Coordin­a­tion Prob­lems in Evolu­tion: The Rise of Eukaryotes

Introduction

This is a series of posts about co­ordin­a­tion prob­lems, as they ap­pear in the course of bio­lo­gical evol­u­tion. It is based on the book “The Ma­jor Trans­itions in Evolu­tion” by John Maynard Smith and Eörs Szath­máry. Pre­vi­ous part, dis­cuss­ing Ei­gen’s para­dox as well as the ori­gin of chro­mo­somes, can be found here.

In this part we are go­ing to look at the ori­gin of eu­k­a­ryotic cell, spe­cific­ally at its ac­quis­i­tion of en­dosym­bi­otic or­gan­elles, and at the ori­gin of mul­ti­cel­lu­lar­ity.

Proka­ryota vs. eukryota

While all single-celled or­gan­isms may look like sim­ilar wig­gly little creatures to us, there is a huge dif­fer­ence between proka­ryota (like bac­teria) and eu­k­a­ryota (like pro­to­zoa or, for that mat­ter, our own cells). The cell wall is dif­fer­ent. The in­terior of the cell is dif­fer­ent. One has ri­gid cell wall, in the other it’s the cyto­skel­eton that holds the cell to­gether. One has a single-ori­gin DNA strand at­tached to the cell wall, the other has nuc­leus con­tain­ing chro­mo­somes. One has mi­to­chon­dria and chloro­plasts, the other does not. Even the mech­an­ism of cell di­vi­sion is dif­fer­ent. If we haven’t known that we share part of the gen­ome, it would be easy to make a mis­take and be­lieve that the life on Earth had ori­gin­ated at two sep­ar­ate oc­ca­sions.

The trans­ition from prokayotes to eu­k­a­ryotes is likely the most com­plex trans­ition in the en­tire course of evol­u­tion. It took two bil­lion years to hap­pen. More than the emer­gence of life it­self.

All that be­ing said, we are go­ing to look only at a single part of the evol­u­tion of eu­k­a­ryotes, namely at their ac­quis­i­tion of mi­to­chon­dria. Mito­chon­dria were free-liv­ing cells once. But then they’ve be­came an in­sep­ar­able part of eu­k­a­ryotic cell. Hence, back to the co­ordin­a­tion prob­lems!

How did it come to be that some cells star­ted liv­ing within other cells? Well, as­sum­ing that flex­ible cell wall and pha­go­cyt­osis evolved be­fore the do­mest­ic­a­tion of mi­to­chon­dria, get­ting them in­side wouldn’t be a big prob­lem. It hap­pens each time one cell eats an­other.

What’s more in­ter­est­ing is how did the guest cell sur­vive and how did the co­oper­at­ive be­ha­vior between the host and the guest evolve.

Symbiosis

Let’s make a di­gres­sion and think about sym­bi­osis for a second. If we as­sume that there are only two strategies for the host (cul­tiv­ate the sym­biont or try to kill it) and two strategies for the sym­biont (co­oper­ate with the host or para­sit­ize) then the prob­lem gets re­duced to vari­ants of the pris­oner’s di­lemma game.

Con­sider this kind of ar­range­ment of pay­offs. The num­bers spe­cify the fit­ness of the host (left) and the sym­biont (right):

It can be eas­ily seen that there is only one equi­lib­rium: Whatever the host does it’s bet­ter for the sym­biont to para­sit­ize. And if the sym­biont is a para­site it’s al­ways bet­ter for the host to kill it.

Under what con­di­tions do we see this kind of game? The au­thors point out that this hap­pens when each in­di­vidual host ac­quires some ge­net­ic­ally dif­fer­ent sym­bionts from the en­vir­on­ment. The reason is that it doesn’t pay for the sym­biont to in­vest in the co­oper­a­tion with the host if the host is go­ing to be killed by a dif­fer­ent sym­biont any­way.

How about a dif­fer­ent scen­ario?

The ideal strategy for the sym­biont is not clear in this case. If the host is cul­tiv­ator it may pay to the sym­biont to co­oper­ate. If, on the other hand, the host tries to kill it, the best thing for the sym­biont to do would be to mul­tiply as fast as pos­sible, re­gard­less to any dam­age to the host.

