Evolution of HIV-1 env sequences was studied in 15 seroconverting injection drug users selected for differences in the extent of CD4 T cell decline. The rates of increase of either sequence diversity at a given visit or divergence from the first seropositive visit were both higher in progressors than in nonprogressors. Viral evolution in individuals with rapid or moderate disease progression showed selection favoring nonsynonymous mutations, while nonprogressors with low viral loads selected against the nonsynonymous mutations that might have resulted in viruses with higher levels of replication. For 10 of the 15 subjects no single variant predominated over time. Evolution away from a dominant variant was followed frequently at a later time point by return to dominance of strains closely related to that variant. The observed evolutionary pattern is consistent with either selection against only the predominant virus or independent evolution occurring in different environments within the host. Differences in the level to which CD4 T cells fall in a given time period reflect not only quantitative differences in accumulation of mutations, but differences in the types of mutations that provide the best adaptation to the host environment.
We examine how genomic imprinting may have evolved at an X-linked locus, using six diallelic models of selection in which one allele is imprintable and the other is not. Selection pressures are generated by genetic conflict between mothers and their offspring. The various models describe cases of maternal and paternal inactivation, in which females may be monogamous or bigamous. When inactivation is maternal, we examine the situations in which only female offspring exhibit imprinting as well as when both sexes do. We compare our results to those previously obtained for an autosomal locus and to four models in which a dominant modifier of biallelic expression is subjected to the same selection pressures. We find that, in accord with verbal predictions, maternal inactivation of growth enhancers and paternal inactivation of growth inhibitors are more likely than imprinting in the respective opposite directions, although these latter outcomes are possible for certain parameter combinations. The expected outcomes are easier to evolve than the same outcomes for autosomal loci, contradicting the available evidence concerning the direction of imprinting on mammalian sex chromosomes. In most of our models stable polymorphism of imprinting status is possible, a behavior not predicted by verbal accounts.
With advances in computing, agent-based models (ABMs) have become a feasible and appealing tool to study biological systems. ABMs are seeing increased incorporation into both the biology and mathematics classrooms as powerful modeling tools to study processes involving substantial amounts of stochasticity, nonlinear interactions, and/or heterogeneous spatial structures. Here we present a brief synopsis of the agent-based modeling approach with an emphasis on its use to simulate biological systems, and provide a discussion of its role and limitations in both the biology and mathematics classrooms.
Bioinformatics is central to biology education in the 21st century. With the generation of terabytes of data per day, the application of computer-based tools to stored and distributed data is fundamentally changing research and its application to problems in medicine, agriculture, conservation and forensics. In light of this 'information revolution,' undergraduate biology curricula must be redesigned to prepare the next generation of informed citizens as well as those who will pursue careers in the life sciences. The BEDROCK initiative (Bioinformatics Education Dissemination: Reaching Out, Connecting and Knitting together) has fostered an international community of bioinformatics educators. The initiative's goals are to: (i) Identify and support faculty who can take leadership roles in bioinformatics education; (ii) Highlight and distribute innovative approaches to incorporating evolutionary bioinformatics data and techniques throughout undergraduate education; (iii) Establish mechanisms for the broad dissemination of bioinformatics resource materials and teaching models; (iv) Emphasize phylogenetic thinking and problem solving; and (v) Develop and publish new software tools to help students develop and test evolutionary hypotheses. Since 2002, BEDROCK has offered more than 50 faculty workshops around the world, published many resources and supported an environment for developing and sharing bioinformatics education approaches. The BEDROCK initiative builds on the established pedagogical philosophy and academic community of the BioQUEST Curriculum Consortium to assemble the diverse intellectual and human resources required to sustain an international reform effort in undergraduate bioinformatics education.
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