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Experimental Evolution of RNA Viruse...

Morley, Valerie J.

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Experimental Evolution of RNA Viruses in Multi-host Environments.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Experimental Evolution of RNA Viruses in Multi-host Environments./
作者:	Morley, Valerie J.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2017,
面頁冊數:	203 p.
附註:	Source: Dissertation Abstracts International, Volume: 78-11(E), Section: B.
Contained By:	Dissertation Abstracts International78-11B(E).
標題:	Evolution & development. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10632522
ISBN:	9780355027716

Experimental Evolution of RNA Viruses in Multi-host Environments.
Morley, Valerie J.

Experimental Evolution of RNA Viruses in Multi-host Environments. - Ann Arbor : ProQuest Dissertations & Theses, 2017 - 203 p.

Source: Dissertation Abstracts International, Volume: 78-11(E), Section: B.

Thesis (Ph.D.)--Yale University, 2017.

In nature RNA viruses navigate complex environments where they may encounter multiple types of hosts. This heterogeneity among host types occurs at multiple levels: viruses may encounter different cell types within a tissue, different tissue types within a host, and different host genotypes or species within a community. Successful replication on different host types is especially important for arthropod-borne viruses (arboviruses), which obligately cycle between vertebrate and arthropod hosts. In the work presented here, we used experimental evolution to investigate how arbovirus populations evolve in response to complex multi-host communities. The motivation of these experiments was two-fold. First, understanding the evolution of host range in RNA viruses is important to understanding disease emergence. Therefore, understanding how viruses evolve in response to the composition of their host communities has implications for public health. Second, RNA viruses serve as a fast-evolving model system that can give basic insight into how asexual populations respond to environmental complexity. In this sense, these experiments contribute to our general knowledge of how heterogeneous environments shape adaptive dynamics.

ISBN: 9780355027716Subjects--Topical Terms:

3172418
Evolution & development.

Experimental Evolution of RNA Viruses in Multi-host Environments.
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300 $a 203 p.
500 $a Source: Dissertation Abstracts International, Volume: 78-11(E), Section: B.
500 $a Adviser: Paul E. Turner.
502 $a Thesis (Ph.D.)--Yale University, 2017.
520 $a In nature RNA viruses navigate complex environments where they may encounter multiple types of hosts. This heterogeneity among host types occurs at multiple levels: viruses may encounter different cell types within a tissue, different tissue types within a host, and different host genotypes or species within a community. Successful replication on different host types is especially important for arthropod-borne viruses (arboviruses), which obligately cycle between vertebrate and arthropod hosts. In the work presented here, we used experimental evolution to investigate how arbovirus populations evolve in response to complex multi-host communities. The motivation of these experiments was two-fold. First, understanding the evolution of host range in RNA viruses is important to understanding disease emergence. Therefore, understanding how viruses evolve in response to the composition of their host communities has implications for public health. Second, RNA viruses serve as a fast-evolving model system that can give basic insight into how asexual populations respond to environmental complexity. In this sense, these experiments contribute to our general knowledge of how heterogeneous environments shape adaptive dynamics.
520 $a Chapter I reviews the history of experimental evolution with viruses. Experiments in virus evolution have led to insights into the dynamics of adaptation, the distribution of mutational fitness effects, the process of clonal interference, selective sweeps, the prevalence and nature of epistatic interactions, and genetic drift. This chapter highlights the advantages of viruses as a model system, and points to unresolved questions in the field of experimental virus evolution.
520 $a Chapter 2 describes an experiment comparing the evolution of virus populations in environments containing a single host cell type versus environments containing mixtures of two host cell types. Vesicular stomatitis virus (VSV) lineages were allowed to evolve in replicated environments containing BHK-21 cells, HeLa cells, or mixtures of the two host cells. Results showed that generalist phenotypes dominated in evolved virus populations across all treatments. We observed greater variance in host-use performance among VSV lineages evolved in mixed host environments, relative to lineages evolved in single-host environments. Deep sequencing of evolved populations revealed that this divergence was correlated with a larger number of minority genetic variants in evolved populations.
520 $a The experiment presented in Chapter 3 explores virus evolution in environments where a new host cell type invaded the environment suddenly versus gradually. We experimentally evolved 144 Sindbis virus (SINV) lineages in replicated tissue-culture environments, which transitioned from being dominated by a permissive host cell type to a novel host cell type. We found that viruses evolved higher fitness on the novel host in response to more gradual environmental turnover. More gradual turnover also led to higher genetic convergence between evolved replicate populations. Analysis of wholegenome consensus sequences suggested that epistatic interactions and historical contingency play important roles in the molecular evolution of these populations. Chapter 4 describes how the rate of environmental turnover affected the dynamics of molecular adaptation in SINV populations. We used whole-genome next-generation sequencing to track changes in allele frequencies over time in the SINV populations described in Chapter 3. In support of theoretical models, we found that when populations evolved in response to a sudden environmental change, mutations of large beneficial effect tended to fix early, followed by mutations of smaller beneficial effect; as predicted, this pattern broke down in response to a gradual environmental change. Patterns of molecular evolution were dominated by the spread of cohorts of associated mutations rather than by mutations fixing singly, and this bias towards mutational cohorts was more extreme when the environment changed gradually. Additionally, clonal interference appeared stronger on average in response to a gradual change.
520 $a In Chapter 5 we report how virus populations evolved in response to a large genomic deletion in the 3'untranslated region (UTR), which plays a role in determining alphavirus host range. Deletion and insertion are thought to be key mutational mechanisms driving 3'UTR evolution. We engineered a chikungunya virus (CHIKV) mutant with a large deletion in the 3"UTR. This deletion inhibited viral replication on mosquito cells, but not mammalian cells. We then passaged replicated virus populations strictly on primate cells, strictly on mosquito cells, or with alternating primate/mosquito passages. We found that virus populations passaged on a single host increased in fitness relative to the ancestral deletion mutant on their selected host, and viruses that were alternately passaged improved on both hosts. Surprisingly, whole genome sequencing revealed few changes in the 3'UTR of evolved populations. However, we identified highly convergent mutations across replicate virus populations that associated with specific hosts.
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