Biology’s Dark Matter

Turns out that even in a genome stripped down to only those genes absolutely essential for human life, some 16% of the matter in there is completely mysterious to researchers in terms of its purpose or function. They know it’s there, they know it plays a role. They have no idea what that role is.

So, biology has dark matter just as the universe does. Like the universe, the genetic code of every living being is probably filled with it.

“We don’t know what they provide or why they are essential for life — maybe they are doing something more subtle, something obviously not appreciated yet in biology,” Venter told Science magazine. “It’s a very humbling set of experiments.”

In the Book of Genesis, the origin of life is handled this way:

And God said, “Let the earth sprout vegetation, plants yielding seed, and fruit trees bearing fruit in which is their seed, each according to its kind, on the earth.” And it was so.

As it happens, a pioneering group of researchers led by Clyde Hutchison out of Craig Venter’s lab in San Diego have targeted a tiny microbe that lives in cattle rumen, — as opposed to “vegetation”— to design life from the ground up. In this case, they produced a semi-synthetic life form — which is to say, they’ve injected DNA designed on a computer and injected it into a Mycoplasma species that was stripped of its genetic information — and voila, the organism boots up, divides and lives.

The original reports date back to 2010, when in a publication in Science, Daniel Gibson, Ph.D. and a team of 23 additional researchers outlined the steps to synthesize a 1.08 million base pair Mycoplasma mycoides genome, constructed from four bottles of chemicals that make up DNA.

At the time, according to Synthetic Genomics, “the process took 15 years to complete, and the 1.08 million base pair synthetic M. mycoides genome is the largest chemically defined structure ever synthesized in the laboratory.”

Then, Dr. Venter described the converted cell as “the first self-replicating species we’ve had on the planet whose parent is a computer. This is a philosophical advance as much as a technical advance.” In a television interview, he added: “It’s the next step. It’s a baby step, it’s a proof of concept that we can go from the computer into living cells, to control microbial systems to benefit humankind. It’s not for sale.” said Craig Venter.

What happened between then and now? Back then, the organism was basically a copy of the M. mycoides genome. Back then, it was an experiment to determine if the DNA could be produced on a computer, injected into an organism, and have the organism live and reproduce.

Now, the goal is to edit the genome down to the minimum number of genes for life.

So, last week in Science, the Venter team reported that they have brought down the number of genes to 473 — less than half of the number in the wild genotype, and the smallest number of genes yet found in any organism that can operate independently as life. This is M. mycoides JCVI-syn3.0.

You could call it, as Brad Pitt did  in Ocean’s Eleven, “the biggest Ella Fitzgerald ever”. As in the “Is it real, or is it Memorex?” commercials from the 1970s. In this case, maybe the smallest Ella Fitzgerald ever.

image by Tom Deerinck and Mark Ellisman.

The mysterious 79, and Dark Matter

One of the mysteries? Venter and team have identified 149 of these genes as being essential for life — without them, the organism dies — 70 the researchers can broadly classify as to function, but some 79 of them are a complete mystery.

That’s the Dark Matter.

The research remains controversial

Not everyone is thrilled with this path of research.

“My worry is that some people are going to draw the conclusion that they have created a new life form,” Jim Collins, a bioengineer at Boston University told the New York Times in 2010. “What they have created is an organism with a synthesized natural genome. But it doesn’t represent the creation of life from scratch or the creation of a new life form.”

The Times also quoted geneticist George Church knocking the announcement as “not necessarily on the path ” to creating useful microorganisms, while Caltech geneticist David Baltimore said that “Craig has somewhat overplayed the importance of this,” describing the achievement as a technical tour de force in scale, rather than a scientific breakthrough.

The Bioeconomy Impact

Venter said that a goal of Synthetic Genomics is to “build an entire algae genome so we can vary the 50 to 60 different parameters for algae growth to make superproductive organisms.”

Venter said back in 2010 hat the bacterium used for the proof of concept is not suitable for biofuels, but that the concept could be shifted to a more suitable candidate.

Brent Erickson, executive vice president for BIO’s Industrial and Environmental Section, added, “This scientific achievement could someday lead to the development of new microbes that could consume carbon dioxide and turn it into clean burning natural gas or that could efficiently clean up crude oil spills. The understanding of metabolic engineering gained by today’s research achievement holds great potential to open new avenues for research and development.”

Algae Algae oxen free

Well, the technology, if applied to algae any time soon (as opposed to bacteria, as in this advance), will bypass the oxen microbe route. But think of this as a base set of functionalities to which new genes would be added to

“In theory, we should be able to add genes back to [syn3.0] to recapitulate key parts of evolution,” Venter told Quanta magazine. “We could reduce billions of years of evolution to maybe years or months or weeks. We have one cell in production to make omega-3s more efficiently than it can be isolated from fish.”

But there’s a ways to go in terms of workload before replicating life on a grander scale. Humans have roughly a 18,000 gene set. Algae are in the 3,000-6,000 range.

But if you thought that humans were the most complex genetic life form, think again. The humble cottonwood tree has 45,000 genes. Rice has up to 50,000.

Next steps

Clearly, seeking understanding of the function of the dark matter — something outside of our current biological knowledge set.

Then, perhaps beginning to bridge the gap between this base organism with limited function in the real world — and, perhaps, the design of new functionalities from the base organism. The ability to produce a target molecule, for example — a fuel, a chemical. Or, the ability to change the inputs — for example, from photosynthesis to taking energy from an electric current, which can be supplied at far greater efficiency today through solar panels than photosynthesis. Perhaps, having the ability to tolerate salt water instead of using fresh water to make targeted products.

And on and on. Now that we’ve seen the tiniest Ella Fitzgerald ever, we’ll look forward to seeing what she can do.

More on the story.