This kind of setup is ex­pec­ted if each host ac­quires only a single sym­biont from the en­vir­on­ment:

However, with hosts in­fec­ted by a single sym­biont, co­oper­at­ive mu­tu­al­ism is likely to be stable once it evolves. The evol­u­tion from para­sit­ism to mu­tu­al­ism will be favored if the hosts killing re­sponse is in­ef­fect­ive, and if the fur­ther spread of the sym­biont is greater if the host does sur­vive. It will not oc­cur if the host can rap­idly rid it­self of the para­site, or if the para­site spreads only by killing the host.

Fin­ally, let’s have a look at the the fol­low­ing scen­ario:

Again, there’s only one equi­lib­rium. It’s al­ways bet­ter for the sym­biont to co­oper­ate and once it’s co­oper­at­ing, it’s bet­ter for the host to cul­tiv­ate it.

This hap­pens when the host ac­quires one or a few sym­bionts from one of its par­ents.

It makes sense: If the only place you can dis­perse to are your host’s chil­dren you really don’t want to kill it.

So there’s a rule of thumb emer­ging here: If the trans­mis­sion of the sym­biont hap­pens between un­re­lated in­di­vidu­als (ho­ri­zontal trans­mis­sion) the sym­bi­osis will evolve to­wards para­sit­ism. If the sym­biont is passed only from one par­ent to its chil­dren, then the re­la­tion­ship will evolve to­wards mu­tu­al­ism.

In fact, both ex­per­i­ments and ob­ser­va­tions in the wild show that ver­tical trans­mis­sion of the sym­biont leads to mu­tu­al­ism and ho­ri­zontal trans­mis­sion leads to para­sitsm. There are some ex­cep­tions though. For ex­ample, the trans­mis­sion of lu­min­ous bac­teria in deep-see fish is ho­ri­zontal, yet the sym­bionts are es­sen­tial to the sur­vival of their hosts.

Para­sites or live­stock?

Now, let’s get back to the ori­gin of eu­k­a­ryotic cell. What was the re­la­tion­ship between the early host cells and early mi­to­chon­dria?

It may have been that the mi­to­chon­dria were para­sites. Maybe they some­times es­caped the host cell and in­fec­ted dif­fer­ent cells. However, the au­thors hint at an in­ter­est­ing al­tern­at­ive: The host cells may have farmed the mi­to­chon­dria for the later con­sump­tion, just like we do with the cattle.

One im­port­ant point to un­der­stand here is that, how­ever we feel about slaughter­ing cows, from the pop­u­la­tion gen­er­ics point of view it’s a mu­tu­ally be­ne­fi­cial ar­range­ment. Homo Sapi­ens gets steaks. Bos Taurus be­comes one of the most com­mon ter­restrial ver­teb­rates around.

So, the host cells may have first con­sumed mi­to­chon­dria, but then learned to keep them around (or rather in­side) so that they can be con­sumed later.

And we do see some evid­ence that the host cell ad­opts act­ive meas­ures to keep the re­la­tion­ship mu­tu­al­istic. In sexu­ally re­pro­du­cing spe­cies the trans­mis­sion of mi­to­chon­dria hap­pens from one par­ent only. When hu­man egg merges with hu­man sperm, all the mi­to­chon­dria from the sperm are dis­carded and only those from the egg make their way into the em­bryo. That, ac­cord­ing to the model de­scribed above, pre­vents com­pet­i­tion between the dif­fer­ent strains of mi­to­chon­dria at the ex­pense of the host cell.

Later on in the evol­u­tion, straight­for­ward con­sump­tion of the sym­bionts must have been re­placed by pro­tein “taps” that we see in­stalled into the cell wall of mi­to­chon­dria today. The taps al­low the nu­tri­ents pro­duced by the mi­to­chon­dria to flow into the host cell. Think of Maa­sai punc­tur­ing the flesh of a cow and drink­ing the blood without killing the an­imal. The fact that the tap pro­tein is al­ways en­coded in the DNA of the host cell rather than in mi­to­chon­drial DNA is a hint that the idea of the host cells “farm­ing” mi­to­chon­dria may not be that im­plaus­ible.

