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The brain performs various cognitive functions by learning the spatiotemporal salient features of the environment. This learning requires unsupervised segmentation of hierarchically organized spike sequences, but the underlying neural mechanism is only poorly understood. Here, we show that a recurrent gated network of neurons with dendrites can efficiently solve difficult segmentation tasks. In this model, multiplicative recurrent connections learn a context-dependent gating of dendro-somatic information transfers to minimize error in the prediction of somatic responses by the dendrites. Consequently, these connections filter the redundant input features represented by the dendrites but unnecessary in the given context. The model was tested on both synthetic and real neural data. In particular, the model was successful for segmenting multiple cell assemblies repeating in large-scale calcium imaging data containing thousands of cortical neurons. Our results suggest that recurrent gating of dendro-somatic signal transfers is crucial for cortical learning of context-dependent segmentation tasks.

Abstract Certain mycophagous Drosophila species are the only known eukaryotes that can tolerate some highly potent mycotoxins. This association between mycophagy and mycotoxin tolerance is well established because Drosophila species that switch hosts from mushrooms to other food sources lose their mycotoxin tolerance trait without any evolutionary lag. These findings suggest that mycotoxin tolerance may be a costly trait to maintain. In this study, we attempted to identify whether mycotoxin tolerance has a fitness cost. Larval competitive ability is a vital fitness trait, especially in holometabolous insects, where the larvae cannot move to a new host. Furthermore, larval competitive ability is known to be associated with many critical life-history traits. Here we studied whether mycotoxin tolerance adversely affects larval competitive ability on isofemale lines from 2 distinct locations. We observed that the extent of mycotoxin tolerance affected larval competitive ability, but only in isofemale lines from one location. Additionally, we observed that the high mycotoxin-tolerant isofemale lines from the same location showed poor survival to eclosion. This study shows that mycotoxin tolerance is associated with fitness costs and provides preliminary evidence of an association between local adaptation and mycotoxin tolerance.

Changes in the control of developmental gene expression patterns have been implicated in the evolution of animal morphology. However, the genetic mechanisms underlying complex morphological traits remain largely unknown. Here we investigated the molecular mechanisms that induce the pigmentation gene yellow in a complex color pattern on the abdomen of Drosophila guttifera . We show that at least five developmental genes may collectively activate one cis -regulatory module of yellow in distinct spot rows and a dark shade to assemble the complete abdominal pigment pattern of Drosophila guttifera . One of these genes, wingless , may play a conserved role in the early phase of spot pattern development in several species of the quinaria group. Our findings shed light on the evolution of complex animal color patterns through modular changes of gene expression patterns.

Codon usage bias, where certain codons are used more frequently than their synonymous counterparts, is an interesting phenomenon influenced by three evolutionary forces: mutation, selection, and genetic drift. To better understand how these evolutionary forces affect codon usage bias, an extensive study to detect how codon usage patterns change across species is required. This study investigated 668 single-copy orthologous genes independently in 29 Drosophila species to determine how the codon usage patterns change with phylogenetic distance. We found a strong correlation between phylogenetic distance and codon usage bias and observed striking differences in codon preferences between the two subgenera Drosophila and Sophophora. As compared to the subgenus Sophophora, species of the subgenus Drosophila showed reduced codon usage bias and a reduced preference specifically for codons ending with C, except for codons with G in the second position. We found that codon usage patterns in all species were influenced by the nucleotides in the codon’s 2nd and 3rd positions rather than the biochemical properties of the amino acids encoded. We detected a concordance between preferred codons and preferred dinucleotides (at positions 2 and 3 of codons). Furthermore, we observed an association between speciation, codon preferences, and dinucleotide preferences. Our study provides the foundation to understand how selection acts on dinucleotides to influence codon usage bias.

Abstract Intra-specific genomic diversity is well documented in microbes. The question, however, remains whether natural selection or neutral evolution is the major contributor to this diversity. We undertook this study to estimate genomic diversity in Pseudoalteromonas atlantica populations and whether the diversity, if present, could be attributed to environmental factors or distance effects. We isolated and sequenced twenty-three strains of P. atlantica from three geographically distant deep marine basins and performed comparative genomic analyses to study the genomic diversity of populations among these basins. Average nucleotide identity followed a strictly geographical pattern. In two out of three locations, the strains within the location exhibited >99.5% identity, whereas, among locations, the strains showed <98.11% identity. Phylogenetic and pan-genome analysis also reflected the biogeographical separation of the strains. Strains from the same location shared many accessory genes and clustered closely on the phylogenetic tree. Phenotypic diversity between populations was studied in ten out of twenty-three strains testing carbon and nitrogen source utilization and osmotolerance. A genetic basis for phenotypic diversity could be established in most cases but was apparently not influenced by local environmental conditions. Our study suggests that neutral evolution may have a substantial role in the biodiversity of P. atlantica. Genotype and phenotype of globally distributed bacteria vary by marine basins.

