Two pandemics of respiratory distress diseases associated with zoonotic introductions of the species Severe acute respiratory syndrome-related coronavirus in the human population during 21st... Show moreTwo pandemics of respiratory distress diseases associated with zoonotic introductions of the species Severe acute respiratory syndrome-related coronavirus in the human population during 21st century raised unprecedented interest in coronavirus research and assigned it unseen urgency. The two viruses responsible for the outbreaks, SARS-CoV and SARS-CoV-2, respectively, are in the spotlight, and SARSCoV-2 is the focus of the current fast-paced research. Its foundation was laid down by studies of many coronaand related viruses that collectively form the vast order Nidovirales. Comparative genomics of nidoviruses played a key role in this advancement over more than 30 years. It facilitated the transfer of knowledge from characterized to newly identified viruses, including SARS-CoV and SARS-CoV-2, as well as contributed to the dissection of the nidovirus proteome and identification of patterns of variations between different taxonomic groups, from species to families. This review revisits selected cases of protein conservation and variation that define nidoviruses, illustrates the remarkable plasticity of the proteome during nidovirus adaptation, and asks questions at the interface of the proteome and processes that are vital for nidovirus reproduction and could inform the ongoing research of SARS-CoV-2.(c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
The order Nidovirales, including families Coronaviridae and Arteriviridae, is a monophyletic group of highly divergent (+)ssRNA viruses that infect vertebrate and invertebrate hosts; they share... Show moreThe order Nidovirales, including families Coronaviridae and Arteriviridae, is a monophyletic group of highly divergent (+)ssRNA viruses that infect vertebrate and invertebrate hosts; they share conserved genome organization and replication mechanisms. The genome sequence is the only information available about many newly discovered nidoviruses whose number is fast increasing driven by technology advancements. This development makes comparative genomics, an approach that already has been used extensively in nidovirology, increasingly important. In this thesis, diverse methods of comparative genomics were used to address scientific questions about composition and evolution of the nidovirus genome and proteome, and their connection to the biology of nidoviruses. Three studies were conducted in collaboration with experimental researchers, and ranged from the analysis of the highly divergent polyprotein N-terminus in arteriviruses, to identification of the fifth universally conserved domain of nidoviruses, and to characterization of a nidovirus with the largest known RNA genome. The latter study prompted the development of a bioinformatics tool facilitating functional annotation of large multidomain polyproteins. The thesis illustrates how a notion of nidovirus-specific conservation has been steadily refined as a result of recent discoveries. Show less
This thesis spans several years of work dedicated to understanding fish genomes. In the first chapter it describes the genome of the first fish for which the entire genome was sequenced through a... Show moreThis thesis spans several years of work dedicated to understanding fish genomes. In the first chapter it describes the genome of the first fish for which the entire genome was sequenced through a large-scale international project, Fugu rubripes. the pufferfish. In particular, it highlights how this fish has a genome that contains as many genes as the human genome, although it is ten times smaller. It also shows that the majority of genes that are found in the human genome can be found in this fish genome as well. In the second chapter we compared fish genomes to the human genome to find regions that have been preserved during evolution and which are therefore likely to have a function, even though they are not genes. We showed that indeed they are functional, and they help to regulate other genes. Knowing all the genes in the genome we could then interrogate how they are expressed, i.e. if they are switched __on__ or __off__ and in particular in chapter 4 we looked at how a specific gene is in charge of gradually switching off genes that are inherited from the mother in a newborn fish embryo. Finally in the last chapter since genome sequencing is now becoming much cheaper and simpler to achieve we set out to map the genome of the common carp and we discuss the best approaches and strategies to obtain a good genome sequence for this species. The common carp is a candidate model system for high-troughput screening. Show less
The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs... Show moreThe aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P. falciparum and partial genome sequences of three RMPs (Plasmodium yoelii - Chapter 3; Plasmodium berghei and Plasmodium chabaudi - Chapter 4) enabled us to expand the analysis to a genome-wide survey. By aligning the RMP contigs against the P. falciparum genome, a composite RMP genome was constructed, which was subsequently compared in detail with the P. falciparum genome (Chapter 5). These comparative analyses showed high levels of conservation in both genome organization and gene content (~85%), supporting the use of RMPs as models for human malaria infection. P. falciparum-specific genes located in both subtelomeric and core regions of the chromosomes were also found and included many genes involved in host-parasite interactions, such as host cell invasion and evasion of the human immune response. Finally, reverse genetics approaches were used to study the function of certain genes that are conserved between the rodent and human malaria parasites (Chapters 6 & 7). Show less
