No abstract

To address questions about mechanisms of filament-based organelle transport, a system was developed to image and track mitochondria in an intact Drosophila nervous system. Mutant analyses suggest that the primary motors for mitochondrial movement in larval motor axons are kinesin-1 (anterograde) and cytoplasmic dynein (retrograde), and interestingly that kinesin-1 is critical for retrograde transport by dynein. During transport, there was little evidence that force production by the two opposing motors was competitive, suggesting a mechanism for alternate coordination. Tests of the possible coordination factor P150 Glued suggested that it indeed influenced both motors on axonal mitochondria, but there was no evidence that its function was critical for the motor coordination mechanism. Observation of organelle-filled axonal swellings ("organelle jams" or "clogs") caused by kinesin and dynein mutations showed that mitochondria could move vigorously within and pass through them, indicating that they were not the simple steric transport blockades suggested previously. We speculate that axonal swellings may instead reflect sites of autophagocytosis of senescent mitochondria that are stranded in axons by retrograde transport failure; a protective process aimed at suppressing cell death signals and neurodegeneration. INTRODUCTIONOrganelle transport is central to the organization, developmental fate, and functions of asymmetric cells. A bipolar neuron is an extreme case, with the somato-dendritic region and the axon containing different sets of proteins and organelles. In general, much of the machinery for synthesizing and recycling neuronal components is clustered near the nucleus. Because an axon, often with an axial ratio of many thousands, usually contains Ͼ99% of the neuronal cytoplasm, active transport of new components away from the cell body and of spent components and trophic materials back toward the cell body is critical. Disruptions of axonal transport are thought to contribute to the pathologies of Alzheimer's, amyotrophic lateral sclerosis, and other neurodegenerative diseases (reviewed by Mandelkow and Mandelkow, 2002;Hirokawa and Takemura, 2005).Long-distance organelle transport in axons is driven by motor proteins that move along parallel microtubules whose plus ends are mostly oriented toward the axon terminal (reviewed by Hollenbeck and Saxton, 2005). There are multiple types of microtubule motors in postmitotic vertebrate neurons, including kinesins that can move toward either plus-or minus-ends and at least one cytoplasmic dynein that moves toward minus-ends (Martin et al., 1999b;Hirokawa and Takemura, 2005;Hollenbeck and Saxton, 2005). Which motors bind and move which axonal components? When multiple types of motors bind a single cargo, do they collaborate or compete, how are they regulated, and how do their combined activities generate an optimal distribution of that type of cargo?Axonal mitochondria are critical for the physiology of neurons and are particularly well suited for studying active tr...

Most organisms reproduce through outcrossing, even though it comes with significant costs. The Red Queen hypothesis proposes that selection from coevolving pathogens facilitates the persistence of outcrossing in spite of these costs. We utilized experimental coevolution to test the Red Queen hypothesis, and found that coevolution with a bacterial pathogen (Serratia marcescens) resulted in significantly more outcrossing in mixed mating experimental populations of the nematode Caenorhabditis elegans. Furthermore, we found that coevolution with the pathogen rapidly drove obligately selfing populations to extinction, while outcrossing populations persisted through reciprocal coevolution. Thus, consistent with the Red Queen hypothesis, coevolving pathogens can select for biparental sex.

According to the Red Queen hypothesis--which states that interactions among species (such as hosts and parasites) lead to constant natural selection for adaptation and counter-adaptation--the disproportionate evolutionary success of parasites on common host genotypes leads to correlated selection for sexual reproduction and local adaptation by the parasite population. Here we determined whether local adaptation is due to disproportionate infection of common host genotypes, and, if so, whether infection of common host genotypes is due to commonness per se, or some other aspect of these genotypes. In a reciprocal cross-inoculation experiment parasites occupying the same geographical area (sympatric) infected locally common host genotypes significantly more often than rare host genotypes, whereas parasites occupying separate geographical areas (allopatric) showed no such significant difference. A mixed source of parasites (containing F1 hybrids) also showed no difference in infection between rare and common host genotypes. These results show that local adaptation results from parasite tracking of locally common host genotypes, and, as such, a necessary condition of the Red Queen hypothesis is met.

No abstract

The geographic mosaic theory of coevolution is predicated on structured populations of interacting species where gene flow and the force of selection can vary among populations, leading to a mosaic of traits in space. Here, I briefly review some recent studies of adaptation by a sterilizing parasite to structured populations of a freshwater snail. The results show geographic structure as expected under the geographic mosaic model. I then consider the effects of virulence and migration on local adaptation by parasites using a computer simulation. The results suggest that high virulence and low migration contribute to the strength of local adaptation by parasites. Highly virulent parasites showed adaptation to local hosts for migration rates of up to 10% of the population per generation. In addition, because of the dynamic nature of host-parasite coevolution, the magnitude of local adaptation fluctuates over time. During some points in the cycle, parasites may be no more effective at infecting individuals from local host populations, even though they would be shown to be locally adapted if examined over enough generations. Contrary to expectation, parasite local adaptation was not affected by giving the parasite a longer generation time than the host, but differences in local selection intensities had a dramatic effect.

Two classes of models attempt to explain why obligate partheno-genesis only rarely replaces sexual reproduction in natural populations, in spite of the apparent reproductive advantage that parthenogens gain by producing only female offspring. The mutation-accumulation models suggest that sex is adaptive because it purges the genome of harmful recurrent mutations. The ecological genetic models postulate that sex is adaptive in variable environments, particularly when the relevant variation is generated by coevolutionary interactions with parasites. Both of these models have considerable merit, but would seem to have limitations. The mutation-accumulation models require high rates of mutation; the coevolutionary models require that parasites have severe fitness effects on their hosts. In addition, parasites could select for clonal diversity and thereby erode any advantage that sex gains by producing variable progeny. Here we consider the interaction between mutation accumulation and host-parasite coevolution. The results suggest that even moderate effects by parasites combined with reasonable rates of mutation could render sex evolutionarily stable against repeated invasion by clones.

Understanding the source and diversity of clones is necessary to resolve the complicated issues surrounding the apparent evolutionary stability of sexual reproduction. The source of clones is important because present theory is based on an "all else equal" assumption, which is predicated on the idea that clonal mutants are derived from and compete with local sexual populations.Clonal diversity is important because it reduces the advantage of sexual reproduction under either soft selection (the Tangled Bank Hypothesis) or under strict frequency-dependent selection (the Red Queen Hypothesis).In the present study, protein electrophoresis was used to determine the source and diversity of clones in a freshwater snail (Potamopyrgus antipodarum) in four glacial lakes in which sexual and clonal females were thought to coexist. The results showed (1) that the populations were mixtures of diploid sexual and triploid asexual individuals, (2) that genotypic diversity of clonal populations is very high in all four lakes (but lower than in the sympatric sexual populations), and (3) that the clones are polyphyletically derived from their sympatric sexual populations. Consequently, repeated mutation to parthenogenetic reproduction since the Pleistocene has introduced a different and diverse set of clones in all four lakes. Such diversity may provide a challenge for the ecological theories of sex that rely on frequency-dependent selection.