Watson, E. T. | bioRxiv Science

bioRxiv2022

Mitochondrial effects on fertility and longevity in Tigriopus californicus contradict predictions of the mother's curse hypothesis

Strict maternal inheritance of mitochondria favors the evolutionary accumulation of sex-biased fitness effects, as mitochondrial evolution occurs exclusively in female lineages. The "mothers curse" hypothesis proposes that male-harming mutations should accumulate in mitochondrial genomes when they have neutral or beneficial effects on female fitness. Rigorous empirical tests have largely focused on Drosophila, where support for the predictions of mothers curse has been mixed. We investigated the impact of mothers curse mutations in Tigriopus californicus, a minute crustacean. Using nonrecombinant backcrosses, we introgressed four divergent mitochondrial haplotypes into two nuclear backgrounds and recorded measures of fertility and longevity. We found that the phenotypic effects of mitochondrial mutations were context-dependent, being influenced by the nuclear-background in which they were expressed, as well as the sex of the individual and rearing temperature. Mitochondrial haplotype effects were greater for fertility than longevity, and temperature effects were greater for longevity. However, in opposition to mothers curse expectations, females had higher mitochondrial genetic variance than males for fertility and longevity, little evidence of sexual antagonism favoring females was found, and the impacts of mitonuclear mismatch harmed females but not males. Together, this indicates that selection on mitochondrial variation has not resulted in the accumulation of male mutation load in Tigriopus californicus.

evolutionary biology↗

bioRxiv2022

Synaptic vesicle proteins are selectively delivered to axons in mammalian neurons

Neurotransmitter-filled synaptic vesicles (SV) mediate synaptic transmission and are a hallmark specialization in neuronal axons. Yet, how SV proteins are sorted to presynaptic nerve terminals remains the subject of debate. The leading models posit that these proteins are randomly trafficked throughout neurons and are selectively retained in presynaptic boutons. Here, we used the RUSH system, in conjunction with HaloTag labeling approaches, to study the egress of two distinct SV proteins from the soma of cultured neurons. In sharp contrast to the selective retention model, both proteins selectively and specifically entered axons and did not traffic through dendrites; only upon overexpression do SV proteins spillover into other compartments. Moreover, we observed that SV constituents were first delivered to the presynaptic plasma membrane before incorporation into SVs. These experiments reveal a new-found membrane trafficking pathway in classically polarized mammalian neurons and provide a glimpse at the first steps of SV biogenesis.

neuroscience↗