Small Things Considered

May 22, 2015 9:04 PM

Carl Zimmer writes for The New York Times: How Simple Can Life Get? It's Complicated - "Scientists have long wondered how much further life can be stripped down and still remain alive. Is there a genetic essence of life? The answer seems to be that the true essence of life is not some handful of genes, but coexistence."

Snug as a ... Bug In A Bug In A Bug

How Does Tremblaya princeps Get Essential Proteins from Its Nested Partner Moranella endobia in the Mealybug Planoccocus citri?

How Many Genes Can Make a Cell: The Minimal-Gene-Set Concept, Koonin EV, Annu Rev Genomics Hum Genet. 2000;1:99-116.
Essential genes of a minimal bacteriumJohn I. Glass, 425–430, doi: 10.1073/pnas.0510013103
Essence of life: essential genes of minimal genomes. Juhas M, Eberl L, Glass JI., Trends Cell Biol. 2011 Oct;21(10):562-8. doi: 10.1016/j.tcb.2011.07.005. Epub 2011 Sep 1.
From essential to persistent genes: a functional approach to constructing synthetic life

A central undertaking in synthetic biology (SB) is the quest for the ‘minimal genome’. However, ‘minimal sets’ of essential genes are strongly context-dependent and, in all prokaryotic genomes sequenced to date, not a single protein-coding gene is entirely conserved. Furthermore, a lack of consensus in the field as to what attributes make a gene truly essential adds another aspect of variation. Thus, a universal minimal genome remains elusive.

posted by the man of twists and turns (28 comments total)

Man I love me some carl zimmer, but his op-ed's conclusions don't follow his premises at all. This is some meaningless purple prose:

Studies like Dr. McCutcheon’s show that the concept of a minimal genome, while provocative, is ultimately a dead end. Life does not exist in a laboratory vacuum, where scientists can pare away genes to some Platonic purity

BULLSHIT. Just because efficient co-operation in the wild has resulted in fit, small-genomed organisms that are interdependent, doesn't mean that there can't be an independent organism with a minimal genome.

If a "numinous nonsense" gene has been co-operatively selected for in the NYT op-ed writers population, bring on the Cas9-enabled deletions............. please.
posted by lalochezia at 9:18 PM on May 22, 2015 [7 favorites]

PS the co-operative gene-organism stuff is fascinating, and great science, and I wish he hadn't pissed in the (gene?) pool of otherwise great science with this rah-rah let's all fuckin' kumbaya twaddle distort-o-matic pullquote
posted by lalochezia at 9:20 PM on May 22, 2015 [3 favorites]

Unless Tremblaya and friends came into being on the sixth day of Creation, or else sprang complete from the head of Zeus, the concept of a minimal genome seems rather suspect to me. If there was a natural, chemical, origin of life (and I presume there was) then the "first living things" that reproduced and began evolving into more complex forms must have started out pretty darn simple. To know how simple life can be, in principle, I wager that the easiest approach is to create it from scratch.

Searching for a "minimal genome" by knocking out genes from living organisms is like trying to discover the smallest universal Turing machine by cutting wires in your laptop.
posted by brambleboy at 10:12 PM on May 22, 2015 [13 favorites]

That said, I nevertheless find these organisms and these studies to be absolutely fascinating.
posted by brambleboy at 10:15 PM on May 22, 2015

Searching for a "minimal genome" by knocking out genes from living organisms is like trying to discover the smallest universal Turing machine by cutting wires in your laptop.

No, it's more like quines and self-hosting compilers.
posted by sebastienbailard at 11:01 PM on May 22, 2015 [4 favorites]

I think the concept of a minimal genome can be coherent: a set of information and means of realizing instructions that result in physical changes, and harvesting of an entropic gradient to produce energetically unfavorable structures, consistent with replication and possible mutation of the information set. By this (wide) definition, animals, viruses, viroids, memes, and computer viruses all have minimal genomes. Prions are capable of conveying information by conformation and they can mutate conformation, but never make anything that is energetically disfavored (the same argument can be made to exclude fire as a living thing rather than an autocatalytic reaction).

The concept that is incoherent is self-sufficiency, which is highly contextual, i.e. dependent on the environment. To a plant, animals are not self-sufficient. To an animal, an obligate parasite isn't self sufficient. To the parasite, a virus isn't self-sufficient. It's obviously an analog continuum of "self sufficiency" without obvious graded steps. Does harvesting energy from sunlight confer some hidden virtue compared to harvesting energy from volcanic H2S vents, or blood? Which is more self-sufficient, a leech, a mosquito, or malaria? These are not useful arguments that will result in insight.
posted by benzenedream at 11:39 PM on May 22, 2015 [12 favorites]

At the other end of the spectrum, Daphnia.
posted by Segundus at 11:57 PM on May 22, 2015 [2 favorites]

