Almost the entire genome is made up of protein-coding genes*.

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*In bacteria.

But seriously, don’t you hate it when you read a headline that makes some intriguing claim that you think is about humans, only to discover that the research in question was based on mice, or yeast, or a computer simulation?

________

Update:

Here is a good example.

Aggression As Rewarding As Sex, Food And Drugs, New Research Shows

New research from Vanderbilt University shows for the first time that the brain processes aggression as a reward – much like sex, food and drugs – offering insights into our propensity to fight and our fascination with violent sports like boxing and football.

The study was based on mice.


The Moral Instinct by Steven Pinker in the New York Times.

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In my experience in dealing with anti-evolutionists, the fundamental motivation for dismissing evolution is not its adverse implications for religion itself (real or imagined, depending on your view), but the sense (definitely imagined) that accepting evolution subverts any basis for morality. One can go around and around with an anti-evolutionist only to discover in the end that he or she is really arguing from a moral perspective: “A naturalistic approach cannot show why it is absolutely wrong to kill someone, only divine moral laws can, thus evolution is unacceptable and hence incorrect.”

In this regard, it was with much interest that I read the piece by Steven Pinker in the New York Times on The Moral Instinct.

Now, I am not a major advocate of evolutionary psychology. Many of the “just-so stories” that come out of that circle make me either roll my eyes or cringe, depending on the usually overblown ratio of strength-of-claim to quantity-of-data. On the other hand, I would not argue that the human brain and the behaviours it exhibits are somehow exempt from the evolutionary processes that apply to every other organ in every other living species. However, that is not to say that all behaviours are adaptive — far from it. I suspect that some behaviours are (or were) adaptive, and some are not and never were.

Speaking specifically of innate human behaviours that are (or were) adaptive, I prefer to think of them as a series of “rules” or “guidelines” that are supplemented by details from culture. Nature via nurture. Language is a good example, and one that I use with students. The ability to learn a language is innate. Which language one learns is cultural. These are inseparable.

I have long thought that morality is rather similar. There is an innate moral compass that all normal humans possess (e.g., “the golden rule”, known to biologists as the basis of reciprocal altruism), but many of the specifics of what constitutes “good” versus “bad” are filled in by culture. Pinker takes a similar view, although he (I think correctly) distinguishes between societal conventions and moral principles, the former of which are especially culturally malleable. He also notes five basic themes that comprise the moral sense: harm, fairness, community (or group loyalty), authority, and purity (see also Haidt 2007). The proportions and expressions of these may vary among cultures, but they are universally identifiable in human beings. I quite like this formulation as a useful way to think about the differences and unities in moral judgments among people.

Finally, and perhaps most importantly, Pinker points out that studying and even explaining morality does not destroy it: if anything, it may help us to behave morally in a more effective way by adding some rationality to the equation.

The article is excellent, and I recommend it very highly.


Huckabee is right for all the wrong reasons.

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Over at Pharyngula, PZ points to an interview with former Arkansas Governor and presidential hopeful Mike Huckabee. As a Canadian, I have long been amused by Huckabee for reasons you can see here. The prospect of this guy becoming president is unnerving, but then so is the fact that our neighbours saw fit to elect (or at least, not not-elect) Bush. Twice.

Here is what Huckabee has to say about evolution. I have omitted the bit about teaching non-scientific alternatives in science class that preceded it, because it’s too silly to repeat (he says “all views”, but presumably he means “one other view” only).

Because, frankly, Darwinism is not an established scientific fact. It is a theory of evolution, that’s why it’s called the theory of evolution.

He’s right. “Darwinism” — a term used mostly by creationists, but also historically (e.g., Wallace) and to an extent today (e.g., Dawkins), especially in Britain — refers to natural selection as a mechanism of evolution. And it is a theory. In science, a theory is an explanation for an observed or inferred condition of the natural world that is well established through multiple lines of empirical evidence (i.e., a fact). Darwin’s theory of natural selection is one explanation for the fact that species are related through descent, which in turn has been well established in science for well over a century on the basis of fossils, biogeography, embryology, morphology, and genetics. Darwinian natural selection is not the only available explanation, and therefore represents a subset of modern evolutionary theory. That natural selection happens is an established fact (witness antibiotic resistance), but what its role is in causing large-scale evolution remains a subject of discussion among biologists.

So “Darwinism,” in the sense of meaning that the majority of evolution occurs via natural selection, is indeed not an established fact, it is a theory. Huckabee’s words are correct, even if his intent is terribly muddled. Scientific theories explain facts. If there is no established fact, then there is no theory needed.

I invite Gov. Huckabee to read more about this in a recent paper that is freely available here.


Is most of the human genome functional?

