“Horizontal gene transfer is more common than thought”: that's the message of a nice article in Aeon. I first came across it via a tweeted remark to the effect that this was the ultimate expression of the selfish gene. Why, genes are so selfish that they’ll even break the rules of inheritance by jumping right into the genomes of another species!
Now, that is some trick. I mean, the gene has to climb out of its native genome – and boy, those bonds are tough to break free from! – and then swim through the cytoplasm to the cell wall, wriggle through and then leap out fearlessly into the extracellular environment. There it has to live in hope of a passing cell before it gets degraded, and if it’s in luck then it takes out its diamond-tipped cutting tool and gets to work on…
Wait. You’re telling me the gene doesn’t do all this by itself? You’re saying that there is a host of genes in the donor cell that helps it happen, and a host of genes in the receiving cell to fix the new gene in place? But I thought the gene was being, you know, selfish? Instead, it’s as if it has sneaked into a house hoping to occupy it illegally, only to find a welcoming party offering it a cup of tea and a bed. Bah!
No, but look, I’m being far too literal about this selfishness, aren’t I? Well, aren’t I? Hmm, I wonder – because look, the Aeon page kindly directs me to another article by Itai Yanai and Martin Lercher that tells me all about what this selfishness business is all about.
And I think: have I wandered into 1976?
You see, this is what I find:
“Yet viewing our genome as an elegant and tidy blueprint for building humans misses a crucial fact: our genome does not exist to serve us humans at all. Instead, we exist to serve our genome, a collection of genes that have been surviving from time immemorial, skipping down the generations. These genes have evolved to build human ‘survival machines’, programmed as tools to make additional copies of the genes (by producing more humans who carry them in their genomes). From the cold-hearted view of biological reality, we exist only to ensure the survival of these travellers in our genomes... The selfish gene metaphor remains the single most relevant metaphor about our genome.”
Gosh, that really is cold-hearted isn’t it? It makes me feel so sad. But what leads these chaps to this unsparing conclusion, I wonder?
This: “From the viewpoint of natural selection, each gene is a long-lived replicator, its essential property being its ability to spawn copies.”
Then evolution, it seems, isn’t doing its job very well. Because, you see, I just took a gene and put it in a beaker and fed it with nucleotides, and it didn’t make a single copy. It was a rubbish replicator. So I tried another gene. Same thing. The funny thing was, the only way I could get the genes to replicate was to give them the molecular machinery and ingredients. Like in a PCR machine, say – but that’s like putting them on life support, right? The only way they’d do it without any real intervention was if I put the gene in a genome in a cell. So it really looked to me as though cells, not genes, were the replicators. Am I doing something wrong? After all, I am reliably informed that the gene “is on its own as a “replicator” – because “genes, but no other units in life’s hierarchy, make exact copies of themselves in a pool of such copies”. But genes no more “make exact copies of themselves in a pool of such copies” than printed pages (in a stack of other pages) make exact copies of themselves on the photocopier.
Oh, but silly me. Of course the genes don’t replicate by themselves! It is on its own as a replicator but doesn’t replicate on its own! (Got that?) No, you see, they can only do the job all together – ideally in a cell. “When looking at our genome”, say Yanai and Lercher, “we might take pride in how individual genes co-operate in order to build the human body in seemingly unselfish ways. But co-operation in making and maintaining a human body is just a highly successful strategy to make gene copies, perfectly consistent with selfishness.”
To be honest, I’ve never taken very much pride in what my genes do. But anyway: perfect consistent with selfishness? Let me see. I pay my taxes, I obey the laws, I contribute to charities that campaign for equality, I try to be nice to people, and a fair bit of this I do because I feel it is a pretty good thing to be a part of a society that functions well. I figure that’s probably best for me in the long run. Aha! – so what I do is perfectly consistent with selfishness. Well yes, but look, you’re not going to call me selfish just because I want to live in a well ordered society are you? No, but then I have intentions and thoughts of the future, I have acquired moral codes and so on – genes don’t have any of these things. Hmm… so how exactly does that make the metaphor of “selfishness” work? Or more precisely, how does it make selfishness a better metaphor than cooperativeness? If “genes don’t care”, then neither metaphor is better than the other. It’s just stuff that happens when genes get together.
But no, wait, maybe I’m missing the point. Genes are selfish because they compete with each other for limited resources, and only the best replicators – well no, only those housed in the cells or organisms that are themselves the best at replicating their genomes – survive. See, it says here: “Those genes that fail at replicating are no longer around, while even those that are good face stiff competition from other replicators. Only the best can secure the resources needed to reproduce themselves.”
