Oddly Microbial: Ribocytes

by Marcia Stone

Michael Yarus’s book, the basis for this article.

Ribocytes, our 4-billion year old RNA ancestors, were quintessentially microbial, quite different though than modern cells which eventually out-divided most of these little creatures and probably ate the rest. But while they were here ribocytes ruled the world—inventing both the genetic code and protein synthesis during their reign. The fact that today’s organisms still depend on RNA to carry out fundamental biochemical processes proves how durable such ribocytic inventions were.

“The genetic code is an invention of the middle RNA period,” says Michael Yarus at the University of Colorado in Boulder in his book Life from an RNA World: the ancestor within. Once reproducible RNA sequences were in place, riboenzymes, or ribozymes, were developed and replication began in earnest. “The RNA world appears in its definitive form when RNA learns to replicate and, as a result, Darwinian evolution begins,” he adds.

The ribocyte’s next astounding feat was protein synthesis. A few billion years later, in 2010, researchers from the Yarus lab created a very small RNA molecule capable of catalyzing a key step of protein synthesis, thereby showing that RNA enzymes could have been far easier to make then anyone ever expected, says Yarus. “This lends credence to the idea that RNA could direct and accelerate biochemical reactions under primitive conditions.” It also helps confirm the long-held belief that the original ribosomes were RNA alone, able to perform all the reactions required to make proteins. RNA and proteins eventually co-evolved into ribonucleoprotein complexes in which proteins, because of their greater versatility, became the major catalysts.

Even some natural metabolite-sensing RNAs known as riboswitches appear primordial in origin, according to Ronald R. Breaker from Yale University. “A newfound class of riboswitches that sense the bacterial second messenger cyclic-diguanylate-monophosphate (c-di-GM) could be a modern manifestation of an RNA World signaling partnership,” says Breaker.

Moreover, because every cell in all domains living on the planet today has ribosomes, it is likely that the Last Universal Common Ancestor (LUCA) had them as well. “Thus,” Yarus adds, “it’s reasonable to conclude that the RNA world came before the invention of proteins and lies behind the root of the tree; before the time of LUCA.”

Ribocyte description: This diagram shows some minimal ribozyme activities logically required for a self-sustaining and self-replicating ribocyte. It assumes the following points: (1) A duplex RNA genome where both strands are replicated by the same ribozyme replicase. Duplex unfolding requires a ribozyme helicase, and a ligase for joining short (lagging strand) newly synthesized RNA fragments; (2) A separate RNA transcriptase to generate single strand transcripts from recognized start and stop signals within the genome. These transcripts fold into functional RNA molecules as shown; (3) A set of ribozymes (‘B group’ here) mediating all necessary ribocyte metabolic activities. The form of the ribocyte genome shown here is purely for schematic purposes; it could be depicted as existing in various forms, such as a set of associated short fragment duplexes. Source: Ian Dunn’s blog Biopolyverse.

“It is likely ribocytes were cells because being membrane-delimited is by far the most plausible way to maintain a coherent evolutionary identity,” explains Yarus who suspects they were small, spherical creatures with no internal membranes and little fine structure. The outer membrane could easily have been made of cosmochemicals, “amphipathic lipids which occur naturally in the universe and don’t require complex biosynthesis.” Furthermore, because of their immense genetic instability, it’s probable that RNA creatures “lived amid a blaze of evolutionary change.” But they were slow to divide—very, very slow. Relying on ribozymes to reproduce would have taken days, which is a much more leisurely pace than the minimal 10-20 minutes required by some of the fastest replicating modern cells.

Because they were slow to reproduce and genetically fragile, it’s unlikely that any surviving ribocytes will shoot out of a thermal vent or be discovered sunning themselves on a desert rock, according to Yarus. If some are still alive today, they’re probably hiding in niches secure from modern microbes—barren, untrammeled, and ancient as well as favorable to RNA creatures in other respects for example lower temperatures and slightly acidic waters that could help stabilize their genome.

”Cold oceanic depths would be a productive hunting ground for surviving ribocytes. Or, maybe we could find them on Mars. Mars was once wetter and warmer and early life might have withdrawn into one of its sub-surface reservoirs of liquid water.” Given the prodigious explosive impacts around the inner solar system, Yarus speculates that Martian ribocytes might even be “our own ancestors waiting for us to return home to a superficially frozen planet where life’s clock stopped long ago.”

Marcia Stone is a science writer based in New York City and frequent contributor to ASM’s Microbe magazine.




 

Comments

[marcia stone]

James Lake from UCLA just e-mailed me this and I think it's worth posting (he said I could):

"These are intriguing ideas from the RNA world and, it wouldn't surprise me if someday soon they will be tested using genomic data."

[Mark O. Martin]

Oh, and I adored the Blobel quote. I used to call membranes "The Tupperware of Life" to students, but I wasn't making fun: compartmentalization is one of the keys to living things, I think.

[Mark O. Martin]

Another post sure to excite my students in the Fall---kudos to Marcia (and Elio and Merry).

One of the challenging bits regarding both "life on other worlds" and "how life evolved here on Earth" is that we only have one example that seems pretty successful here and now to study.

Joshua Lederberg used to push for looking for "life as we do *not* know it." Not easy (I liked his 1960s suggestion of enrichment culture in the presence of many curies of 32P...which might enrich for things like Deinococcus in retrospect). Anyway, I am always on the lookout for "weird" biological facts that might shed light on these biophilosophical questions.

One of my favorites is the much-missed Tracy Sonneborn's "cortical inheritance" concept in Paramecium. That is, a prior structure is used as a "blueprint" for the new structure (you can see me shielding my eyes from the Intelligent Design people). I could see things like simple proteins or nucleic acid polymers acting in a similar fashion.

http://en.wikipedia.org/wiki/Cortical_inheritance

My best guess is that "early life" was pretty slow and inefficient. Or else it is still hiding out here on Earth, waiting for someone cleverer than yours truly to find it!

[Nathan Myers]

Homing in on the origins of cellular metabolism and replication (do I repeat myself?) evokes sharper questions about the timing of membrane origin. If the first membranes formed spontaneously from cosmogenic amphipathic lipids, they could be expected to predate RNA replication by what we normally think of as eons. Howsoever the first actually ancestral replicase came about, the feature that distinguishes it from its contemporaries (it would need at least one, no?) and predecessors would have to be its inclusion in a pre-existing closed membrane.

We must imagine these fragile bags of chemicals conjugating and splitting by mechanical agitation, much like soap bubbles. Perhaps the beginning of cellular life and Darwinian evolution would not be the chaotic RNA production in the open ocean, or even within the membranes, but the accumulation of lipids to extend this microenvironmnent -- or even of defenses against too-promiscuous conjugation.

In this sense, RNA, proteins, DNA, and all the rest are just the primordial membrane's way of making more membrane. That membrane has since succeeded in making quite a lot of itself.

Elio adds:
"Omnis membrana ex membrana." (Blobel 1980, http://www.pnas.org/content/77/3/1496.full.pdf)