And the Genomes Keep Shrinking…

Here are a few numbers about DNA–some big ones, and then some very small ones.

The human genome contains about 3.2 billion base pairs. Last year, scientists at the University of Leceister printed the sequence out in 130 massive reference-book-sized volumes for a museum exhibit. From start to finish, they would take nearly a century to read.

A typical gene is made up of a few thousand bases. The human genome contains about 21,000 genes that encode proteins. There are other genes in the human genome that encode molecules known as RNA, but how many of those RNA molecules actually do anything useful in the cell is a matter of intense debate. A lot of the human genome is made of neither protein- or RNA-coding genes. Much (maybe most) of it is made up of dead genes and parasite-like stretches of DNA that do little more than making copies of themselves.

As I wrote recently in the New York Times, 3.2 billion base pairs and 21,000 genes are not essential requirements for something to stay alive. E. coli is doing very well, thank you, with a genome about 4.6 million base pairs. That’s .14% the size of our genome. Depending on the strain, the microbe has around 4100 protein-genes. That’s about a fifth the number of protein-coding genes that we carry. The high ratio of genes to genome size in E. coli is the result of its stripped-down, efficient genetics. Mutations that chop out non-functional DNA spread a lot faster in microbes than in animals.

E. coli, in turn, has proven to be positively gargantuan, genetically speaking, compared to some other species. As scientists explore more of the microbial world, they find species with smaller genomes. In my column for the Times, I wrote about the record-holding tiny genome, belonging to a microbe called Tremblaya. Its genome is a mere 139,000 base pairs. That’s .004% the size of our genome. You could print the entire sequence in a single slim paperback you could slip in your pocket. And in that sleek genome are just 120 protein-coding genes–.6% of our own collection of protein-coding genes.

Whenever I report on such record-breakers, I try to stress that they are only breaking records at that moment. Tremblaya has the smallest genome known. Or, I should now say, it had the smallest genome known last month.

This month in the journal Genome Biology and Evolution, Gordon Bennett and Nancy Moran describe a new record holder, called Nasuia deltocephalinicola. It has a genome of just 112,000 base pairs. Imagine taking that slim novella and ripping off the last chapter. Ironically, Nasuia packs in more genes into its DNA than Tremblaya–137 protein-coding genes, Bennett and Moran estimate.

What’s really striking about all these current and former record-holders for small genomes is that they all live in a single exotic ecological niche. Without exception, they can be found inside plant-feeding insects. Tremblaya lives in mealy bugs, for example, while Nasuia lives in a leafhopper (Macrosteles quadrilineatus).

Inside those hosts, these microbes carry out chemical reactions on the food that the insects eat. The insects feed on sap and other fluids from plants, which contains few nutrients. But the bacteria can use the compounds floating in the fluid to build amino acids, which the insects can then assemble into proteins.

Leafhoppers, cicadas, sharpshooters, and other related insect species carry related versions of the same stripped-down bacteria. By drawing their evolutionary trees, Bennett and Moran have found that the insects got into a symbiotic relationship with the microbes over 260 million years ago. I’ve reproduced their tree below for those who want some gory details. The blue lines show Nasuia and related lineages of microbes. The insects also acquired another species of bacteria, known as Sulcia. Together, these two microbes split the work for millions of years. (In some insects, fungi also jumped into the mix.)

The ancestors of Nasuia started out as free-living microbes that had genomes on par with E. coli. But once they got inside a host, they were able to lose DNA without paying a price. The insects gave them a stable home, building special organs to shelter them, and they even pass down the bacteria to their offspring. The bacteria cast aside many genes that might otherwise seem essential, such as a number of genes involved in generating energy. All they needed to do was continue to provide a service, by synthesizing some amino acids.

Nasuia holds the record now, but probably not for long. There are many other species of insects left to investigate. Moran had John McCutcheon of the University of Montana have done some back-of-the-envelope calculations to figure out how much smaller the genomes of those symbionts can get. All known insect symbionts share 82 genes in common. It’s possible those genes are absolutely required to survive as a symbiont. But a symbiont also needs to provide a benefit to its host, or its host will likely get rid of it. It takes at least 11 genes to synthesize a single amino acid. Those 93 genes, McCutcheon and Moran estimate, could fit in a genome as small as 70,000 base pairs.

It’s funny that these bacteria allow us to probe one of the most basic questions about life: how simple life can get and yet still qualify as being alive? While those who make fun of science for a living may consider such research a waste of time, studying these stripped-down organisms is also about as practical as science can get. The leafhoppers that house Nasuia, for example, are a nightmare for farmers, causing damage to a wide range of vegetables by spreading fungi and bacteria. Yet they would be helpless if not for their exquisitely simple lodgers. If we can understand how they survive with such tiny genomes, we may be able to stop them from enabling their hosts.

From Bennett and Moran 2013
From Bennett and Moran 2013

14 thoughts on “And the Genomes Keep Shrinking…

  1. By the same criteria (of finding suitable hosts to carry out some of the essential features) I hold that viruses also qualify as alive.

