Sunday, September 17, 2017

The Vital Question, by Nick Lane - Part 2

Mitochondrion. Source: US NIH
" So what about sex, or the nucleus, or phagocytosis? [...] If each of these traits arose by natural selection which they undoubtedly did and all of the adaptive steps offered some small advantage which they undoubtedly did then we should see multiple origins of eukaryotic traits in bacteria. But we don't. This is little short of an evolutionary 'scandal'. "
Nick Lane The Vital Question (2015)

In my previous post I commented on the first part of Nick Lane's book, which deals with the proton-motive force and the origin of life. This second post focuses on the second half of the book, which explores the origin of complex life (i.e. eukaryotic cells).

If the first half of the book was equally part history of the field and part new hypotheses, the second half leans clearly more towards hypothetical ideas albeit including many facts, and backed with rigorous thinking. Lane's big idea is the following. Most traits that differentiate eukaryotes from prokaryotes (cell and genome sizes, nucleus, introns, sexual reproduction) ultimately follow from a single and singular event: the endosymbiosis event that created mitochondria. For Lane, the organelles that power respiration in all eukaryotic cells are the one special ingredient that permitted the development of cellular complexity.

Thanks mostly to Lynn Margulis, we know now that at the origin of mitochondria lies the symbiosis of bacteria with an ancestor cell; the resulting 'symbiogenesis' gave birth to the eukaryotic cell. We do not know exactly who the ancestor cell was, although it is quite sure that it was more related to archaea than to bacteria (see for example this recent article by Eugene Koonin). What is puzzling, Koonin notes, is that comparative genomics indicates that the last common ancestor of all eukaryotes already possessed most of the signature traits of modern eukaryotes, including mitochondria, a nucleus, an endoplasmic reticulum and a cytoskeleton. You don't find intermediates between pro- and eukaryotes with just one or a few of those features [1]. Lane also points at this curious fact in his book (p. 43):

"But where did all these parts come from? The eukaryotic common ancestor might as well have jumped, fully formed, like Athena from the head of Zeus. We gain little insight into traits that arose before the common ancestor essentially all of them.[...] There are no known evolutionary intermediates between the morphologically simple state of all prokaryotes and the disturbingly complex common ancestor of eukaryotes. All these attributes of complex life arose in a phylogenetic void, a black hole at the heart of biology."

This is the 'evolutionary scandal' that Lane was alluding to in the quote opening this post. Can we stifle this scandal? Lane believes so. And the answer to the 'black hole at the heart of biology' could be the mitochondrion, and more particularly the energy gain that it represents for the cell, as Lane and his colleague Bill Martin proposed a few years ago (Lane & Martin, Nature 2010). Without this initial energy boost, there would have been no possibility to evolve those unique eukaryotic features, such as larger size and complex intracellular structures.

Take a cell's size, for example: the size of an eukaryotic cell is typically tens to hundreds of times larger than that of a prokaryotic cell. Why is it that bacteria do not form larger cells? Actually, some of them do: so-called giant bacteria exist, such as Epulopiscium fishelsoni (a long rod of 600 microns) and Thiomargarita namibiensis (a sphere almost 1 millimetre in diameter), but they are rare and grow slowly. They are also genetically very different from other bacteria in the sense that they show extreme polyploidy (respectively 200,000 and 18,000 genome copies in one cell!); these multiple genomes are not randomly distributed in the cell volume, but typically located close to the cell's membrane. As Lane and Martin suggest, this exteme number of genomes and their location is required to compensate for the extra size: genes required for energy production must be physically close to the membrane, hence if you have a vast volume and surface area, you need more copies of those genes (or genomes).

