Restoration of Dendritic Complexity, Functional Connectivity, and Diversity of Regenerated Retinal Bipolar Neurons in Adult Zebrafish.

Adult zebrafish (Danio rerio) are capable of regenerating retinal neurons that have been lost due to mechanical, chemical, or light damage. In the case of chemical damage, there is evidence that visually mediated behaviors are restored after regeneration, consistent with recovery of retinal function. However, the extent to which regenerated retinal neurons attain appropriate morphologies and circuitry after such tissue-disrupting lesions has not been investigated. Adult zebrafish of both sexes were subjected to intravitreal injections of ouabain, which destroys the inner retina. After retinal regeneration, cell-selective markers, confocal microscopy, morphometrics, and electrophysiology were used to examine dendritic and axonal morphologies, connectivities, and the diversities of each, as well as retinal function, for a subpopulation of regenerated bipolar neurons (BPs). Although regenerated BPs were reduced in numbers, BP dendritic spreads, dendritic tree morphologies, and cone-bipolar connectivity patterns were restored in regenerated retinas, suggesting that regenerated BPs recover accurate input pathways from surviving cone photoreceptors. Morphological measurements of bipolar axons found that numbers and types of stratifications were also restored; however, the thickness of the inner plexiform layer and one measure of axon branching were slightly reduced after regeneration, suggesting some minor differences in the recovery of output pathways to downstream partners. Furthermore, ERG traces from regenerated retinas displayed waveforms matching those of controls, but with reduced b-wave amplitudes. These results support the hypothesis that regenerated neurons of the adult zebrafish retina are capable of restoring complex morphologies and circuitry, suggesting that complex visual functions may also be restored.SIGNIFICANCE STATEMENT Adult zebrafish generate new retinal neurons after a tissue-disrupting lesion. Existing research does not address whether regenerated neurons of adults successfully reconnect with surrounding neurons and establish complex morphologies and functions. We report that, after a chemical lesion that ablates inner retinal neurons, regenerated retinal bipolar neurons (BPs), although reduced in numbers, reconnected to undamaged cone photoreceptors with correct wiring patterns. Regenerated BPs had complex morphologies similar to those within undamaged retina and a physiological measure of photoreceptor-BP connectivity, the ERG, was restored to a normal waveform. This new understanding of neural connectivity, morphology, and physiology suggests that complex functional processing is possible within regenerated adult retina and offers a system for the future study of synaptogenesis during adult retinal regeneration.

Identifying coevolving loci using interspecific genetic correlations.

Evaluating the importance of coevolution for a wide range of evolutionary questions, such as the role parasites play in the evolution of sexual reproduction, requires that we understand the genetic basis of coevolutionary interactions. Despite its importance, little progress has been made identifying the genetic basis of coevolution, largely because we lack tools designed specifically for this purpose. Instead, coevolutionary studies are often forced to re-purpose single species techniques. Here, we propose a novel approach for identifying the genes mediating locally adapted coevolutionary interactions that relies on spatial correlations between genetic marker frequencies in the interacting species. Using individual-based multi-locus simulations, we quantify the performance of our approach across a range of coevolutionary genetic models. Our results show that when one species is strongly locally adapted to the other and a sufficient number of populations can be sampled, our approach accurately identifies functionally coupled host and parasite genes. Although not a panacea, the approach we outline here could help to focus the search for coevolving genes in a wide variety of well-studied systems for which substantial local adaptation has been demonstrated.

Identifying the molecular basis of host-parasite coevolution: merging models and mechanisms.

Mathematical models of the coevolutionary process have uncovered consequences of host-parasite interactions that go well beyond the traditional realm of the Red Queen, potentially explaining several important evolutionary transitions. However, these models also demonstrate that the specific consequences of coevolution are sensitive to the structure of the infection matrix, which is embedded in models to describe the likelihood of infection in encounters between specific host and parasite genotypes. Traditional cross-infection approaches to estimating infection matrices might be unreliable because evolutionary dynamics and experimental sampling lead to missing genotypes. Consequently, our goal is to identify the likely structure of infection matrices by synthesizing molecular mechanisms of host immune defense and parasite counterdefense with coevolutionary models. This synthesis reveals that the molecular mechanisms of immune reactions, although complex and diverse, conform to two basic models commonly used within coevolutionary theory: matching infection and targeted recognition. Our synthesis also overturns conventional wisdom, revealing that the general models are not taxonomically restricted but are applicable to plants, invertebrates, and vertebrates. Finally, our synthesis identifies several important areas for future research that should improve the explanatory power of coevolutionary models. The most important among these include empirical studies to identify the molecular hotspots of genotypic specificity and theoretical studies examining the consequences of matrices that more accurately represent multistep infection processes and quantitative defenses.

Foreign gene recruitment to the fatty acid biosynthesis pathway in diatoms.

Diatoms are highly successful marine and freshwater algae that contribute up to 20% of global carbon fixation. These species are leading candidates for biofuel production owing to ease of culturing and high fatty acid content. To assist in strain improvement and downstream applications for potential use as a biofuel, it is important to understand the evolution of lipid biosynthesis in diatoms. The evolutionary history of diatoms is however complicated by likely multiple endosymbioses involving the capture of foreign cells and horizontal gene transfer into the host genome. Using a phylogenomic approach, we assessed the evolutionary history of 12 diatom genes putatively encoding functions related to lipid biosynthesis. We found evidence of gene transfer likely from a green algal source for seven of these genes, with the remaining showing either vertical inheritance or evolutionary histories too complicated to interpret given current genome data. The functions of horizontally transferred genes encompass all aspects of lipid biosynthesis (initiation, biosynthesis, and desaturation of fatty acids) as well as fatty acid elongation, and are not restricted to plastid-targeted proteins. Our findings demonstrate that the transfer, duplication, and subfunctionalization of genes were key steps in the evolution of lipid biosynthesis in diatoms and other photosynthetic eukaryotes. This target pathway for biofuel research is highly chimeric and surprisingly, our results suggest that research done on related genes in green algae may have application to diatom models.