alternative hypotheses for how mismatch affects organismal function. Finally, control and mismatched individuals will be assessed under variable drought regimes to determine if specific mito-nuclear backgrounds may be adapted to particular environments. This work will extend our understanding of mito-nuclear genomic interactions by utilizing a well- suited model that complements previous studies. Its results will be relevant to ongoing issues in human health including advancing theories of ageing and commenting on ongoing debates regarding the long-term consequences of mitochondrial replacement therapy (aka, three-parent in-vitro fertilization).

Public Health Relevance

All animal and plant cells have a smaller mitochondrial genome in addition to the larger genome located in the nucleus. The products of these two genomes must work together in an intricate, complex way in order to meet the energy needs of the cell and maintain the health and fitness of the organism. Therefore, by examining how incongruity between these two genomes influences energy production and gene expression in eukaryotes, this research will provide insights into human health.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Postdoctoral Individual National Research Service Award (F32)
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Maas, Stefan
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Colorado State University-Fort Collins
Schools of Arts and Sciences
Fort Collins
United States
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Sloan, Daniel B; Havird, Justin C; Sharbrough, Joel (2017) The on-again, off-again relationship between mitochondrial genomes and species boundaries. Mol Ecol 26:2212-2236
Havird, Justin C; Trapp, Paul; Miller, Christopher M et al. (2017) Causes and Consequences of Rapidly Evolving mtDNA in a Plant Lineage. Genome Biol Evol 9:323-336
Havird, Justin C; Sloan, Daniel B (2016) The Roles of Mutation, Selection, and Expression in Determining Relative Rates of Evolution in Mitochondrial versus Nuclear Genomes. Mol Biol Evol 33:3042-3053
Havird, Justin C; Fitzpatrick, Sarah W; Kronenberger, John et al. (2016) Sex, Mitochondria, and Genetic Rescue. Trends Ecol Evol 31:96-99
Havird, Justin C; Santos, Scott R (2016) Developmental Transcriptomics of the Hawaiian Anchialine Shrimp Halocaridina rubra Holthuis, 1963 (Crustacea: Atyidae). Integr Comp Biol 56:1170-1182
Havird, Justin C; Mitchell, Reed T; Henry, Raymond P et al. (2016) Salinity-induced changes in gene expression from anterior and posterior gills of Callinectes sapidus (Crustacea: Portunidae) with implications for crustacean ecological genomics. Comp Biochem Physiol Part D Genomics Proteomics 19:34-44
Havird, Justin C; Santos, Scott R (2016) Here We Are, But Where Do We Go? A Systematic Review of Crustacean Transcriptomic Studies from 2014-2015. Integr Comp Biol 56:1055-1066
Rockenbach, Kate; Havird, Justin C; Monroe, J Grey et al. (2016) Positive Selection in Rapidly Evolving Plastid-Nuclear Enzyme Complexes. Genetics 204:1507-1522
Sloan, Daniel B; Fields, Peter D; Havird, Justin C (2015) Mitonuclear linkage disequilibrium in human populations. Proc Biol Sci 282:
Havird, Justin C; Whitehill, Nicholas S; Snow, Christopher D et al. (2015) Conservative and compensatory evolution in oxidative phosphorylation complexes of angiosperms with highly divergent rates of mitochondrial genome evolution. Evolution 69:3069-81

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