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I first became interested in genome size because of its tie-ins with important evolutionary questions in which I was (and still am) interested, such as punctuated vs. gradual patterns, levels of selection, and adaptive vs. non-adaptive processes. What I didn’t realize was that one component of the question, the quantity of DNA that is non-functional (but not necessarily inconsequential) with regard to the phenotype of the organism, is such a hot-button issue. I had vague inklings at first that young-earth creationists would object to the idea of non-functional DNA — because God, as they say, don’t make no junk. (Why intelligent design proponents, who purport to take a strictly scientific view of the question, also assume that non-coding DNA cannot be non-functional remains unstated). And of course there has always been a persistent undertone in biology that non-coding DNA must be doing something or it would have been deleted. This latter view, which derives directly from a hardcore adaptationist approach, destroys the argument by creationists that “Darwinism” has prevented researchers from considering functions for non-coding DNA. Indeed, the main motivation for the early papers on “selfish DNA” was to counter this adaptationist assumption (Doolittle and Sapienza 1980).

Creationist nonsense about DNA does not surprise me. What has intrigued me much more is the debate among biologists about this, and the rather questionable claims, suppositions, and extrapolations that get made not just by the media but by various scientists themselves.

Take Francis Collins. He’s a major player in genome biology and led the charge by the public Human Genome Project. And yet, he makes claims that non-coding DNA may be present in the genome “just in case” it needs to be put to use in the future. This makes no sense from an evolutionary perspective. It would be tempting to attribute this to Collins’s adherence to the notion of theistic evolution, but in fact one can find this sort of fuzzy foresight argument being brought up by lots of authors. I suppose it’s just disappointing that there is not better communication between genome biology and evolutionary biology.

The case that frustrates me most is that of John Mattick. He of the worst figure ever is one of the primary promulgators of the view that scientists have overlooked possible function for non-coding DNA and that this is “one of the biggest mistakes in the history of molecular biology” that can only be corrected by a “new paradigm”, and so on. Basically, the argument seems to be that much of the non-coding portion of a given genome is involved in regulation and such. In the past, Mattick has refrained from pinning down an estimate of how much non-coding DNA he believes is functional, but his presentation of (extremely selective) data left little doubt that he considers more non-coding DNA to be correlated with greater complexity. But now we’re starting to get some more explicit and increasingly bold claims.

As Check (2007) pointed out in a news article in Nature,

Mattick thinks scientists are vastly underestimating how much of the genome is functional. He and Birney have placed a bet on the question. Mattick thinks at least 20% of possible functional elements in our genome will eventually be proven useful. Birney thinks fewer are functional.

Now consider this quote by Comings (1972), who was the first person to use the term “junk DNA” extensively (even before Ohno’s (1972) coinage appeared in print):

These considerations suggest that up to 20% of the genome is actively used and the remaining 80+% is junk. But being junk doesn’t mean it is entirely useless. Common sense suggests that anything that is completely useless would be discarded. There are several possible functions for junk DNA.

So, even if Mattick is right about 20% of the human genome being functional, which is considered a rather high estimate on the basis of available data, he still would be merely agreeing with the author of the first major discussion about junk DNA.

Now, I should point out that I do not have a vested interest in how much of the human genome is functional. 5%? Fine. 20%? Fine. 50%? Ok. I will go where the data indicate. My reason for rejecting the notion of “more complexity means more DNA” is comparative: I refer you to the “onion test” for a simple illustration. However, as readers of Genomicron already know, I find it rather irksome when people take any new finding about (potential) function in some part of the human genome and extrapolate this to mean that all DNA in every genome must be serving some role.

Anyway, back to what Mattick suggests. As noted, for the most part he has gone about arguing for large-scale function more by hint than by direct claim. However, finally he says the following (Phaesant and Mattick 2007).

Thus, although admittedly on the basis of as yet limited evidence, it is quite plausible that many, if not the majority, of the expressed transcripts are functional and that a major component of genomic information is rapidly evolving regulatory DNA and RNA. Consequently, it is possible that much if not most of the human genome may be functional. This possibility cannot be ruled out on the available evidence, either from conservation analysis or from genetic studies, but does challenge current conceptions of the extent of functionality of the human genome and the nature of the genetic programming of humans and other complex organisms. [Emphasis added]

It seems to me that “we can’t rule this out” is not a reason to think that something is plausible, let alone true. In fact, the existence of mechanisms such as transposable element spread and the pseudogenization of duplicate genes suggests that there is good reason to expect much (probably most) of the genome to be non-functional unless data show otherwise. Some TEs have taken on a function, some cause disease, some are merely benign or only slightly detrimental. The proportions of non-coding elements in each of these categories remain to be determined, but they are not all equally likely by default.

The question of which sequences are functional, and in what way, is one of the more contentious and therefore interesting ones in genome biology. On the one hand, new information from various sources including the ENCODE project indicates that much non-coding is transcribed, though it remains an open question whether this has to do with function or noise. On the other hand, a recent analysis has suggested that as many as 4,000 sequences within the human genome initially thought to be genes are not really genes after all (Clamp et al. 2007), bringing the total count down to around 20,000.

