Why study evolution? Best conceptual framework for understanding
Why study evolution? Best conceptual framework for understanding origins of biodiversity Adaptations that allow organisms to exploit their environment
Self discovery Keystone of biology (including human health) cture: HIV Motivation
at can we learn when we apply evolutionary principles to our understanding of the he HIV epidemic?? Can we use HIV to introduce us to evolutionary principles Natural Selection
Mutation Gene Flow Descent with Modification II. Prevalence & Effect
HIV is a natural selective agent Life expectancy in Botswana
III. Basic Biology of HIV and Human Immunoresponse Infectious stage *
Reverse transcriptase Helper T-cell 11. HIV replication = T-cell death
IV. HIV Treatment How AZT blocks reverse transcriptase pyrimidine
V. Evolution of HIV in Host AZT is a selective agent On HIV
Needed to prevent replication in t-tubes Can we predict the changes in Reverse Transcriptase* using
evolutionary principles?? *due to AZT HIV Contributes to Collapse of Immune System in 3 Ways:
. Continuous evolution of HIV proteins used by human immune system to recognize HIV . Evolution towards more and more aggressive replication
. HIV often evolve to infect different immune cells (nave T cells) using different immune cell receptor proteins Evolution at gp120 locus
Years since patient became HIV Positive Neutral evolution and progression to AIDS Evolutionary tree for one patient
Across patients progress to AIDS HIV strains evolve to become more competitive HIV evolves to recognize the CXCR4 receptor on Nave helper T cells
VI. Evolution of the Host, Evidence for Genetic Variation for Resistance HIV-1 interacts with a cell-surface receptor, primarily CD4, and through conformational changes becomes more closely associated with the cell
through interactions with other cell-surface molecules, such as the chemokine receptors CXCR4 and CCR5. Two loci in human populations confer resistance to HIV
Deletion in CCR5 locus Genetic variation In Africa for Resistance to HIV
Sex workers in Kenya having a C instead of a T at position 868 for CD4 have resistance to
HIV VII. Evolution of Human Specific HIV Multiple evolution of HIV
Group M HIV-1 Strains Innocent
Guilty Evidence VIII. HIV is a good model to start us thinking in evolutionary terms:
1. Selective agents on host and disease 2. Source or origin of disease 3. Strategies to combat HIV Highlights evolutionary theory: Natural selection
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