Tag Archives: genome


We can micro-miniaturize electronics by making their components smaller and smaller, but what about living organisms? Humans consist of over 20,000 genes coded into a billion-nucleotide molecule called DNA. That’s a lot of information for a complex organism like humans, but when it comes to genome size, a rare Japanese flower, called Paris japonica, is the current heavyweight champ, with 50 times more DNA than humans. But what is the smallest number of genes and nucleotides needed to create a living system?

Researchers call this the Minimal Genome, and it is what you get when you take a simple organism and strip away all of the non-essential and duplicative genes, leaving a bare minimum behind to spawn a healthy living system. To find one of these organisms in Nature, one would think that you have to search far and wide to find it among the millions of organisms on Earth. Luckily, a prime candidate was found much closer to ‘home’!

Following an intense multi-decade search, the current champion organism with the fewest naturally-occurring genes is a rather dangerous pest called Mycoplasma genitalium (M. genitalium). MG is a sexually-transmitted disease  that doctors have known about since the 1980’s and more than 1 in 100 adults have it. It causes urethritis and pelvic inflammatory disease among other symptoms. It is also a bacterium with only 482 genes among 582,970 nucleotides.

By 2008 the researchers had artificially synthesized the complete 482-gene, circular chromosome of M. genitalium, however, M. genitalium is a slow-growing bacterium so by 2010 the research switched to another simple organism called M. mycoides with a faster reproduction cycle. They were able to synthesize the 1-million nucleotide DNA of this bacterium and transplant it into the body of yet another bacterium called M. capricolum, which had been scrubbed of all its DNA. The new genome quickly took over the cell and was dubbed Synthia, but it behaved exactly as M. mycoides even though it was entirely synthetic. It had been created from a computer record of its sequential gene compliment and a set of chemicals, so it truly was the first lifeform whose parents were a computer and a set of chemical pumps!

Syn 3.0 – (Credit: Mark Ellisman/National Center for Imaging and Microscopy Research)

Following a tedious process of trial-and-error where over 100 different analogues with different minimal DNA sets were created, most non-viable, the creation of a new synthetic bacterium, Syn. 3.0, was announced by Nobel laureate Ham Smith, microbiologist Clyde Hutchison, and genomics pioneer Craig Venter at Harvard University in the journal Science on March 25, 2016.

Although Syn 3.0 only had 473 genes, amazingly, the function of 149 of these remains unknown. Some create proteins that stick out from the bacterium’s cell wall but their functions are unknown. Other genes seem to be involved in creating proteins that shuttle molecules in and out of the bacterium’s cell wall, but the nature of these molecules and their role in the cell’s metabolism is unknown. The artificial genome was also reorganized using a computer algorithm to place similar genes near each other – like de-fragging a hard drive, but this did not have any obvious effect on the bacterium.

In at least one case, a ‘watermark’ sequence was inserted into the genome of an earlier synthetic bacterium called M. laboratorium. The 4 watermarks are coded messages in the form of DNA base pairs, of 1246, 1081, 1109 and 1222 nucleotides respectively, which give the names of the researchers, and quotes from James Joyce, Robert Oppenheimer, and an especially relevant one by Richard Feynman: ‘What I cannot build I cannot understand’.

Is M. Genitalium really the smallest organism? Probably not, but it depends on how you define such minimal organisms. Since its genome was sequenced in 1999, we now know of five additional bacteria with even smaller genome sizes. The smallest of these is Candidatus Hodgkinia cicadicola Dsem with only 169 genes, however like the others this organism’s genome is supplemented by the host cell’s genome so it acts more like an organelle than a free-standing organism.
 M. genitalium is classified as an intracellular parasite and cannot exist by itself in the biosphere. It requires a host system such as the human urinary tract to provide the environment to sustain it. For truly free-standing organisms that can actually live by themselves and reproduce, the smallest of these is currently thought to be Pelagibacter ubique, which was found in 2002. It makes up 25% of all bacterial plankton cells in the ocean. It also undergoes regular seasonal cycles in abundance – in summer reaching ~50% of the cells in the temperate ocean surface waters. Thus it plays a major role in the Earth’s carbon cycle! Its genome was sequenced in 2005 and consists of 1,308,759 nucleotides forming 1,389 genes. Its genome has been streamlined by evolution so that it requires the least amount of nitrogen to reproduce (a scarce resource in the bacterium’s ocean environment). The base pairs C and G are nitrogen-rich, with a total of 11 nitrogen atoms between them. A and T are nitrogen-poor and have only 7 nitrogen atoms between them. All other environmental factors being equal, instead of 50% of the genome containing A and T, a whopping 70% does. Somehow, this bacterium has found a way to find alternative ways to create genes that are essential for life by avoiding the ‘expensive’ alternatives. Over billions of years it optimized itself to the current low-nitrogen compliment.

Why is all of this important? Why is synthetic genomics such an important research area? Because it is a direct way to identify how hundreds of genes work together to create viable living systems: their skeletons, metabolisms and reproductive strategies. For astrobiologists, it is a glimpse of what alien life might look like when it is pared down to its absolute essentials but still behaves as an independent system rather than a viral symbiont requiring a pre-existing host. Also, once we know what a basic viable bacterium host looks like, genetically, we can systematically add to this genome other factors of interest to us. We can explore what the process of epigenetics looks like as various environmental factors are added to switch on and off genes. Above all, it is the inevitable questions to come about the essential mechanism of life that will be the most exciting to watch develop!

Check back here on  Tuesday, June 6 for the next essay!