DNA methylation and DNA methyltransferases

The prevailing views as to the form, function, and regulation of genomic methylation patterns have their origin many years in the past, at a time when the structure of the mammalian genome was only dimly perceived, when the number of protein-encoding mammalian genes was believed to be at least five times greater than the actual number, and when it was not understood that only ~10% of the genome is under selective pressure and likely to have biological function. We use more recent findings from genome biology and whole-genome methylation profiling to provide a reappraisal of the shape of genomic methylation patterns and the nature of the changes that they undergo during gametogenesis and early development. We observe that the sequences that undergo deep changes in methylation status during early development are largely sequences without regulatory function. We also discuss recent findings that begin to explain the remarkable fidelity of maintenance methylation. Rather than a general overview of DNA methylation in mammals (which has been the subject of many reviews), we present a new analysis of the distribution of methylated CpG dinucleotides across the multiple sequence compartments that make up the mammalian genome, and we offer an updated interpretation of the nature of the changes in methylation patterns that occur in germ cells and early embryos. We discuss the cues that might designate specific sequences for demethylation or de novo methylation during development, and we summarize recent findings on mechanisms that maintain methylation patterns in mammalian genomes. We also describe the several human disorders, each very different from the other, that are caused by mutations in DNA methyltransferase genes

Toward Cultural Oncology: The Evolutionary Information Dynamics of Cancer

'Racial' disparities among cancers, particularly of the breast and prostate, are something of a mystery. For the US, in the face of slavery and its sequelae, centuries of interbreeding have greatly leavened genetic differences between 'Blacks' and 'whites', but marked contrasts in disease prevalence and progression persist. 'Adjustment' for socioeconomic status and lifestyle, while statistically accounting for much of the variance in breast cancer, only begs the question of ultimate causality. Here we propose a more basic biological explanation that extends the theory of immune cognition to include elaborate tumor control mechanisms constituting the principal selection pressure acting on pathologically mutating cell clones. The interplay between them occurs in the context of an embedding, highly structured, system of culturally specific psychosocial stress which we find is able to literally write an image of itself onto disease progression. The dynamics are analogous to punctuated equilibrium in simple evolutionary proces

Remembering the future: An overview of co-evolution in musical improvisation

Musical improvisation is driven mainly by the unconscious mind, engaging the dialogic imagination to reference the entire cultural heritage of an improvisor in a single flash. This paper introduces a case study of evolutionary computation techniques, in particular genetic co-evolution, as applied to the frequency domain using MPEG7 techniques, in order to create an artificial agent that mediates between an improvisor and her unconscious mind, to probe and unblock improvisatory action in live music performance or practice

Natural selection favoring more transmissible HIV detected in United States molecular transmission network.

HIV molecular epidemiology can identify clusters of individuals with elevated rates of HIV transmission. These variable transmission rates are primarily driven by host risk behavior; however, the effect of viral traits on variable transmission rates is poorly understood. Viral load, the concentration of HIV in blood, is a heritable viral trait that influences HIV infectiousness and disease progression. Here, we reconstruct HIV genetic transmission clusters using data from the United States National HIV Surveillance System and report that viruses in clusters, inferred to be frequently transmitted, have higher viral loads at diagnosis. Further, viral load is higher in people in larger clusters and with increased network connectivity, suggesting that HIV in the United States is experiencing natural selection to be more infectious and virulent. We also observe a concurrent increase in viral load at diagnosis over the last decade. This evolutionary trajectory may be slowed by prevention strategies prioritized toward rapidly growing transmission clusters

Application of Evolutionary Network Concept in Structuring Mathematics Curriculum

Phylogenetic tree and in general, evolutionary network, has found its application well beyond the biological fields and has even percolated into recent high demanding areas, such as data mining and social media chain reactions. An extensive survey of its current applications are presented here. An attempt has been made to apply the very concept in the mathematics course curriculum inside a degree program. Various features of the tree structure are identified within the curriculum network. To highlight various key components and to enhance the visual effect, several diagrams are presented. The combined effect of these diagram provides a sense of the entire curriculum tree structure. The current study can be used as a potential tool for effective student advisement, student placement within the curriculum, efficient resource allocation, etc. Future work may encompass detailing and implementing these applications

A Developmental Organization for Robot Behavior

This paper focuses on exploring how learning and development can be structured in synthetic (robot) systems. We present a developmental assembler for constructing reusable and temporally extended actions in a sequence. The discussion adopts the traditions of dynamic pattern theory in which behavior is an artifact of coupled dynamical systems with a number of controllable degrees of freedom. In our model, the events that delineate control decisions are derived from the pattern of (dis)equilibria on a working subset of sensorimotor policies. We show how this architecture can be used to accomplish sequential knowledge gathering and representation tasks and provide examples of the kind of developmental milestones that this approach has already produced in our lab

The transmitted HIV-1 subtype C: characterization of the transmitted/founder full-length virus genome and the influence of early immune selective pressure on virus replication

Includes bibliographical references.The identification of targets of early immune responses associated with control of HIV-1 infection will inform immunogen design for vaccine interventions. The early evolution of transmitted/founder subtype C virus sequences was investigated to determine the location and frequency of immune selection, and the impact of early immune escape mutations on viral replicative capacity. Single-genome amplified env sequences from 26 acutely-infected women were evaluated for conformance to a model of random evolution to elucidate multiplicity of infection. Near fulllength genome sequences from the first six months of infection were generated for five women and sites evolving under immune selection were mapped. CD8+ cytotoxic Tlymphocyte escape mutations in HLA-B-restricted epitopes were introduced into infectious molecular clones of cognate transmitted/founder viruses by site-directed mutagenesis and their impact on viral replicative fitness was evaluated using parallel replication assays. In 77% of women (n=20) a single transmitted/founder variant established infection and two to five variants in the remaining 23% (n=6). Near full-length genome sequencing in five women confirmed single variant/low-diversity transmission and identified fifty-five genome regions evolving under immune selection, 40% of which was attributed to CD8+ cytotoxic Tlymphocyte pressure, 35% to antibody-mediated pressure, 16% to reversion and 9% could not be classified. The rate of sequence diversification and number of sites evolving under immune selection was highest in nef. The majority of evolving CD8+ cytotoxic T-lymphocyte epitopes (82%) contained shuffling/toggling mutations. A novel B*15:10-associated mutation, A164T, combined with a V85A Pol mutation reduced viral replication capacity in one individual. In a second individual, the attenuating HLA-B*58:01-associated mutation, T242N, enhanced viral replication capacity due to pre-existing compensatory polymorphisms in the transmitted/founder virus. A third individual, who had extremely rapid disease progression, was infected with the virus with the highest replication capacity. This thesis describes the complex nature of early immune selection and escape in transmitted/founder viruses. Although attenuating escape mutations were identified in viruses from two individuals, this was not associated with clinical benefit. The extensive variability of epitopes evolving under early selection may implicate many early immune targets as poor candidates for vaccine immunogens; however some early targets may be useful if clinical benefit is conferred through attenuating escape mutations