Wednesday, April 2, 2014

On the Origin of the Genes of Viruses - 2

RNA & DNA: post-carbon
Using our "mind's eye", our imagination, can we place ourselves inside the world which was on Earth in an epoch that evolutionary scientists say existed prior to the time when carbon-based life forms first appeared?

A world on Earth where the beginnings of viruses are said to be found in a gene pool before carbon-based life forms existed?

A place where only forces, quanta, molecules, and atoms existed, but nevertheless a place that some evolutionary hypotheses say we can explore, because a lot of scientists have been pondering that world for a long time:
Recent advances in genomics of viruses and cellular life forms have greatly stimulated interest in the origins and evolution of viruses and, for the first time, offer an opportunity for a data-driven exploration of the deepest roots of viruses. Here we briefly review the current views of virus evolution and propose a new, coherent scenario that appears to be best compatible with comparative-genomic data and is naturally linked to models of cellular evolution that, from independent considerations, seem to be the most parsimonious among the existing ones.
The existence of several genes that are central to virus replication and structure, are shared by a broad variety of viruses but are missing from cellular genomes (virus hallmark genes) suggests the model of an ancient virus world, a flow of virus-specific genes ... existence of a complex, precellular, compartmentalized but extensively mixing and recombining pool of genes ...
(The ancient Virus World and evolution of cells, emphasis added). That would be the genes of viruses (e.g. virions, viroids, or other first-time prototypes of viruses) that existed prior to carbon-based single cell life forms.

So, where did these genes come from, these non-living genes, these molecular entities that are still non-living genes, these genes that are still non-living molecular entities in us all in today's world on Earth?

When we look at modern viruses they lack what their host cells do not lack, which is the ribosome ("The ribosome ... is a large and complex molecular machine." - Wikipedia, "Ribosome") which now does various types of genetic manipulation of the RNA and/or DNA instead of the viruses themselves doing it with their own internal complex molecular machinery.

The RNA of early viruses before carbon-based life evolved was processed in a different manner than it is now.
Ribosome: a sophisticated molecular machine

The modern virus needs a host with ribosome molecular machinery in order to reproduce.

But, where was the ribosome in the pre-cellular world of viruses we are thinking about today?

The ribosomes of the major cell types differ from one another: "Ribosomes from bacteria, archaea and eukaryotes (the three domains of life on Earth) differ in their size, sequence, structure, and the ratio of protein to RNA" (ibid, Wikipedia, "Ribosomes").

Previously we noted that in addition to the ribosome's molecular machinery, smaller molecular machines associated with genetic dynamics have been discovered:
"We took this approach because so many RNAs are rapidly destroyed soon after they are made, and this makes them hard to detect," Pugh said. "So rather than look for the RNA product of transcription we looked for the 'initiation machine' that makes the RNA. This machine assembles RNA polymerase, which goes on to make RNA, which goes on to make a protein." Pugh added that he and Venters were stunned to find 160,000 of these "initiation machines," because humans only have about 30,000 genes. "This finding is even more remarkable, given that fewer than 10,000 of these machines actually were found right at the site of genes. Since most genes are turned off in cells, it is understandable why they are typically devoid of the initiation machinery."

The remaining 150,000 initiation machines -- those Pugh and Venters did not find right at genes -- remained somewhat mysterious. "These initiation machines that were not associated with genes were clearly active since they were making RNA and aligned with fragments of RNA discovered by other scientists," Pugh said. "In the early days, these fragments of RNA were generally dismissed as irrelevant ["junk"] since they did not code for proteins." Pugh added that it was easy to dismiss these fragments because they lacked a feature called polyadenylation -- a long string of genetic material, adenosine bases -- that protect the RNA from being destroyed. Pugh and Venters further validated their surprising findings by determining that these non-coding initiation machines recognized the same DNA sequences as the ones at coding genes, indicating that they have a specific origin and that their production is regulated, just like it is at coding genes.
(Scientists Discover the Origins, emphasis added). So, the ribosome is not the only molecular machine in the game.

The direction this is going is that ancient viruses replicated themselves with pre-ribosome molecular machinery, "pre-ribosomes" which later ended up in cells.

Once there, this hypothesis goes, the pre-ribosome naturally evolved differently within the different types of cells, into what we currently know as the ribosome.