A new physics theory of life

England’s theory is meant to underlie, rather than replace, Darwin’s theory of evolution by natural selection, which provides a powerful description of life at the level of genes and populations. “I am certainly not saying that Darwinian ideas are wrong,” he explained. “On the contrary, I am just saying that from the perspective of the physics, you might call Darwinian evolution a special case of a more general phenomenon.”
posted by a lungful of dragon at 1:06 AM on May 23, 2015 [2 favorites]

As an ecologist, I've never understood the strong desire to study organisms independent of the other organisms they actually evolved and live with. Without the bacteria that live in our guts, we will quickly die of malnutrition unless all the vitamins and amino acids we need are carefully manufactured for us in a lab. Does that make the human genome project not worthy of study? No, but it does mean that if you stop at the human genes in our bodies you do not really understand how our bodies work.
posted by hydropsyche at 4:01 AM on May 23, 2015 [8 favorites]

Just because efficient co-operation in the wild has resulted in fit, small-genomed organisms that are interdependent, doesn't mean that there can't be an independent organism with a minimal genome.

Yes it does. It's terrifically obvious: we are on a planet capable of supporting life, in a solar system that has been stable enough to not destroy our life-hosting planet, in a galaxy, universe, etc. so on and so forth.

Hate on kumbaya all you want but the reality is that the giant glowing orb that rises in the east every day is a reason you're alive. Life in other circumstances is adapted to its circumstances. In other words, it cannot be totally independent.

Tremblaya lives in one particular place: the body of a mealybug. And the mealybug, in turn, depends on Tremblaya for its survival.

The insect’s only source of food is the sap that it drinks from trees. On its own, the mealybug couldn’t survive on this meager diet. Tremblaya transforms the sap into vitamins and amino acids, which the mealybug can then use to build proteins. In exchange for this biological alchemy, mealybugs provide Tremblaya with a steady source of food and shelter.

There's also the sap-producing tree, that tree's environment...
posted by fraula at 4:59 AM on May 23, 2015 [2 favorites]

I think finding a minimal genome isn't as much as finding the origins of life as it is Code golf for biologists.
posted by ymgve at 5:17 AM on May 23, 2015 [2 favorites]

Life in other circumstances is adapted to its circumstances. In other words, it cannot be totally independent.

What have you got against libertarians? Sheesh.
posted by sneebler at 6:14 AM on May 23, 2015

Yes it does. It's terrifically obvious: we are on a planet capable of supporting life, in a solar system that has been stable enough to not destroy our life-hosting planet, in a galaxy, universe, etc. so on and so forth.


I think we have a different definition of "independent".

Of course living creatures we need energy and materials from the environment. No organism is an island. Of course, co-operative behavior by organisms is a winner, and of course, applying these concepts metaphorically to culture, society, behavior etc is a sensible and ethical thing to do (ain't no libertarian here.....)

What I wish to state is that just because deep-genome-metabolism-level co-operation is a fitness strategy that has worked, it doesn't follow that scientists can't make living organisms with a minimal, independent genome (that still needs 'fuel' but not much else)..... and then study life's mechanisms, and then harness that power to do Good Things.
posted by lalochezia at 6:27 AM on May 23, 2015

Oooooh! This is an easy one! The simpler the definition of life, the simpler life is.
posted by rankfreudlite at 9:26 AM on May 23, 2015

More in keeping with the context of the article, it is interesting to observe that mitochondria are thought to have been separate organisms, but were incorporated into cells and became integral.
posted by rankfreudlite at 9:37 AM on May 23, 2015

Looking at this think universally, consider computer programming; much of complex code is assembled from pieces of already-existing code. What other option is there? Imagine a neophyte programmer being told how a programming language works, then given an assignment to produce a computer operating system, something equivalent to iOS, for example. Impossible. The programmer would have to do as the article suggests: add things together. Although what I just described addresses one aspect of the process, it does not look at the larger picture. The larger picture is just an extension of Charles Darwin's work.
posted by rankfreudlite at 9:50 AM on May 23, 2015

You And Yeast Have More In Common Than You Might Think: "Genetically, at least, not that much has changed in the billion years since you two last shared a relative. Roughly half the 500 genes yeast need for life are interchangeable with the human versions."
posted by kliuless at 10:32 AM on May 23, 2015 [1 favorite]

"You And Yeast Have More In Common Than You Might Think"

Beer?
posted by Hairy Lobster at 11:36 AM on May 23, 2015 [3 favorites]

And malt does more than Milton can,
To justify God's ways to Man.
posted by Segundus at 12:22 PM on May 23, 2015 [1 favorite]

I have read fungal infections in humans are hard to cure because what poisons fungus, poisons us.
posted by Oyéah at 1:42 PM on May 23, 2015 [1 favorite]

Ahhhh LUCA, amore, not necessarily the simplest evolutionary tool in the shed, but a part of all living things. Supposedly this organelle is in the bacteria, in the bacteria.
posted by Oyéah at 1:55 PM on May 23, 2015

I have read fungal infections in humans are hard to cure because what poisons fungus, poisons us.

