Thursday, August 31, 2006

HAR1F: A hot new gene hits the scene

According to recent reports, scientists have identified a gene which has undergone an unusually rapid series of changes in the last few million years of human evolution. As the gene – assigned the catchy name HAR1F – appears to play a role in the development of the cerebral cortex, it may be one of the key genetic elements that make us smarter than the average bear – or horse, or chicken, or even chimpanzee.

The newly-discovered gene is unusual in a couple of ways: First, unlike “normal” genes – which are transcribed into messenger RNA which, in turn, controls production of a protein – HAR1F is an “RNA gene”: it produces an RNA string that functions on its own, affecting the organism directly rather than through creation of a protein product. But more importantly (for present purposes), HAR1F has undergone substantial changes in the course of human evolution over the last six or so million years, even though it’s a gene that normally changes very little over much longer time-spans.

The HAR1F gene is “essentially the same” in all mammals other than humans. Even between chimpanzees (our closest relatives) and chickens (who make good soup, but otherwise are not our friends), only two out of the gene’s 118 “letters” (more properly, “bases”) have changed – meaning that the gene has been almost entirely static for hundreds of millions of years. This is unsurprising: if the gene is significantly involved in fetal brain development, we would expect it to be conserved – since most possible mutations would be harmful or even fatal. How, then, do we explain the fact that human HAR1F differs from chimpanzee HAR1F in eighteen out of its 118 bases?

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One of the fundamental implications of Darwin’s evolutionary theory is that humankind is no longer to be viewed as something special, apart from the rest of creation. Instead, we are an animal descended from other animals; and our ancestors, while obviously of parochial interest to our not-so-exalted selves, are no more inherently God-like than those of shrimp or shrew. Even worse, modern Darwinism (as articulated, for example, by the late Stephen Jay Gould) tells us that evolution is not “directional”: there is no inherent drive for Nature to come up with “better” creatures over time, but merely random drift, periodic ecological catastrophe, and fortuitous survival of those creatures lucky enough to be in the right place at the right time with the right characteristics and something reasonably cute to mate with.

Obviously, this demotion of Man from “created in God’s image” to “ape descendant” is something that a lot of people find threatening – which may help to explain why Biblical fundamentalists spend so much time passionately fighting the teaching of evolution and yet often seem rather blasé about equally Biblical stuff like keeping the Sabbath and not coveting their neighbors’ asses. (Alternative explanation: a lot of people get all fired up about reading the Bible cover-to-cover, but get bored when they hit the “begats” after Noah’s Flood and give up; so they stick to the parts they know.) And even for those of us who intellectually embrace Darwinian evolution, it’s awfully hard to accept that our own species is ultimately just another bunch of animals enjoying its brief day in the sun until something wipes us out and we’re succeeded by our not-quite-human-in-our-sense-of-the-word descendants – or by something entirely different, like giant carnivorous land clams.

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I find it rather consoling, then, to think about HAR1F and its implications. It was already well known, of course, that we humans are inordinately proud of our intelligence. Our large brains are so important to us that:
  • they’re worth sacrificing a fair bit of our efficiency as bipeds (in that our pelvises need to accommodate an oversized birth canal, and thus are less than optimal for running away from giant carnivorous land clams, should such fearsome creatures evolve on our watch);
  • they’re worth having an almost uniquely difficult, painful, and dangerous childbirth process (with our only mammalian competitor for this title being the hyena, which has a whole different set of problems and motivations than we do);
  • and they’re worth spending some 22% of our metabolic resources on (meaning that we require a good bit more food than a normally-brainy animal our size would need; so if I’m so smart, how come I ain’t thin?)

HAR1F adds a strong molecular confirmation to these more subjective indications of human uniqueness: after at least 200 million years (and perhaps more than twice that) of nearly complete stasis, HAR1F all of a sudden started to change rapidly as one group of apes set out on the road to humanity. Of course, there is no reason to think that our ancestors’ HAR1F genes mutated more readily than anyone else’s; but for some reason, the benefits provided by some of the random changes that took place were enough to preserve them in our genome, while other species were content to stick with what had worked since before the dinosaurs.

Why was it worthwhile for our ancestors to play Russian roulette with a gene that every other species was afraid to touch? Why was it worth having all the cost and inconvenience of a large brain? If intelligence is such a good thing, why is human HAR1F the only one that differs from the usual sort?

It appears that there is something unique about us after all! Over hundreds of millions of years, animals have lived happily with brains that were perfectly adequate for finding food, for escaping from predators in order not to become food, for creating and raising offspring, and so on – but which would never swoon over a sonnet or solve a Sudoku, much less write a blog. If our fellow animals had a use for bigger brains, they would have them; after all, there is nothing at all inadequate about horses or herons, which are quite smart enough to live the lives they choose to live, even if they can’t comprehend James Joyce.