Mitochondria permit to eschew the problem faced by giant bacteria: a eukaryotic cell contains thousands of them (1-2,000 in a human liver cell, and up to 300,000 in some large amoebae), and all those mitochondria contain a small genome (16 kb) encoding 13 key proteins of the respiratory chains (but not all: others, including the ATP synthase, are encoded in the nucleus). In the evolutionary history of mitochondria, this suggests that most of the original endosymbiont genes migrated to the genome of the host cell, while a few key genes remained associated to the mitochondrion, forming a microgenome. To Lane, the maintenance of those genes is dictated by energetics: these genes need to be close to the bioenergetic membranes for them to function properly. When these genes are mutated (like in some mitochondrial diseases), this has serious consequences for respiration. To conclude, mitochondria (and their small genome) offer a solution to complexity that is unavailable to bacteria as well as giant bacteria. Lane notes (p.189):
"There is no benefit in terms of energy per gene from becoming larger, except when large size is attained by endosymbiosis."
This concept of 'energy per gene' is at the core of the argument made by Lane and Martin. Endosymbiosis (ancestor mitochondria) was the innovation permitting to vastly increase the energy supply available per gene in the cell. This paved the way for the expression of a wider variety of proteins, followed by the evolution of other eukaryotic traits. Much more is discussed in Lane's fascinating book, such as the evolution of introns and the nucleus, or the evolution of apoptosis, but I will not discuss it here.

I find Lane's ideas exciting and truly stimulating. It's important to note, however, that those ideas are not necessarily the final word on this discussion. Some biologists strongly disagree with the 'mitonchondrion-first' hypothesis for the evolution of complexity. Notably, Austin Booth and Ford Doolittle (PNAS 2015) at Dalhousie University (Canada), and Michael Lynch and Georgi Marinov (PNAS 2015) at Indiana University (USA). I let the curious reader discover for herself the arguments of these authors, as well as the rebuttal proposed by Lane and Martin (that you can find in the 'related content' of those articles). Scientific controversy and debate is doing well, and that's great news!

The Vital Question is definitely a read worth your time! But in any case, a good way to start is by watching the lecture that Lane gave as a recipient of the Michael Faraday Prize. This sums up his views nicely.

[1] One nuance can be brought here. As Lane reports, the group known as the archezoa were long thought to be such kinds of intermediates, since they do not possess mitochondria. However, mounting evidence suggest that archezoa derive from eukaryotes which lost mitochondria, not a missing link between prokaryotes and eukaryotes.


Sunday, July 09, 2017

The Vital Question, by Nick Lane

“In the end, respiration and burning are equivalent; the slight delay in the middle is what we know as life.”
This quote, from Nick Lane’s book The Vital Question (2015), is both poetic and true, which is the mark of great popular science writing. What Lane’s book attempts to do (and in my opinion succeeds in doing) is to radically change our perspective on life by showing us the crucial role played by energy. 

Lane is a biochemist at University College London and already the author of three books. I think there’s something to be said about popular science written by scientists, as opposed to science journalists, in the sense that they can sometimes achieve much more than educating. For example, they can fundamentally change our understanding of some topics (that certainly happened to me on some occasions). Actually, reading The Vital Question reminded me of reading Richard Dawkins’ The Selfish Gene many years ago, and Lane’s book did for me with biochemistry what Dawkins did with genetics and evolutionary theory: it opened a window into a fascinating new landscape. 

The universal proton-motive force
The Vital Question offers new glimpses into two of the most fundamental questions about life: why do all life forms use ion gradients to produce energy, and why eukaryotic cells are the way they are [1]. Now this is quite a programme! And Lane does a terrific job at presenting us with some of the best past and present ideas that were put forward in the field (including some of his own).
Regarding the first question, Lane writes (p. 65):  
“Life could have been driven by thermal or mechanical energy, or radioactivity, or electrical discharges, or UV radiation, the imagination is the limit; but no, all life is driven by redox chemistry, via remarkably similar respiratory chains.”
Peter Mitchell. Source:
In discussing the vital and universal role of the proton-motive force in living organisms, which generates ATP (the energy ‘currency’ in the cell)  thanks to a gradient of protons across membranes (see representation of ATP synthase below [2]), Lane pays tribute to Peter Mitchell, the Nobel laureate who first proposed the concept in the early 1960s, which he then called the ‘chemiosmotic hypothesis’.  I was very interested to learn about Mitchell, since as a biology student I was only introduced to the concept of proton-motive force, not to its history or its discoverer. And as Lane notes (p. 68), it was once called ‘the most counterintuitive idea in biology since Darwin’ by the biochemist Leslie Orgel.