This comment warrants more than "favorited." It warrants "Worthy of further consideration."
posted by rankfreudlite at 2:02 PM on May 23, 2015

Fungal infections are harder to kill than bacterial infections because fungi have eukaryotic cells like ours, while bacterial cells are very different. Most antibiotics target specific things that are unique to bacterial cells. But fungal infections are no harder to kill than other eukaryotic infections, like malaria or parasitic worms.
posted by hydropsyche at 2:15 PM on May 23, 2015

Also, bacteria don't have organelles.
posted by hydropsyche at 2:17 PM on May 23, 2015

Fungal infections tend to be superficial in patients with a functioning immune system, which makes them relatively easy to treat, since you can use topical agents with low absorption that are too toxic to administer systemically. Systemic fungal infections (a major cause of death in immunocompromised patients) are a different story. There are a few systemic antifungals with a good safety profile, like the echinocandins and some of the azoles. But then you have a drug like amphotericin B, which is just terribly toxic, and wouldn't really be used at all if it wasn't so effective. Or flucytosine, which is basically just a prodrug of the chemotherapy agent 5-FU, with all the nasty toxicities you might expect.
posted by dephlogisticated at 3:24 PM on May 23, 2015 [3 favorites]

Fungal infections tend to be superficial in patients with a functioning immune system, which makes them relatively easy to treat, since you can use topical agents with low absorption that are too toxic to administer systemically. Systemic fungal infections (a major cause of death in immunocompromised patients) are a different story. There are a few systemic antifungals with a good safety profile, like the echinocandins and some of the azoles. But then you have a drug like amphotericin B, which is just terribly toxic, and wouldn't really be used at all if it wasn't so effective. Or flucytosine, which is basically just a prodrug of the chemotherapy agent 5-FU, with all the nasty toxicities you might expect.
To simplify this comment: fungal infections are simple but, when they get out of hand, they are not. Some medicines to treat the later example work well, others do not, because, while treating one sickness, they introduce another.
posted by rankfreudlite at 4:13 PM on May 23, 2015

Sure, lots of proteins are highly conserved between humans and yeast. The critical point is how the expression of those proteins are controlled.

The intricate cocktail of different growth factors that even the really simple nematode (roundworm) express in complex patterns that vary over time are even more complicated and regulated in more complex organisms.

The sequences that people point to and shout about being "junk" DNA - most of it is serves a regulatory role. Sure, at one point certain kinds of sequences might have been rendered "junk" but even some of those might end up being useful or actually "junk" and just filler. Some of those, though, end up being acknowleged as 3D modifiers that regulate the expression of genes from that unit of DNA through spatial regulation.
posted by porpoise at 8:14 PM on May 23, 2015

The sequences that people point to and shout about being "junk" DNA - most of it is serves a regulatory role.

I am a researcher in a lab that is part of the ENCODE group that made that claim, that most of the non-coding genome (across all observed species, generally) is regulatory. We put out a bunch of papers in September 2012 about this subject.

There are questions about this claim, some from evolutionary biologists who have noted the paradox of having so much "functional" DNA that should be responsive to selection pressure — if you mutate these regions, there should be some natural selection going on. Yet, if you do conservation analysis, there is a big disparity between how relatively little of the genome is conserved and how much ENCODE calls functional. Some criticisms of our work have been unsparingly brutal, though this largely hinges on a subset of biologists' definition of "functional".

My problem with the evolutionary biologists' arguments is that their definitions are pretty narrow and don't seem to take into account just how redundant a genome is, as a whole. A set of functional elements could cause a stem cell to differentiate as needed to some tissue of interest, and just knocking one out doesn't "kill the patient". So selective pressure exists, but you can have a lot of "junk" genome to mutate before you see a selection effect. I think Doolittle offers an interesting suggestion: Look at very large genomes, like those of certain fish and plants that have genomes three orders larger than that of human, and do experiments to mutate the "junk" DNA to see how much stays functional.

Still, knocking things out and getting down to a "minimal, working genome" in more complex organisms seems like a very difficult problem because of that redundancy. Incidentally, this is a huge part of why pharmaceutical companies can spend billions of dollars doing drug trials that end up going nowhere — you find a regulatory target that looks like it might be statistically interesting based on larger structural DNA features (so-called "chromatin structure", or how DNA opens up and compresses down), but using a drug to dial down a target or turn it off altogether can end up not doing much because some other part of the genome opens or closes at the right time and can remain functional. Or the drug ends up only working in some small subset of patients based on genomic variation that is very difficult or impossible to suss out from background noise — there's just too much data to look through.

One of the next steps is to build tools for creating and exploring regulatory networks that can be experimentally validated. Our lab is using TALENs to knock out these functional elements and see what happens to the interactions between and expression of genes. We might not get down to a "minimal genome" with respect to the human genome, but we may get closer to knowing more about what parts of the genome have critical functional roles, which will have huge payoffs for life science, particularly in designing targeted disease therapies.
posted by a lungful of dragon at 12:39 PM on May 26, 2015