Molecular genetics

The research efforts refer to tracking homologus loci in the chromosomes of a pair of a species. The purpose is to infer the extent of maximum syntenic correlation when an exhaustive set of orthologs of the species are searched. Relevant bioinformatic analyses use comparative mapping of conserved synteny via Oxford grid. In medical diagnostic efforts, deducing such synteny correlation can help screening chromosomal aberration in genetic disorder pathology. Objectively, the present study addresses: (i) Cytogenetic framework of syntenic correlation and, (ii) applying information-theoretics to determine entropy-dictated synteny across an exhaustive set of orthologs of the test pairs of species.

Follistatin (FS) proteins are highly conserved inhibitors of Activins, members of the Transforming Growth Factor beta (TGF-beta) family, which play prominent roles in patterning and cell proliferation, and can contribute to tumor formation. Comparison of FS from Drosophila (dFS) and humans (hFS) in flies shows that hFS is less active. The goal of this thesis is to test three possible mechanisms: dFS might be more stable and turn over at a lower rate, exhibit a stronger affinity for ligands, or diffuse less because of stronger interaction with the extracellular matrix. We generated chimeric proteins of dFS and hFS by exchanging individual protein domains. Our results suggest that the increased activity is likely due to ligand binding. Based on the recent structure of the hFS-Activin complex, we speculate that stronger interactions with heparin sulfate in the extracellular matrix may also contribute to the increased activity of dFS.

The Major Histocompatibility Complex (MHC) encodes proteins critical to the vertebrate immune response; therefore MHC diversity is an indicator of population health. I have (1) Isolated exon 2 of the class II gene DQA in Tursiops truncatus in the North Indian River Lagoon (IRL) (n=17), South IRL (n=29) and adjacent Atlantic waters (n=20), (2) assessed genetic variability between groups, (3) developed a method to genotype individuals, (4) typed 11 unique alleles in 66 individuals, (5) detected geographic patterns of diversity between estuarine and coastal individuals (FST=0.1255, p<0.05), (6) found evidence of positive selection centered in the binding pockets P1, P6 and P9 of the peptide binding region (w=2.08), (7) found that patterns of polymorphism did not closely match patterns of diversity in neutral markers, (8) performed a pilot study with Orcinus orca. The initial findings highlight the need for further comparative work and suggest that silent mutations are not neutral.

The bald eagle, Haliaeetus leucocephalus, population declined dramatically in the early 20th century reducing the population from tens of thousands of birds within the lower 48 states, to <450 pairs of birds, effectively inducing a population bottleneck. The overall population has recovered and was removed from the endangered species list in 2007. This study investigates whether such overall population statistics are appropriate descriptors for this widespread species. I investigated the genetic differentiation between three populations of bald eagles from Alaska, North Florida and Florida Bay using both mitochondrial and nuclear DNA loci to determine whether discrete subpopulations comprise the broad range. Significant FST values, for both mtDNA and microsatellites, were found between both Florida populations and Alaska, but not within Florida populations. Results indicate that there is strong population structure, rejecting the null hypothesis of a panmictic population. Future conservation efforts should focus on subpopulations rather than the overall population.