Gene trans­fer to the nucleus

Once the mi­to­chon­dria were liv­ing in­side the host cell a curi­ous pro­cess began. The genes from the mi­to­chon­dria star­ted “jump­ing” into the host cell’s nuc­leus.

By los­ing their genes, mi­to­chon­dria lost the chance to break free from the eu­k­a­ryotic cell for good. So why did it hap­pen? And who be­nefited?

I really like this pro­cess be­cause it shows how com­plex the in­ter­play between dif­fer­ent levels of se­lec­tion can be. In par­tic­u­lar, we have to do with three dis­tinct levels of se­lec­tion here: Selec­tion on the level of the host cell, se­lec­tion on the level of mi­to­chon­dria and se­lec­tion on the level of a single mi­to­chon­drial gene.

First, we can ima­gine a mi­to­chon­drial gene get­ting at­tached to a nuc­lear chro­mo­some. It would be clearly ad­vant­age­ous for the gene: One more copy! Hooray! What’s not to like?

But why didn’t the gene got dis­carded from the nuc­lear DNA given that it per­formed no use­ful func­tion? Well, it turns out that nuc­lear DNA can con­tain hu­mung­ous amounts of dead code and yet the code doesn’t get dis­carded by nat­ural se­lec­tion. Con­trast that with proka­ryotes which tend to keep their ge­netic code short, sweet and stream­lined.

But wait. The gene would still be trans­lated into pro­tein. That would be a use­less ex­pendit­ure of en­ergy and thus it would be se­lec­ted against. To make it ad­vant­age­ous for the cell there must have been a mech­an­ism to trans­port the pro­tein back into mi­to­chon­dria. Luck­ily, all that is needed for that is to add to the pro­tein a “transit pep­tide”, a handle which would be re­cog­nized by a re­ceptor in the mi­to­chon­drial mem­brane and used to carry the pro­tein in­side. Creat­ing such a handle is easy. Baker & Schatz pas­ted ran­domly chosen pieces of E. coli and mouse DNA in front of pro­tein genes, and found that 2.7 per cent of the bac­terial in­serts and 5 per cent of the mam­malian ones were suc­cess­ful transit pep­tides.

Another hint that the trans­ition may be easy is that there is no dis­tinct pat­tern to the transit pep­tides. In other words, the transit pep­tides prob­ably evolved 700 times in­de­pend­ently — once for each mi­to­chon­drial gene that was trans­ferred into the nuc­leus.

When the gene is in nuc­leus and the pep­tide handle in its place, the mi­to­chon­dria can gain ad­vant­age by dis­card­ing the genes that they don’t need any­more (they are im­port­ing those pro­teins from the out­side any­way). And, as already men­tioned, proka­ryotes are very good at strip­ping their gen­ome of any un­ne­ces­sary bag­gage. Nick Lane does some back-of-the-en­volope cal­cu­la­tions and con­cludes that the en­ergy sav­ings are truly huge.

All of that be­ing the case, the ques­tion is rather why all the genes haven’t been trans­ferred to the nuc­leus.

Why the gene trans­fer stopped

For mi­to­chon­dria, the pro­cess was stopped by the change in mi­to­chon­drial ge­netic code (see only kind-of-re­lated but fun-to-read column by Douglas Hof­stadter). As soon as one of the mi­to­chon­drial codons began cod­ing for a dif­fer­ent amino acid, the genes could no longer jump to the nuc­leus. When they did they were turned into de­fect­ive pro­teins by the old, un­mod­i­fied nuc­lear trans­la­tion ma­chinery.

But that can’t be the en­tire story. The chloro­plast genes are en­coded in the plain old gen­eric code. Yet the chloro­plasts still keep some of the genes for them­selves. This may (or may not) in­dic­ate that there’s still some level of sep­ar­ate iden­tity to the or­gan­elles, that they may have goals of their own not fully aligned with the goals of the en­clos­ing eu­k­a­ryotic cell. An ex­ample of that would be, for ex­ample, mi­to­chon­dria try­ing to dis­tort the sex ra­tio of the host spe­cies.