  2. Great article! I wonder if mentioning the more traditional examples of Evolutionary masterpieces turning Parasitism into Commensalism/Symbiosis may not contribute to reinforcing your point of the direct relevance to society? Mitochondria, Chloroplasts, Azotobacter, Nitrobacter are all dependent host genes and residences while repaying hosts by meeting their energetics or synthetic needs. Several pathologies are now linked to mutations in Mitochondrial DNA.

  3. But at what point do these symbionts, who cannot survive without contributions form their host, cease to be alive and begin being part of the host itself?

    Our mitochondria can be considered highly integrated symbionts; they reproduce apart from the cell, provide us a very big benefit and have bacteria-like DNA.

    What if we find a bacterium that lacks the genes even to read its own DNA, relying instead on importing proteins from the host? What if we find a bacterium that cannot synthesize anything but a beneficial substance for its host? Do we have a working definition to draw aline in the sand, this side life, this side not? Do we even have a vague idea beyond ‘We know life when we see it?’

    This is why I only pay attention to the smallest feel-living genome. (And yes I have a definition for ‘free living’)

  4. Seeing as those tiny cellular genomes – you forgot the “cellular” – are of obligate symbionts that appear WELL on their way to being organelles, I think you have to consider viruses in your “smallest genome” stakes.

    And the smallest non-dependent viral genomes are less than 2000 bp – the circoviruses! More of which are being discovered every day, infecting everything from mammals to birds to who-nows-what, under the waves.

    1. See, now ssRNA viroids sound interesting as do circoviruses; both seem to be full of interesting biological tricks and have interesting lifecycles.

  5. I agree, viruses are living molecular organisms inside cells, viroid spores outside.

    Kudzu, if we need “free living” as opposed to co-evolving, parasites wouldn’t qualify as life.

    But these organisms are more interesting as examples of where independent lineages stops and dependent organelle lineages starts. As they still migrate with the egg instead of multiply within their target cells, they are symbionts rather than endosymbionts. Given time they may end up as the latter.

    These organisms don’t bear much on the rise of genomes leading up to the UCA anyway, since life started out without genes. But they interestingly demonstrate that even today’s cells don’t need much genes.

  6. It’s silly and pointless to debate what, exactly, is or is not alive … nature is not carved at the joints by our words.

    1. But if it is silly to debate life then it is equally silly to talk about the ‘essential requirements for something to stay alive’. Given that ‘life’ is inherent to this topic I think that arguing definitions has a place here.

      Aside from that the world’s smallest virus is also an interesting topic. It would be interesting to see something about it here.

  7. “If we can understand how they survive with such tiny genomes, we may be able to stop them from enabling their hosts.”

    It bothers me that when people feel compelled to defend biological research, they almost always cite its potential to produce a better way to kill. Is life not interesting? Does learning about it not enrich our way of being in the world? Don’t justify your curiosity about minimal genomes by an appeal to industrial applications, Carl Zimmer! Resistance to monoculture’s corrosive effect on biodiversity should come first from those in a position to appreciate biodiversity!

    [CZ: Practical applications flow from basic research. We just can’t predict in advance what those applications will be. While I appreciate biodiversity, it won’t make the leafhoppers stop eating carrots. Monoculture is a problem for many reasons, but even the most diversified farm can still be plagued by these insects. The fact is that basic research on the biology of these pests may offer some ways to fight them. Even organic farmers take advantage of microbiology by spraying the bacterial toxin Bt on their crops to kill insects.]

  8. I like to think of “life” as the set of reactions inherent to the replication of self-coding informational systems – of which biological organisms are a subset, by the way.

    And a subset that spans the range from blue whales to the smallest genomes capable of getting themselves replicated, which are the naked circular ssRNA viroids – at only 250-odd nucleotides for the smallest.

    The fact is, the only organisms capable of surviving by themselves on this (or probably any other) planet are those that can make ALL their own organic molecules from inorganic substrates, and get energy from chemical reactions not involving free oxygen – which is itself a product of life. Which means that only chemolithotrophs – like the ones found deep underground in solid rock – are truly independent lifeforms, as EVERYTHING else – to one degree or another – depends on the presence of other organisms and the products of their metabolisms.

    And viruses are just a special case, in that they are intracellular parasites that use host ribosomes.

    And yes, arguing over what constitutes “life” is a bit like the how-many-angels-on-the-head-of-a-pin debate – and equally pointless. To bend John Lennon’s famous saying, “Life is something that just happens while you argue over what it is”.

    1. I think debating what life is is an interesting activity in and of itself. Pretty much every concept we have, ‘death’ ‘consent’ ‘truth’ ‘species’ has no rigid well-accepted definition but that doesn’t make discussing possible definitions pointless.

      Do viruses live? Prions? Chemicals that catalyze their own production? There is much to be discussed and learned in such debates.

  9. “A lot of the human genome is made of neither protein- or RNA-coding genes. Much (maybe most) of it is made up of dead genes and parasite-like stretches of DNA that do little more than making copies of themselves.”

    According to evolution only necessary genes survive why does human genome have genes that are useless or bygone?

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