This is reminiscent of a once-rejected scientific theory which is now no longer rejected by scientific consensus:
Thus "symbionticism" and "symbiogenesis" theory could no longer be ignored, because the evidence was mounting:
Entire genomes with their accompanying protein synthetic systems are transferred throughout the biosphere primarily as bacteria and protists which become symbionts as they irreversibly integrate into pre-existing organisms to form more complex individuals. Individualization is stabilized by simultaneous transmission of once-separate heterologous genetic systems. The origin of new species is hypothesized to correlate with the acquisition, integration and subsequent inheritance of such acquired microbial genomes. These processes were recognized by Mereschkovsky (“Symbiogenesis” in Russian, 1909) and by Wallin (“Symbionticism”, see p. 181, this issue).
(Origins of Species). That paper, written by Dr. Lynn Margulis, Department of Biology, University of Massachusetts, concerns "acquired genomes and individuality."
(Are Microbes The Origin of PTSD?). Another interesting paper concerning the ribosome gives some additional perspective:
The modern ribosome was largely formed at the time of the last common ancestor, LUCA. Hence its earliest origins likely lie in the RNA world. Central to its development were RNAs that spawned the modern tRNAs and a symmetrical region deep within the large ribosomal RNA, (rRNA), where the peptidyl transferase reaction occurs. To understand pre-LUCA developments, it is argued that events that are coupled in time are especially useful if one can infer a likely order in which they occurred. Using such timing events, the relative age of various proteins and individual regions within the large rRNA are inferred. An examination of the properties of modern ribosomes strongly suggests that the initial peptides made by the primitive ribosomes were likely enriched for l-amino acids, but did not completely exclude d-amino acids. This has implications for the nature of peptides made by the first ribosomes. From the perspective of ribosome origins, the immediate question regarding coding is when did it arise rather than how did the assignments evolve. The modern ribosome is very dynamic with tRNAs moving in and out and the mRNA moving relative to the ribosome. These movements may have become possible as a result of the addition of a template to hold the tRNAs. That template would subsequently become the mRNA, thereby allowing the evolution of the code and making an RNA genome useful. Finally, a highly speculative timeline of major events in ribosome history is presented and possible future directions discussed.
(Origin and Evolution of the Ribosome, emphasis added). There are some other indicators for an ancient virus world.

Those data indicate that ancient viruses reproduced prior to the existence of the current modern ribosome:
The discovery of a giant virus that falls ill through infection by another virus is fuelling the debate about whether viruses are alive.

“There’s no doubt this is a living organism,” says Jean-Michel Claverie, a virologist at the the CNRS UPR laboratories in Marseilles, part of France’s basic-research agency. “The fact that it can get sick makes it more alive.”

Giant viruses have been captivating virologists since 2003, when a team led by Claverie and Didier Raoult at CNRS UMR, also in Marseilles, reported the discovery of the first monster2. The virus had been isolated more than a decade earlier in amoebae from a cooling tower in Bradford, UK, but was initially mistaken for a bacterium because of its size, and was relegated to the freezer.
Viruses: Dead & Alive?

Closer inspection showed the microbe to be a huge virus with, as later work revealed, a genome harbouring more than 900 protein-coding genes3 — at least three times more than that of the biggest previously known viruses and bigger than that of some bacteria. It was named Acanthamoeba polyphaga mimivirus (for mimicking microbe), and is thought to be part of a much larger family. “It was the cause of great excitement in virology,” says Eugene Koonin at the National Center for Biotechnology Information in Bethesda, Maryland. “It crossed the imaginary boundary between viruses and cellular organisms.”
Now Raoult, Koonin and their colleagues report the isolation of a new strain of giant virus from a cooling tower in Paris, which they have named mamavirus because it seemed slightly larger than mimivirus. Their electron microscopy studies also revealed a second, small virus closely associated with mamavirus that has earned the name Sputnik, after the first man-made satellite.

With just 21 genes, Sputnik is tiny compared with its mama — but insidious. When the giant mamavirus infects an amoeba, it uses its large array of genes to build a ‘viral factory’, a hub where new viral particles are made. Sputnik infects this viral factory and seems to hijack its machinery in order to replicate. The team found that cells co-infected with Sputnik produce fewer and often deformed mamavirus particles, making the virus less infective. This suggests that Sputnik is effectively a viral parasite that sickens its host — seemingly the first such example.
('Virophage' suggests viruses are alive, emphasis added). Well, what it suggests to me is: 1) that some viruses today may be "alive," others not alive, 2) that some viruses can infect other viruses (replicate within another virus), 3) that some may still replicate via another virus' internal mechanisms, and 4) that this is suspected of being done without the modern sophisticated ribosomal molecular machinery within a cell:
"Thus, it seemed reasonable to speculate that the first polynucleotide molecule was initially an RNA polymer that was able to convey genetic information as well as organize amino acids into specific sequences to make proteins.

This article, published in 1962, was probably the first statement to suggest that RNA was the fundamental nucleic acid involved in the origin of living systems." [p. 11]

"These statements were published over 40 years ago. Today we have a wealth of information that strengthens the role of RNA in the early evolution of life. The discovery of ribozymes by Cech and the more recent discovery of micro-RNAs that have a variety of functions in controlling the development of biological systems suggests that these may be trace evidence of what has been called the "RNA world", meaning an era in early evolution in which RNA played a dominant role in both replication and in carrying out a number of chemical modifications leading to the organization of present-day biological systems." [p. 12]
(The Genetic Code and the Origin of Life, PDF, emphasis added). The graphic, above right (Viruses: Dead & Alive?), shows ~14 billion years of abiotic and biotic evolution, while depicting viruses as bridging the gap from the abiotic realm into the biotic realm  (cf. The Uncertain Gene - 9).

The next post in this series is here, the previous post in this series is here.


  1. "Using our "mind's eye", our imagination, can we place ourselves inside the world which was on Earth in an epoch that evolutionary scientists say existed prior to the time when carbon-based life forms first appeared?"......YES !