Sunday, 29 September 2019

Major class of viruses reveals complex origins

A new study examines the evolutionary dynamics of circular Rep-encoding single-stranded (CRESS) DNA viruses. The findings show that this broad class of single-stranded DNA viruses, which infect all three cellular domains of life, have acquired their genetic components through complex evolutionary processes not traceable to a single ancestral event. Rather, viruses are obsessive borrowers, appropriating genetic material from many sources, including bacterial, archaeal and eukaryotic cells as well as circular parasitic replicons, known as plasmids, and other mobile genetic elements, such as transposons.

When a group of mobile elements -- like CRESS DNA viruses -- arise from more than a single common evolutionary ancestor or ancestral group, they are known as polyphyletic. The phenomenon is common in the viral world, presenting both challenges and opportunities for researchers, as the definitions, taxonomies and evolutionary trajectories of this vast domain are reconsidered, with the help of powerful new techniques.

A better understanding of the promiscuous sharing of genetic information between different viruses and cell-derived genetic snippets may one day improve efforts to control these parasitic entities, some of which have had devastating effects on human wellbeing and crop yield.

Such explorations also hold the potential to shed new light on the origins of earth's earliest life, and resolve the question of how cell-based life came to co-exist with the planet's staggering array of viruses (the virome).

Recent research into environmental genomics has shown that the most abundant biological entities on earth are viruses, with virus particles outnumbering cells by one to two orders of magnitude. They display extraordinary diversity and have adapted themselves to virtually all earthly environments. They may also be considered the most successful biological players in terms of their growth potential, abundance, biodiversity, adaptability and impact.

Viruses consist of nucleic acid -- either RNA or DNA -- surrounded by a protective shell, known as the capsid. The job description of every virus is simple: enter a living cell, hijack its metabolic machinery and make progeny.

Viruses differ markedly from cells belonging to the bacterial, eukaryotic and archaeal realms, particularly in terms of their modes of replication. While all cellular life relies on double-stranded DNA inheritance, viruses can be single- or double-stranded and make use of either DNA or RNA as their genetic material. Further, their genomes can be either circular or linear, consisting of single or multiple molecules. Viruses lack a single common ancestor and indeed, not a single gene is conserved across the entire virome, making viruses a sort of genetic collage.

Among the viruses illuminated through viral metagenomics are the CRESS DNA viruses. Once believed to be rare, such viruses have since been uncovered in soils, deep-sea vents, Antarctic lakes and ponds, wastewater samples, oceans and hot springs. CRESS DNA viruses are part of a vast and diverse viral supergroup that is of critical importance, both medically and economically.

CRESS DNA viruses can be identified through a specific protein enzyme, known as Rep. This protein plays a crucial role in the genome replication mechanism common to CRESS DNA viruses as well as diverse circular plasmids found in bacteria and archaea. Researchers have recently noted that the rep gene is conserved in all CRESS DNA viruses. Among their biological tasks is the cutting and rejoining of single-stranded DNA segments -- activity essential to the replication mechanism known as rolling circle replication.

The rolling circle process begins when the Rep protein nicks one of the strands in the dsDNA form of the viral genome, initiating the replication sequence. The loose single strand created by the nick is elongated with the help of a host DNA polymerase, using the un-nicked strand as a template.

Eventually, the newly synthesized single strand of DNA completely dissociates from the original double-stranded form and its ends are joined together into a new single-stranded circle, with the help of Rep. A complementary strand can then form, creating a new double-stranded unit (See Figure 1). The process allows for the rapid synthesis of multiple copies of circular DNA.

Recombination of various functional modules from distinct viral and plasmid groups, derived from across the virosphere is a ceaseless process that is constantly generating new ssDNA viruses. The current study examines sequence similarities between various CRESS DNA viruses and non-viral replicons, such as plasmids, combined with phylogenetic tools used to explore their evolutionary relationships.

The results reveal three distinct evolutionary events contributing to the genetic composition of CRESS-DNA viruses. An intriguing kinship appears to exist between CRESS-DNA viruses and rolling circle plasmids found in bacteria, archaea and some eukaryotes. The new results help to illuminate the expanding galaxy of ssDNA viruses that replicate using the rolling-circle mechanism, among these, the CRESS-DNA viruses.


Darius Kazlauskas, Arvind Varsani, Eugene V. Koonin, Mart Krupovic. Multiple origins of prokaryotic and eukaryotic single-stranded DNA viruses from bacterial and archaeal plasmids. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-11433-0

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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