Many mycophagous Drosophila species have adapted to tolerate high concentrations of mycotoxins, an ability not reported in any other eukaryotes. Although an association between mycophagy and mycotoxin tolerance has been established in many Drosophila species, the genetic mechanisms of the tolerance are unknown. This study presents the inter‐ and intraspecific variation in the mycotoxin tolerance trait. We studied the mycotoxin tolerance in four Drosophila species from four separate clades within the immigrans‐tripunctata radiation from two distinct locations. The effect of mycotoxin treatment on 20 isofemale lines per species was studied using seven gross phenotypes: survival to pupation, survival to eclosion, development time to pupation and eclosion, thorax length, fecundity, and longevity. We observed interspecific variation among four species, with D. falleni being the most tolerant, followed by D. recens, D. neotestacea, and D. tripunctata, in that order. The results also revealed geographical variation and intraspecific genetic variation in mycotoxin tolerance. This report provides the foundation for further delineating the genetic mechanisms of the mycotoxin tolerance trait. Many mycophagous Drosophila species have adapted to tolerate high concentrations of mycotoxins, an ability not reported in any other eukaryotes. We observed interspecific variation among four species, with D. falleni being the most tolerant, followed by D. recens, D. neotestacea, and D. tripunctata, in that order. We further observed fitness effects of the mycotoxin tolerance in two species: D. tripunctata and D. neotestacea.

Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia (AML) characterized by the presence of t(15;17)(q22;q21) translocation leading to fusion between PML and RARa gene. Treatment combining all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has dramatically improved the prognosis of APL. We report a rare finding of primary clone of t(15;17) followed by a sequential clonal evolution of additional derivative chromosome 6 formation by a two hit mechanism. Our case showed a good clinical response with a four years and nine months event free survival after ATRA and ATO combination therapy in spite of existence of three chromosomal abnormalities stating that targeted therapy overcomes the adverse effects of additional genetic markers. However, close monitoring with assessment for long term prognostic behavior is required.

Changes in the control of developmental gene expression patterns have been implicated in the evolution of animal morphology. However, the genetic mechanisms underlying complex morphological traits remain largely unknown. Here we investigated the molecular mechanisms that induce the pigmentation gene yellow in a complex color pattern on the abdomen of Drosophila guttifera. We show that at least five developmental genes may collectively activate one cis-regulatory module of yellow in distinct spot rows and a dark shade to assemble the complete abdominal pigment pattern of Drosophila guttifera. One of these genes, wingless, may play a conserved role in the early phase of spot pattern development in several species of the quinaria group. Our findings shed light on the evolution of complex animal color patterns through modular changes of gene expression patterns.

Organisms with novel adaptive traits are excellent research subjects for evolutionary biologists. The trajectory of an adaptive trait, how it arose, what evolutionary forces acted on the trait, and fitness effects of the trait, provide insights in understanding how the trait influences biodiversity in the organisms carrying the trait. One such trait is mycotoxin tolerance.Many mycophagous Drosophila species from the immigrans-tripunctata radiation have adapted to tolerate high concentrations of mycotoxins, an ability not reported in any other eukaryotes. Although an association between mycophagy and mycotoxin tolerance has been established in many Drosophila species, the genetic mechanisms of the tolerance are unknown . In the second chapter of this dissertation, I attempt to understand the genetic architecture of the mycotoxin tolerance trait. I studied the mycotoxin tolerance in four Drosophila species from four separate clades within the immigrans-tripunctata radiation from two distinct locations : Escanaba and Great Smoky Mountains. I observed interspecific variation among four species, with D. falleni being the most tolerant to mycotoxins, followed by D. recens, D. neotestacea, and D. tripunctata, in that order. I observed quantitative genetic variation, indicating that mycotoxin tolerance is a complex trait.The second chapter provides the foundation for further delineating the genetic mechanisms of the mycotoxin tolerance trait. It has been hypothesized that mycotoxin tolerance is costly because Drosophila species that switch hosts from mushrooms to other food sources lose this trait without any evolutionary lag. In the second chapter, I observed fitness effects of the mycotoxin tolerance trait in two species: D. tripunctata and D. neotestacea.In the third chapter, I attempted to identify whether mycotoxin tolerance has a fitness cost, adversely affecting larval competitive ability. I observed that the extent of mycotoxin tolerance did not affect larval competitive ability. Chapters 2 and 3 also help to shed light on another evolutionary aspect of mycotoxin tolerance , local adaptation. I observed geographic variation in mycotoxin tolerance, suggesting the influence of local adaptation on the mycotoxin tolerance trait.In chapter 4, I have analyzed 29 Drosophila genomes to identify the codon usage bias between two subgenera: Sophophora and Drosophila. I found a strong correlation between phylogenetic distance and codon usage bias and observed striking differences in codon preferences between the subgenera Drosophila and Sophophora. Compared to the subgenus Sophophora, species of the subgenus Drosophila showed reduced codon usage bias and a reduced preference specifically for codons ending with C, except for codons with G in the second position. I found that codon usage patterns in all species were influenced by the nucleotides in the codons’ 2nd and 3rd positions rather than the biochemical properties of the amino acids encoded. I detected a concordance between preferred codons and preferred dinucleotides (at positions 2 and 3 of codons). Furthermore, I observed an association between speciation, codon preferences, and dinucleotide preferences. This study provides the foundation to understand how selection acts on dinucleotides to influence codon usage bias.