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Study of endogenous retroviruses: Insight into the retroviral evolution and virus-host interactions
Hron, Tomáš ; Elleder, Daniel (advisor) ; Kejnovský, Eduard (referee) ; Hirsch, Ivan (referee)
In my doctoral project, I studied the evolution of retroviruses and long-term interactions with their hosts. Retroviruses infect a broad range of species including possibly all vertebrates. They are unique in their ability to efficiently create endogenous retroviruses (ERVs) - viral copies integrated into the host genomes and consequently inherited by successive generations as usual genomic locus. ERVs represent a significant portion of vertebrate genomes and play an important role in a variety of cellular processes and pathologies; however, their sequences are still largely unexplored. The results of my work contributed to the uncovering of ancient evolutionary history of retroviruses. In this regard, I employed the ERV sequences, as they represent "genetic fossils" of viral infections that occurred throughout entire retroviral evolution. By discovery and analysis of ancient ERV lineages, I shed light on the deep history of retroviruses and revealed how the past infections shaped the evolution of vertebrate antiviral defense. In addition to the investigation of retroviral evolution, I also studied process of ongoing endogenization and fixation of newly emerged ERVs in a mammalian host population. In this part of my work, I focused on a unique model of ERV that have been recently invading mule deer genome.
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Integration site distribution of expressed proviruses
Miklík, Dalibor ; Hejnar, Jiří (advisor) ; Kejnovský, Eduard (referee) ; Indik, Stanislav (referee)
To establish efficient expression of their genes, retroviruses integrate proviral copies into the genomes of the cells they have infected. Epigenetic events, however, silence expression of the integrated proviruses. This silencing protects host cells from harmful viral spread, but also creates a reservoir of latent proviruses that subsequently hinders the cure of retroviral (e.g., HIV-1) infections. Furthermore, the silencing of retrovirus-derived integrative vectors complicates their application in transgenesis and gene therapy. The goal of this thesis is to describe the interaction between retroviral expression and host (epi)genomic environment at the site of proviral integration. To pursue the goal, we sought to define the (epi)genomic environment of the proviruses, which expression is not affected by the epigenetic silencing. Diverse retroviral vectors derived from avian sarcoma and leukosis virus (ASLV), murine leukemia virus (MLV), and human immunodeficiency virus type 1 (HIV-1) were used as model retroviral systems, and expression stability of the vectors in human cell lines was examined. In order to identify the features unique to integration sites of the active proviruses, we sorted the cells positive for the proviral expression, identified their proviral integration sites, and compared them to...
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Study of endogenous retroviruses: Insight into the retroviral evolution and virus-host interactions
Hron, Tomáš ; Elleder, Daniel (advisor) ; Kejnovský, Eduard (referee) ; Hirsch, Ivan (referee)
In my doctoral project, I studied the evolution of retroviruses and long-term interactions with their hosts. Retroviruses infect a broad range of species including possibly all vertebrates. They are unique in their ability to efficiently create endogenous retroviruses (ERVs) - viral copies integrated into the host genomes and consequently inherited by successive generations as usual genomic locus. ERVs represent a significant portion of vertebrate genomes and play an important role in a variety of cellular processes and pathologies; however, their sequences are still largely unexplored. The results of my work contributed to the uncovering of ancient evolutionary history of retroviruses. In this regard, I employed the ERV sequences, as they represent "genetic fossils" of viral infections that occurred throughout entire retroviral evolution. By discovery and analysis of ancient ERV lineages, I shed light on the deep history of retroviruses and revealed how the past infections shaped the evolution of vertebrate antiviral defense. In addition to the investigation of retroviral evolution, I also studied process of ongoing endogenization and fixation of newly emerged ERVs in a mammalian host population. In this part of my work, I focused on a unique model of ERV that have been recently invading mule deer genome.
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Evolution of sex chromosomes and karyotypes in iguanas (Squamata: Pleurodonta)
Altmanová, Marie ; Kratochvíl, Lukáš (advisor) ; Kejnovský, Eduard (referee) ; Zrzavá, Magda (referee)
Evolution of sex chromosomes and karyotypes in iguanas (Squamata: Pleurodonta) PhD Thesis Marie Altmanová Abstract This PhD thesis is composed of five published articles and one manuscript, and is focused on the evolution of the sex chromosomes and karyotype of the iguanas (Pleurodonta). Based on our primary research of available data, only male heterogamety (XX/XY) with ancestral karyotype 2n = 36 chromosomes was recorded in iguanas. However, in many species sex chromosomes have not been uncovered by classical cytogenetics, probably due to their homomorphy. The partially-known X chromosome content of Anolis carolinensis allowed us to compare the relative gene doses of X-specific genes between male and female of representatives of all iguana families, and to reveal homologous and well-differentiated sex chromosomes across all iguanas, with the exception of basilisks. Thus, due to the comparable age with sex chromosomes of mammals and birds, the results put into question the importance of endothermy for the formation of stable sex chromosomes. The striking feature of the iguanas is the relatively frequent occurrence of multiple sex chromosomes in their karyotypes. Using the ancestral state analysis of the type of sex chromosomes, it has been found that these multiple sex chromosomes developed at least twelve...
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Linguistic -like approaches in geomics and linguistic metaphor in biology
Nohejlová Zemková, Michaela ; Flegr, Jaroslav (advisor) ; Faltýnek, Dan (referee) ; Kejnovský, Eduard (referee)
In this work we present articles which are connected by the topic of linguistic-like approaches in genomics, which allow to treat genetic sequences as a "text" containing potential "words" (oligonukleotides, oligopeptides) of length n. Such an approach stands on the border of quantitative and qualitative analysis and, contrary to standard comparative bioinformatics methods, it is possible to compare phylogenetically distant individuals. Central article of my work (Zemková et al., 201..) is an analysis of peptide vocabularies of parasites and free-living organisms which showed significant differences in diversity of 4-6 amino acids long peptides of these compared groups. Parasites generally display reduction of pentapeptides, which is partly compensated by increased diversity of hexapeptides. This result is in accordance with our a priori hypothesis that parasites use immune evasion strategy to escape from MHC-based immunity system of its vertebrate host. Results also suggest that the length of key region for peptide recognition is about 4-5 amino acids and hence only short part of longer peptide bound in MHC participate on reaction with T-receptor. In other two articles which arose as a product of cooperation with Prof Trifonov from the University of Haifa, we again used an analysis of genomic...
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Structure and evolution of plant sex chromosomes: The use of BAC library
Kejnovský, Eduard ; Lengerová, Martina ; Hobza, Roman ; Široký, Jiří ; Vyskot, Boris
Sex chromosomes of plant species Silene latifolia are the ideal model for evolutionary biology studies because they represent early stages of X and Y chromosomes history. We used fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones in studies of chromosome structure to demonstrate that a majority of genes are located in subtelomeric regions of all chromosomes. Our results also indicate the absence of accumulation of main classes of repetitive sequences - retroelements and centromeric tandem repeats - in non-recombining parts of the sex chromosomes.
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