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.

Notes
[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.

References

• Lane, N. (2015) The Vital Question. Profile Books, London. Paperback edition (2016), 360 p.
• Lane, N., and W. Martin (2010) The energetics of genome complexity. Nature 467 pp.929-934.