But our ancestors chose (or perhaps were forced into) a lifestyle in which a much higher degree of intelligence was crucial – so important that it was worth paying a uniquely heavy biological price. And the lifestyle changes must have started before our ancestors’ brain size began to skyrocket; otherwise there would be no evolutionary pressure selecting for ever-larger brains and ever-greater intelligence. As far as we know, this experiment has never been attempted before – at least not on this planet.

So what if we humans are not the Paragon of Creation, uniquely created in the image of God? We’re not just another bunch of animals either! We (or our progenitors) have gone down a path that no other Earthly lineage has ever traveled; we’ve paid a high price for unique strengths. Let HAR1F serve as a reminder of just how special we are, how new and unusual, with our oversized brains.

Now if we could only figure out how to use them!

(This post can also be found at the Guns and Butter Blog.)

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At Sat Sep 02, 12:40:00 AM GMT+3, Blogger TerraPraeta said...

I dunno. I would need to do some research, but my first thought: if HAR1F is that distinctly different in humans compared to other mammals (and indeed non-mammals) then I would suspect that our ancestors ran into a retro-virus. That big a change, probably back around the time of Lucy: it just makes sense.

Of course, that also takes away the 'specialness' again (as it should, IMO)


At Sat Sep 02, 11:48:00 AM GMT+3, Blogger SnoopyTheGoon said...

TP has a point there re specialness

"We (or our progenitors) have gone down a path that no other Earthly lineage has ever traveled;"

This still could be ascribed to a mutaion caused by change in radiation background, virus, ...

Whether we'll ever use that gift/curse of intelligence? Hmm... You tell me.

At Sun Sep 03, 01:56:00 PM GMT+3, Blogger Don Radlauer said...

I'm afraid TP and SnoopyTheGoon have slightly missed the point.

The question here isn't whether the changes in (pre-)human HAR1F came from some special source such as a retrovirus. The "specialness" I'm talking about is the fact that our lineage had a use for mutations in this gene (among others), while other lineages didn't.

While it's certainly theoretically possible that our line just "got lucky" in encountering the right retrovirus, the fact that 300,000,000 or more million years of evolution left this gene essentially unchanged in such a wide range of species indicates not that mutations didn't happen, but that they almost certainly did happen and were eliminated because they cost their organisms more than they benefited them.

If we look at the difference between our human genome and a chimpanzee's, we see that only a few regions show substantially different DNA. Were our evolution "special" simply because of background radiation, we'd see a difference in the overall mutation rate - particularly in the "junk DNA" segments that don't code for anything and thus can be permitted to mutate without creating non-viable organisms. But in fact, our DNA has been about as stable as you'd expect, except for the HAR1 region and a few others.

The fact that our lineage had so much need for increased intelligence that it was "willing" to tolerate the inevitable downside of preserving mutations in key brain-development genes is indeed "special". Otherwise we have to explain why over so many millions of years, no other lineage has retained an altered HAR1F gene: either we have to believe that the requisite mutations never happened at all except in our line, or we have to posit some other semi-miraculous reason that only we possess strongly-altered HAR1F.

The explanation that requires the fewest unsupported assumptions is that HAR1F mutates more or less as often as any other gene of its size; that as an important developmental gene for a key organ, mutant HAR1F is generally costly to an organism; that most organisms do not significantly benefit from even "beneficial" alterations in HAR1F because they have no particular use for increased intelligence; but that our lineage did benefit from some HAR1F mutations because our ancestors were already living a lifestyle that demanded a subtantial degree of intelligence, such that increased intelligence was worth paying a heavy biological price.

Note that this explanation does not require any major unsupported assumptions; it's consistent with what we know of current biology, evolutionary history, and the nature of our own ancestors. At the same time, it does mean that our lineage is "special" - in that it's the only one (as far as we know) in Terrestrial history that needed bigger brains so much that it was worth the functional/metabolic cost.

At Sun Sep 03, 11:34:00 PM GMT+3, Blogger TerraPraeta said...

I think you missed my point, Don.

You wote:

"This is unsurprising: if the gene is significantly involved in fetal brain development, we would expect it to be conserved – since most possible mutations would be harmful or even fatal. How, then, do we explain the fact that human HAR1F differs from chimpanzee HAR1F in eighteen out of its 118 bases?"

My suggestion of a retro virus answers this question. In most cases, as you say, a significant change in this gene would be fatal, so it is entirely probable that a single 'lucky' mutation accounts for the significant. By lucky, I mean both that the mutation was non-fatal AND useful to the organism in which it originated. From that point on, the gene (assuming continued adaptive benefit) would have been propogated throughout the gene pool. Considering that we are the only remaining homo species, it is not so surprising that no other animal has the same mutation.

"At the same time, it does mean that our lineage is "special" - in that it's the only one (as far as we know) in Terrestrial history that needed bigger brains so much that it was worth the functional/metabolic cost."

You could make this same claim of ANY adaptive trait in any family tree. You are singling out our big brain as if it is inherantly special. In fact, it is simply basic evolutionary theroy. Every adaption has a cost and a benefit. When the beneit outweighs the cost, then the trait is conserved.

Every lineage is uniqu and special: therefore none are.



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