(As a side note, there are or­gan­elles called per­ox­i­somes that were once thought to be en­dosym­bionts, very much like mi­to­chon­dria. Ex­cept that they had no genes at all. It has been sug­ges­ted that they may be en­dosym­bionts that have trans­ferred all of their genes to the nuc­leus. However, that idea has been re­cently chal­lenged.)

Multicul­lu­lar life and Orgel’s second rule

Multi­cel­lu­lar life sure looks like it has a co­ordin­a­tion prob­lem. All those bil­lions and tril­lions of cells have to co­oper­ate some­how. Most of them have to give up in­di­vidual re­pro­duc­tion and rather work for the be­ne­fit of all. Hell, there’s even pro­grammed cell death where the cell is ex­pec­ted to will­ingly die when there’s no use for it any more.

But when you take a step back the ar­gu­ment doesn’t make sense. All those cells are ge­net­ic­ally identical. There aren’t mul­tiple en­tit­ies en­ga­ging in a co­ordin­a­tion prob­lem. There’s just one en­tity: The multi-cel­lu­lar or­gan­ism it­self.

Or is there?

It may be in­struct­ive to pause here for a while and do an ex­er­cise in evol­u­tion­ary think­ing.

Con­sider what hap­pens if a so­matic cell mutates.

The muta­tion may cause the cell to di­vide in un­reg­u­lated man­ner.

But there’s even more in­triguing pos­sib­il­ity: Ima­gine that a the cell mutates in such a way that it’s more likely to give rise to a germ cell. For ex­ample, a plant cell that would oth­er­wise pro­duce a leaf would give rise to a flower in­stead. By do­ing so it would lower the over­all fit­ness of the or­gan­ism: The plant would now have less leaves than what’s op­timal. However, at the same time the reneg­ade cell would in­crease its own fit­ness be­cause any pol­len or seed pro­duced by that flower would carry the mutated gene in­stead of the ori­ginal one.

So what do you think? Does the above make sense or does it not? Is it really an in­tra-or­gan­ism con­flict? Think about that. I’ll wait.

Smith and Szath­máry ap­proach the prob­lem by split­ting it into two parts.

First, they dis­cuss whether muta­tion that in­creases a chance of giv­ing rise to a gam­ete cre­ates an in­ternal con­flict and, con­sequently, se­lec­tion pres­sure for other cells to evolve a mech­an­ism to pre­vent such muta­tions. They con­clude that it doesn’t. After all, this is not much dif­fer­ent from when the muta­tion oc­curs in a germ cell. The child will be slightly ge­net­ic­ally dif­fer­ent from the par­ent, but that’s just how evol­u­tion works. If the child hap­pens to be more fit than the par­ent, it will even­tu­ally pre­vail in the com­pet­i­tion on the or­gan­ism level. If not so, the new strain will be elim­in­ated by the nat­ural se­lec­tion.

The second part of the ques­tion is what hap­pens if the mutant is ma­lig­nant, i.e. if it causes un­reg­u­lated cell pro­lif­er­a­tion. We call that can­cer. In that case, the au­thors con­clude, there will be an ac­tual se­lect­ive force to pre­vent, or delay, the ma­lig­nancy.

Have you got that right? If not so, don’t be dis­ap­poin­ted and think about Orgel’s second rule. The rule says: “Evolu­tion is cleverer than you are.”

If you want to re­mem­ber just one thing about evol­u­tion, Orgel’s second rule may be a good choice.

In fact, Smith and Szath­máry, as good evol­u­tion­ary bio­lo­gists, have the rule in­grained and con­clude the sec­tion by hedging their bets:

There is, there­fore, no reason to think that [spe­cific mech­an­isms dis­cussed in the book] evolved to sup­press cell-cell com­pet­i­tion. But the ques­tion is im­port­ant, and we do not re­gard our ar­gu­ments as de­cis­ive.

To be continued

In the fol­low­ing parts I will cover the ori­gin of sex and of so­cial spe­cies. In the end I am go­ing to spec­u­late about pos­sible par­al­lels between co­ordin­a­tion prob­lems in evol­u­tion and co­ordin­a­tion prob­lems in hu­man so­ci­ety.