This is the bullshit at the heart of the issue. “Good genes” face stiff competition from who exactly? Other replicators? So a phosphatase gene is competing with a dehydrogenase gene? (Yeah, who would win that fight?) No. No, no, no. This, folks, this is what I would bet countless people believe because of the bad metaphor of selfishness. Yet the phosphatase gene might well be doomed without the dehydrogenase gene. They need each other. They are really good friends. (These personification metaphors are great, aren’t they?) If the dehydrogenase gene gets better at its job, the phosphatase gene further down the genome just loves it, because she gets the benefit too! She just loves that better dehydrogenase. She goes round to his place and…
Hmm, these metaphors can get out of hand, can’t they?
No, if the dehydrogenase gene is competing with anyone, it’s with other alleles of the dehydrogenase gene. Genes aren’t in competition, alleles are.
(Actually even that doesn’t seem quite right. Organisms compete, and their genetic alleles affect their ability to compete. But this gives a sufficient appearance of competition among alleles that I can accept the use of the word.)
So genes only get replicated (by and large) in a genome. So if a gene is “improved” by natural selection, the whole genome benefits. But that’s just a side result – the gene doesn’t care about the others! Yet this is precisely the point. Because the gene “doesn’t care”, all you can talk about is what you see, not what you want to ascribe, metaphorically or otherwise, to a gene. An advantageous gene mutation helps the whole genome replicate. It’s not a question of who cares or who doesn’t, or what the gene “really” wants or doesn’t want. That is the outcome. “Selfishness” doesn’t help to elucidate that outcome – it confuses it.
“So why are we fooled into believing that humans (and animals and plants) rather than genes are what counts in biology?” the authors ask. They give an answer, but it’s not the right one. Higher organisms are a special case, of course, especially ones that reproduce sexually – it’s really cells that count. We’re “fooled” because cells can reproduce autonomously, but genes can’t.
So cells are where it’s at? Yes, and that’s why this article by Mike Lynch et al. calling for a meeting of evolutionary theory and cell biology is long overdue (PNAS 111, 16990; 2014). For one thing, it might temper erroneous statements like this one that Yanai and Lercher make: “Darwin showed that one simple logical principle [natural selection] could lead to all of the spectacular living design around us.” As Lynch and colleagues point out, there is abundant evidence that natural selection is one of several evolutionary processes that has shaped cells and simple organisms: “A commonly held but incorrect stance is that essentially all of evolution is a simple consequence of natural selection.” They point out, for example, that many pathways to greater complexity of both genomes and cells don’t confer any selective fitness.
The authors end with a tired Dawkinseque flourish: “we exist to serve our genome”. This statement has nothing to do with science – it is akin to the statement that “we are at the pinnacle of evolution”, but looking in the other direction. It is a little like saying that we exist to serve our minds – or that water falls on mountains in order to run downhill. It is not even wrong. We exist because of evolution, but not in order to do anything. Isn’t it strange how some who preen themselves on facing up to life’s lack of purpose then go right ahead and give it back a purpose?
The sad thing is that that Aeon article is actually all about junk DNA and what ENCODE has to say about it. It makes some fair criticisms of ENCODE’s dodgy definition of “function” for DNA. But it does so by examining the so-called LINE-1 elements in genomes, which are non-coding but just make copies of themselves. There used to be a word for this kind of DNA. Do you know what that word was? Selfish.
In the 1980s, geneticists and molecular biologists such as Francis Crick, Leslie Orgel and Ford Doolittle used “selfish DNA” in a strict sense, to refer to DNA sequences that just accumulated in genomes by making copies – and which did not itself affect the phenotype (W. F. Doolittle & C. Sapienza, Nature 284, p601, and L. E. Orgel & F. H. C. Crick, p604, 1980). This stuff not only had no function, it messed things up if it got too rife: it could eventually be deleterious to the genome that it infected. Now that’s what I call selfish! – something that acts in a way that is to its own benefit in the short term while benefitting nothing else, and which ultimately harms everything.
So you see, I’m not against the use of the selfish metaphor. I think that in its original sense it was just perfect. Its appropriation to describe the entire genome – as an attribute of all genes – wasn’t just misleading, it also devalued a perfectly good use of the term.
But all that seems to have been forgotten now. Could this be the result of some kind of meme, perhaps?