Lane continues (p. 83):
“The evolution of chemiosmotic coupling is a mystery. The fact that all life is chemiosmotic implies that chemiosmotic coupling arose very early indeed in evolution.”
The ATP synthase. Image David Goodsell
In that context, I  was amazed to learn that fermentation, which I thought was some kind of ‘primitive’ way of obtaining energy, is most probably a more recent invention than the proton-motive force! (p. 168)

The origin of life
Lane delves into hypotheses on the origin of life with great detail in the second part of the book. It starts with the old ‘primordial soup’ theory that was first proposed by J. B. S. Haldane in 1929 and received support from the famous Miller experiment (published in 1953, the same year as Watson and Crick’s paper on DNA). Miller showed that organic molecules such as amino acids can be formed by the action of lightning on simpler gases like methane, ammonia and hydrogen. Life, the theory posits, would have evolved from those early organic bricks, after they were concentrated by evaporation of tidal pools or by adsorption to inorganic surfaces. As Lane notes, this theory is probably not true, and he explains that the favored explanations now involve deep-sea hydrothermal vents as primordial life incubators. This theory was prominently developed by Bill Martin and Mike Russell in the late eighties and in the nineties, and summed up in papers in 2003 and 2008

In particular, Martin and Russell have pointed at alkaline deep-sea vents as a possible original cradle for life. In such vents, they argue, exist unique geochemical conditions that could have been the biochemical template for the metabolism of the first living cells. For example, in these vents CO2 is abiotically reduced by H2 into methane (CH4), which is also the reaction that powers autotrophic prokaryotes known as methanogens. In addition, alkaline vents harbor strong pH gradients (i.e., proton gradients) between the alkaline interior and the more neutral seawater, as well as porous structures. And this brings us back to chemiosmotic coupling. Martin et al. note (2008): 
"Accordingly, it has been suggested that the ability to harness a continuous and naturally existing proton gradient at an alkaline hydrothermal vent is older than the ability to generate a proton gradient with a chemistry that is specified by genes. [...] Regarding the question of which came first, there are two simple possibilities: either energy-consuming pumping or energy-conserving chemiosmotic harnessing came first."
Martin and Russell favor the latter scenario. The reason why chemiosmotic coupling is universal in living organisms could thus be that early life evolved to use those preexisting proton gradients from deep-sea vents! This, however, is not necessarily how life came to be... But it is an exciting idea that deserves our full attention. As far as I'm concerned, it is still the best hypothesis for the origin of life that I have read.

In a follow-up post, I will write about the last part of the book that discusses the origin of complex (eukaryotic) life.

[1] Incidently,  it reminds me of that curious saying: ‘Science does not answer why questions, only how questions’. This is clearly untrue. Science often deals with ‘why’ questions, in particular questions pertaining to evolution. I’m not sure why this misleading saying persists, including among scientists…
 [2] Almost all cells use protons, but apparently some anerobic prokaryotic species use sodium ions instead.

  • Lane, N. (2015) The Vital Question. Profile Books, London. Paperback edition (2016), 360 p.
  • Martin, W., Baross, J., Kelley, D. and M. J. Russell. (2008) Hydrothermal vents and the origin of life. Nature Reviews Microbiology 6: 805-814.

Friday, March 17, 2017

Cooperation shapes the spatial patterns of bacterial organization

Cooperative bacterial strains colonizing a surface
Bacteria colonize surfaces in all environments. That could be the surfaces of soil aggregates, of rocks in a stream bed, of plant leaves, of animal skin, or that could be the surface of your showerhead... On such surfaces microbes establish complex communities ('biofilms') that can contain many different interacting species. These various species are usually not randomly distributed in the biofilm, but rather organized depending on their environmental preferences (for example some like well-aerated areas, others not so much...) and on the type of interactions that they have with each other. This can result in complex patterns of organization that manifest at the microscopic scale and up to the millimeter scale. Such patterns are not trivial, as they can sustain microbial activity and functions that would not be possible in a well-mixed environment, which has importance for biotechnology applications as well.

In a new study published this month, we examined the role of cooperation in shaping spatial patterns of bacterial organization on wet surfaces. The paper is available online and is entitled 'Cooperation in carbon source degradation shapes spatial self-organization of microbial consortia on hydrated surfaces'. Our idea was that a feeding dependency between two partners would directly control their distribution in space, hence imposing a specific pattern. We used a simple model system made of two bacterial strains that could grow using the chemical compound toluene (a hydrocarbon), but only when they were working together as a 'team' (a bacterial consortium in the jargon).