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- Creators: Barrett, The Honors College
Description
Plasmodium falciparum and Plasmodium vivax are two of the main propagators of human malaria. Both species contain the protein, Apical Membrane Antigen 1 (AMA-1), which is involved in the process of host cell invasion. However, the high degree of polymorphisms and antigenic diversity in this protein has prevented consistent single-vaccine success. Furthermore, the three main domains within AMA-1 (Domains I, II, and III), possess variable polymorphic features and levels of diversity. Overcoming this issue may require an understanding of the type of selection acting on AMA-1 in P. falciparum and P. vivax. Therefore, this investigation aimed to determine the type of selection acting on the whole AMA-1 coding sequence and in each domain for P. falciparum and P. vivax. Population structure was investigated on a global scale and among individual countries. AMA-1 sequences were obtained from the National Center for Biotechnology. For P. falciparum, 649 complete and 382 partial sequences were obtained. For P. vivax, 395 sequences were obtained (370 partial). The AMA-1 gene in P. falciparum was found to possess high nonsynonymous polymorphisms and disproportionately low synonymous polymorphisms. Domain I was found to have the most diverse region with consistently high nonsynonymous substitutions across all countries. Large, positive, and significant Z-test scores indicated the presence of positive selection while FST and NST values showed low genetic differentiation across populations. Data trends for all analyses were relatively consistent for the global and country-based analyses. The only country to deviate was Venezuela, which was the only South American country analyzed. Network analyses did not show distinguishable groupings. For P. falciparum, it was concluded that positive diversifying selection was acting on the AMA-1 gene, particularly in Domain I. In AMA-1 of P. vivax, nonsynonymous and synonymous polymorphisms were relatively equal across all analyses. FST and NST values were high, indicating that countries were genetically distinct populations. Network analyses did not show distinguishable grouping; however, the data was limited to small sample sizes. From the data, it was concluded that AMA-1 in P. vivax was evolving neutrally, where selective pressures did not strongly encourage positive or purifying selection specifically. In addition, different AMA-1 P. vivax strains were genetically distinct and this genetic identity correlated with geographic region. Therefore, AMA-1 strains in P. falciparum and P. vivax not only evolve differently and undergo different form of selection, but they also require different vaccine development strategies. A combination of strain-specific vaccines along with preventative measures on an environmental level will likely be more effective than trying to achieve a single, comprehensive vaccine.
ContributorsEspinas, Jaye Frances Palma (Author) / Escalante, Ananias (Thesis director) / Taylor, Jay (Committee member) / Rosenberg, Michael (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Phenotypic evolution is an essential topic within the general field of evolution. Theoretically, the outcome of phenotypic evolution may be influenced by factors such as genetic background and the interaction of natural selection and genetic drift. To gain empirical evidence for testing the effects of those factors, we used eight long-term evolved Escherichia coli populations as a model system. These populations differ in terms of genetic background (different mutation rates) as well as bottleneck size (small- and large-magnitude). Specifically, we used a plate reader to measure three growth-related traits: maximum growth rate (umax), carrying capacity (Kc), and lag time (Lt) for 40 clones within each population. For each trait we quantified the change in mean per generation, the change in variance per generation, and the correlation coefficient between pairs of traits. Interestingly, we found that the small and large bottleneck populations of one background displayed clear, distinguishing trends that were not present within the populations of the other background. This leads to the conclusion that the influence of selection and drift on a population’s phenotypic outcomes is itself influenced by the genetic background of that population. Additionally, we found a strong positive correlation between umax and Kc within each of the high-mutation populations that was not consistent with our neutral expectation. However, the other two pairs did not exhibit a similar pattern. Our results provide a novel understanding in the relationship between the evolution of E. coli growth-related phenotypes and the population-genetic environment.
ContributorsGonzales, Jadon (Co-author, Co-author) / Lynch, Michael (Thesis director) / Ho, Wei-Chin (Committee member) / Geiler-Samerotte, Kerry (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05