Biology subjects

Glastad, R. C.

Publications and source records attributed to Glastad, R. C..

2 recordsLinked to original sources

bioRxiv2025

Convergent pathways of reductive mitochondrial evolution characterised with hypercubic inference

For a striking example of mitochondrial behaviour beyond ATP generation, consider mitochondrion-related organelles (MROs). Hydrogenosomes, mitosomes, and other reduced mitochondrial forms have evolved through the loss of physical and functional features, from individual ETC complexes to oxidative phosphorylaytion and the very ability to produce ATP (and further). Reduction of mitochondria is a dramatic example of convergent evolution, occuring in every eukaryotic kingdom and many parallel times. Here, we use hypercubic inference, a class of methods from evolutionary accumulation modelling (EvAM), to explore the pathways of convergent mitochondrial reduction across eukaryotes. We find that most MRO diversity can be explained by small variations on two distinct pathways, starting with either the loss of Complex I or the loss of Complexes III/IV, which tend to proceed over different characteristic timescales. We show that different clades, including ciliates and apicomplexans, reflect particular instances of these pathways. Using metabolic modelling, we connect the structure of these evolutionary pathways to the metabolic impact of the changes involved, suggesting a plausible explanation for the dramatically convergent nature of reductive evolution. We discuss this approach in connection with related theory on the genetic and functional reduction of mitochondria across organisms.

evolutionary biology↗

bioRxiv2022

Mitochondrial network structure controls cell-to-cell mtDNA variability generated by cell divisions

Mitochondria are highly dynamic organelles, containing vital populations of mitochondrial DNA (mtDNA) distributed throughout the cell. Mitochondria form diverse physical structures in different cells, from cell-wide reticulated networks to fragmented individual organelles. These physical structures are known to influence the genetic makeup of mtDNA populations between cell divisions, but their influence on the inheritance of mtDNA at divisions remains less understood. Here, we use statistical and computational models of mtDNA content inside and outside the reticulated network to quantify how mitochondrial network structure can control the variances of inherited mtDNA copy number and mutant load. We assess the use of moment-based approximations to describe heteroplasmy variance and identify several cases where such an approach has shortcomings. We show that biased inclusion of one mtDNA type in the network can substantially increase heteroplasmy variance (acting as a genetic bottleneck), and controlled distribution of network mass and mtDNA through the cell can conversely reduce heteroplasmy variance below a binomial inheritance picture. Network structure also allows the generation of heteroplasmy variance while controlling copy number inheritance to sub-binomial levels, reconciling several observations from the experimental literature. Overall, different network structures and mtDNA arrangements within them can control the variances of key variables to suit a palette of different inheritance priorities.

genetics↗