Comparative Analysis Of Completely Sequenced Genomes

National Library Of Medicine

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Abstract

The rapidly growing database of completely and nearly completely sequenced genomes of bacteria, archaea, eukaryotes and viruses (millions of genomes already available and many more in progress) creates both extensive new opportunities and major new challenges for genome research. During the year in review, we performed a variety of studies that took advantage of the genomic information to establish fundamental principles of genome evolution and to investigate the evolution of biologically and medically important groups of organisms. In collaboration with the laboratory of Dr. Mart Krupovic (Institut Pasteur, Paris), we performed a phylogenomic study of viruses infecting Asgardarchaeota. The archaea in this phylum harbor many eukaryotic signature proteins and are widely considered to represent the closest archaeal relatives of eukaryotes. Whether similarities between Asgard archaea and eukaryotes extend to their viromes remains unknown. We analyzed 20 metagenome-assembled genomes of Asgardarchaeota from deep-sea sediments of the basin off the Shimokita Peninsula, Japan. By combining a CRISPR spacer search of metagenomic sequences with phylogenomic analysis, we identified three family-level groups of viruses associated with Asgard archaea. The first group, verdandiviruses, includes tailed viruses of the class Caudoviricetes (realm Duplodnaviria); the second, skuldviruses, consists of viruses with predicted icosahedral capsids of the realm Varidnaviria; and the third group, wyrdviruses, is related to spindle-shaped viruses previously identified in other archaea. More than 90% of the proteins encoded by these viruses of Asgard archaea show no sequence similarity to proteins encoded by other known viruses. Nevertheless, all three proposed families consist of viruses typical of prokaryotes, providing no indication of specific evolutionary relationships between viruses infecting Asgard archaea and eukaryotes. Verdandiviruses and skuldviruses are likely to be lytic, whereas wyrdviruses potentially establish chronic infection and are released without host cell lysis. All three groups of viruses are predicted to play important roles in controlling Asgard archaea populations in deep-sea ecosystems. In connection with the ongoing COVID-19 pandemic, we explored the evolution of human pathogenic viruses during the course of major epidemics. Many pathogenic viruses are endemic among human populations and can cause a broad variety of diseases, some potentially leading to devastating pandemics. How virus populations maintain diversity and what selective pressures drive population turnover is not thoroughly understood. We conducted a large-scale phylodynamic analysis of 27 human pathogenic RNA viruses spanning diverse life history traits, in search of unifying trends that shape virus evolution. For most virus species, we identified multiple, cocirculating lineages with low turnover rates. These lineages appear to be largely noncompeting and likely occupy semiindependent epidemiological niches that are not regionally or seasonally defined. Typically, intralineage mutational signatures are similar to interlineage signatures. The principal exception are members of the family Picornaviridae, for which mutations in capsid protein genes are primarily lineage defining. Interlineage turnover is slower than expected under a neutral model, whereas intralineage turnover is faster than the neutral expectation, further supporting the existence of independent niches. The persistence of virus lineages appears to stem from limited outbreaks within small communities, so that only a small fraction of the global susceptible population is infected at any time. As disparate communities become increasingly connected through globalization, interaction and competition between lineages might increase as well, which could result in changing selective pressures and increased diversification and/or pathogenicity. Thus, in addition to zoonotic events, ongoing surveillance of familiar, endemic viruses appears to merit global attention with respect to the prevention or mitigation of future pandemics. We developed a general theory of genome evolution as a process of multilevel learning. To this end, we formulated seven fundamental principles of evolution that appear to be necessary and sufficient to render a universe observable and show that they entail the major features of biological evolution, including replication and natural selection. It was shown that these cornerstone phenomena of biology emerge from the fundamental features of learning dynamics such as the existence of a loss function, which is minimized during learning. We then sketched the theory of evolution using the mathematical framework of neural networks, which provides for detailed analysis of evolutionary phenomena. To demonstrate the potential of the proposed theoretical framework, we derived a generalized version of the Central Dogma of molecular biology by analyzing the flow of information during learning (back propagation) and predicting (forward propagation) the environment by evolving organisms. We further outlined a phenomenological theory of evolution and origin of life by combining the formalism of classical thermodynamics with a statistical description of learning. The maximum entropy principle constrained by the requirement for minimization of the loss function is employed to derive a canonical ensemble of organisms (population), the corresponding partition function (macroscopic counterpart of fitness), and free energy (macroscopic counterpart of additive fitness). We further define the biological counterparts of temperature (evolutionary temperature) as the measure of stochasticity of the evolutionary process and of chemical potential (evolutionary potential) as the amount of evolutionary work required to add a new trainable variable (such as an additional gene) to the evolving system. We then developed a phenomenological approach to the description of evolution, which involves modeling the grand potential as a function of the evolutionary temperature and evolutionary potential. We demonstrate how this phenomenological approach can be used to study the "ideal mutation" model of evolution and its generalizations. Finally, we show that, within this thermodynamics framework, major transitions in evolution, such as the transition from an ensemble of molecules to an ensemble of organisms, that is, the origin of life, can be modeled as a special case of bona fide physical phase transitions that are associated with the emergence of a new type of grand canonical ensemble and the corresponding new level of description.