Cell Biology & Molecular Genetics

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    Functional divergence of gene duplicates – a domain-centric view
    (Springer Nature, 2012-07-27) Khaladkar, Mugdha; Hannenhalli, Sridhar
    Gene duplicates have been shown to evolve at different rates. Here we further investigate the mechanism and functional underpinning of this phenomenon by assessing asymmetric evolution specifically within functional domains of gene duplicates. Based on duplicate genes in five teleost fishes resulting from a whole genome duplication event, we first show that a Fisher Exact test based approach to detect asymmetry is more sensitive than the previously used Likelihood Ratio test. Using our Fisher Exact test, we found that the evolutionary rate asymmetry in the overall protein is largely explained by the asymmetric evolution within specific protein domains. Moreover, among cases of asymmetrically evolving domains, for the gene copy containing a fast evolving domain, the non-synonymous substitutions often cluster within the fast evolving domain. We found that rare substitutions were preferred within asymmetrically evolving domains suggestive of functional divergence. While overall ~32 % of the domains tested were found to be evolving asymmetrically, certain protein domains such as the Tyrosine and Ser/Thr Kinase domains had a much greater prevalence of asymmetric evolution. Finally, based on the spatial expression of Zebra fish duplicate proteins during development, we found that protein pairs containing asymmetrically evolving domains had a greater divergence in gene expression as compared to the duplicate proteins that did not exhibit asymmetric evolution. Taken together, our results suggest that the previously observed asymmetry in the overall duplicate protein evolution is largely due to divergence of specific domains of the protein, and coincides with divergence in spatial expression domains.
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    Evolution of Pair-rule genes
    (2015) Lu, Yong; Pick, Leslie; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    All insects have a segmented body. The genes controlling segment development have been well characterized in the fruit fly, Drosophila melanogaster. These genes were divided into three categories: gap genes specify several continuous segments over a broad region of the embryo; Pair-Rule Genes (PRG) are responsible for segment formation and are the first set of genes to be expressed in repetitive patterns in the embryo; Segment polarity genes define anterior and posterior polarities within each segment.To understand how PRGs evolve, I took a comparative approach in this thesis. First, I compared the function of the Drosophila PRG ftz-f1 to that of its mammalian orthologs by expressing them all in Drosophila embryos. I found that the molecular function of this family of nuclear receptors has been highly conserved during evolution. Next, I set out to establish new insect model systems to study PRG function. While, some PRGs have been studied in other insects, most of these studies focused on holometabolous insects. My work focused on the sister group to the holometabolous insects, the Hemipteroid Assemblage. I participated in the genome annotation of a hemipteras insect, Oncopeltus fasciatus. I annotated nuclear receptor super family, Hox and PRGs in Oncopeltus. I further studied the expression and function of four PRGs in Oncopeltus. Using in situ hybridization and RNAi, I found that, Of-ftz and Of-hairy do not have segmentation function, while Of-ftz-f1 has function in oogenesis and segmentation. Of-runt was found to induce cell death in oocytes, but its function in segmentation needs further analysis. Using the knowledge and expertise I gained from Oncopeltus, I successfully set up in situ hybridization, antibody staining and parental RNAi in an invasive hemipteran insect pest, the Brown Marmorated Stink Bug (BMSB) Halyomorpha halys. These studies show that the expression and function of PRGs varies extensively in diverse insects, despite the overall conservation of a segmented body plan.