Comparative and Evolutionary genomics of Nucleocytoviricota

Autor: Karki, Sangita
Jazyk: angličtina
Rok vydání: 2024
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Druh dokumentu: Dissertation
Popis: Viruses have been historically identified by their smaller sizes and simple genomic features compared to cellular life forms. Advances in virus cultivation and metagenomic analysis in recent years have shown that giant viruses, classified within the phylum Nucleocytoviricota, possess remarkably large genomes and complex structures, rivaling those of bacteria. Apart from their unusual genome and virion size, these nucleocytoviruses also encode Eukaryotic signature proteins (ESPs), including membrane trafficking proteins, cytoskeletal components, histones, ubiquitin signaling, and components of RNA and DNA processing proteins that are hallmarks of their eukaryotic hosts. Despite these intriguing findings, many groups of nucleocytoviruses remain underexplored. Similarly, their genomic complexity for example large genome size and encoded ESPs raise important questions about the role of nucleocytoviruses in the origins and evolution of eukaryotic hosts cells. In my work, I address this gap by performing comparative genomics and phylogenetic analysis to explore the genomics and evolutionary dynamics of giant viruses. In Chapter 1, I provide a literature review on giant viruses, their history, and their evolutionary links with eukaryotes. This chapter establishes the necessary background for the subsequent chapters. In Chapter 2, I perform comparative genomics, phylogenetics, and environmental distribution analysis to provide insights into the genomes and biogeography of the members of Asfarviridae family in the Nucleocytoviricota. In this chapter, I show that these viruses are widespread in the ocean, they have genes involved in different metabolic processes, and the members within this family have broad genomic diversity. In Chapter 3 and 4, I perform comprehensive phylogenetic analysis to uncover the co-evolutionary dynamics of nucleocytoviruses and eukaryotes. In Chapter 3, I focus on the vesicular trafficking and transport, ubiquitin system, and cytoskeleton system proteins to uncover complex patterns of gene exchange. My findings reveal that these proteins were acquired relatively recently by viruses, and in some cases multiple times independently suggesting that these genes might be important for countering the host changing environments and immune defenses. Similarly, in chapter 4, I focus on the replication and transcriptional machinery to study the ancient co-evolutionary dynamics of the virus and its host. My findings show that the DNA polymerase, especially the eukaryotic delta polymerase, a key processive polymerase required for genome replication in all eukaryotes, clusters adjacent to an ancient viral clade. The viral enzymes forming deep-branching clades adjacent to eukaryotic lineages, suggests their origin predates the Last Eukaryotic Common Ancestor (LECA). The replication and transcription machinery needed for viroplasm hints at an ancient virosphere with relics from extinct proto-eukaryotic lineages. Overall, these studies highlight the ancient as well as recent gene acquisition patterns between nucleocytoviruses and the hosts and provide valuable insight into the coevolutionary dynamics of these groups.
Doctor of Philosophy
Viruses are tiny infectious agents, often too small to be seen with a light microscope. However, a unique group of viruses called "Nucleocytoviricota" aka Nucleocytoviruses, stands out due to their unusually large size. In fact, their virion size is comparable to that of bacteria like Escherichia coli. These viruses not only possess larger physical dimensions but also boast much larger genomes compared to typical viruses, earning them the name "Giant Viruses." When nucleocytoviruses were first discovered, they were mistakenly thought to be bacteria because of the longstanding belief that viruses are universally small. Unlike most viruses, which tend to have icosahedral shapes, nucleocytoviruses often exhibit more complex forms. This unusual shape also contributed to their delayed discovery. Much like other viruses, nucleocytoviruses are classified into different families within the Nucleocytoviricota group. Since their first official discovery in 2003, numerous nucleocytoviruses have been identified. However, one family, Asfarviridae, has been less extensively studied, leaving room for further exploration and understanding. In my second chapter, we study the genetic makeup of Asfarviruses to see how they are related and how they differ from each other. We also investigate where these viruses are found in nature, such as in oceans, freshwater, and soil, to better understand their role in different environments. By looking at the genetic makeup of various species, we can learn how organisms are related, how they evolved, and what genes are responsible for specific traits or functions. The family Asfarviridae is best known for the African swine fever virus (ASFV) which is a terrestrial pathogen for swine, yet recent discoveries of other Asfarviridae members suggest a diverse and cosmopolitan group. To explore this family, we analyzed five complete genomes and 35 metagenome-assembled genomes (MAGs) from various environments, including marine, freshwater, and terrestrial habitats. Evolutionary analysis and whole genome comparison revealed high genomic diversity within this family. Their genomic analysis also revealed the presence of genes with various metabolic functions and links to other domains of life highlighting the unique genomic chimerism of these viruses. Notably, some Asfarviruses genomes were found to be widespread in marine environments, potentially infecting ecologically important protists, further underscoring their environmental and evolutionary significance. In this way, my second chapter deals with the environmental distribution and comparative genomics of these nucleocytoviruses, specifically the Asfarviridae. Apart from their unusually large genome and physical size, these nucleocytoviruses possess genes typically found only in eukaryotes. They include genes involved in key processes like DNA replication, RNA production, and protein synthesis, all of which are essential for the host's survival. Additionally, they encode genes related to membrane trafficking, ubiquitin regulation, transport, and the cytoskeleton, which are important for the host's ability to maintain cellular organization, regulate protein degradation, and support structural integrity. What makes these viruses fascinating is that they carry these critical genes themselves. In my third and fourth chapters, I explore the evolutionary processes that led to this unique feature. Findings from my third chapter showed that the genes such as those for membrane trafficking and transport, ubiquitin signaling, and the cytoskeleton in the nucleocytoviruses were acquired from their host more recently likely important for the viruses to adapt to host changing environment and evade host immune defenses. Similarly, findings from my fourth chapter indicate that nucleocytoviruses are ancient, carrying genes involved in crucial processes such as DNA replication and RNA transcription, specifically the DNA Polymerase B and RNA polymerase genes. The clustering of these eukaryotic genes within viral group likely reflects an acquisition of these genes from extinct proto-eukaryotes by the ancient viruses, rather than a transfer to eukaryotes. This suggests that nucleocytoviruses retain relics of ancient gene exchanges, highlighting the complex evolutionary interactions that shaped both giant viruses and early eukaryotic lineages.
Databáze: Networked Digital Library of Theses & Dissertations
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