Some people, mostly creationists and strict adaptationists (strange bedfellows, I agree) desperately want the vast non-coding majority of eukaryote DNA to have a function. They latch onto any new discovery of function in some segment of the genome or another (or indeed, any mere restatement of what many authors have been saying since the 1970s) and consider their position supported. The rest of us will just have to wait and see.

________________

References

Check, E. (2007). Genome project turns up evolutionary surprises. Nature 447: 760-761.

Clamp, M., B. Fry, M. Kamal, X. Xie, J. Cuff, M.F. Lin, M. Kellis, K. Lindblad-Toh, and E.S. Lander (2007). Distinguishing protein-coding and noncoding genes in the human genome. Proceedings of the National Academy of Sciences USA 104: 19428-19433.

Comings, D.E. 1972. The structure and function of chromatin. Advances in Human Genetics 3: 237-431.

Doolittle, W.F. and C. Sapienza. 1980. Selfish genes, the phenotype paradigm and genome evolution. Nature 284: 601-603.

Ohno, S. 1972. So much “junk” DNA in our genome. In Evolution of Genetic Systems (ed. H.H. Smith), pp. 366-370. Gordon and Breach, New York.

Phaesant, M. and J.S. Mattick (2007). Raising the estimate of functional human sequences. Genome Research 17: 1245-1253.


News stories of interest.

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In keeping with my recent minimalist approach to the blog, here are some links to stories by others that I think you may find interesting.

US ‘doomed’ if creationist president elected: scientists (PhysOrg)

I think this is a great line:

“The logic that convinces us that evolution is a fact is the same logic we use to say smoking is hazardous to your health or we have serious energy policy issues because of global warming,” University of Michigan professor Gilbert Omenn told reporters at the launch of a book on evolution by the National Academy of Sciences (NAS).

Evolutionary idea
Scientists rally to explain and defend the cornerstone of biological study
(Houston Chronicle)

An interesting piece (especially given the venue), and I am happy to say that it makes a note of the new journal Evolution: Education and Outreach, which I hope you’re all planning to read.


Hype vs. content.

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I think I should clarify my position on the human evolution acceleration issue, because I don’t want my comments about nonsense in the press to be misconstrued as a rejection of the study. The basic theoretical arguments make good sense, and I am eagerly awaiting (peer-reviewed) commentary regarding the particular method and dataset. As far as whether I accept the possibility of recent selection among humans, allow me to start by showing three slides that I use in my section on human history. These were presented three weeks ago, before I knew anything about the Hawks et al. paper.



If the Hawks et al. study holds up by next fall, I will add some slides about it specifically, because I think it nicely brings together ideas about adaptive peaks, population size, and selection.

My problem, as noted, is with the hype in the press, most of it direct quotes of the authors. Over at evolgen, Hawks suggests that “Most [bloggers] seem to be reacting viscerally to the idea that evolution could ‘accelerate’ by as much as we claim. That’s a deficiency of theory and/or knowledge about human history, which we’re trying as hard as we can to make a dent in.”

Maybe so. But that’s not the case with me, as should be obvious from above. But let’s evaluate how well these authors are succeeding in clarifying misconceptions about human evolution.

“History looks more and more like a science fiction novel in which mutants repeatedly arose and displaced normal humans – sometimes quietly, by surviving starvation and disease better, sometimes as a conquering horde. And we are those mutants.”

Now imagine you’re not a biologist. Your concept of “mutant” is based on what you know from science fiction. And a scientist tells you that human history really did include stampeding hordes of mutants, right out of science fiction. Does this help you to understand that it is an *allele* that is a mutant, and what really happened is that some of us, though more than in the past, are descendants who carry these alleles?

 “Five thousand years is such a small sliver of time – it’s 100 to 200 generations ago,” he says. “That’s how long it’s been since some of these genes originated, and today they are in 30 or 40 percent of people because they’ve had such an advantage. It’s like ‘invasion of the body snatchers.’”

Again with the science fiction. I have absolutely no idea how allele frequencies changing *over many generations* by normal vertical inheritance is anything remotely like body snatchers.

“We found very many human genes undergoing selection,” says anthropologist Gregory Cochran of the University of Utah, a member of the team that analyzed the 3.9 million genes showing the most variation. “Most are very recent, so much so that the rate of human evolution over the past few thousand years is far greater than it has been over the past few million years.”

A few million years ago there we no humans. Six (or so) million years ago, there would have been one species that eventually branched into the lineage of which humans are currently the only representative, and the one of which chimps and bonobos are the only extant examples. The *rate* of allele frequency change may be the highest it has ever been, but these statements are unbelievably misleading.

“In the last 40,000 years humans have changed as much as they did in the previous 2 million years.”

Modern humans, as a species, have existed for about 200,000 years or so. More than 90% of the history covered in this claim includes Homo habilis and Homo erectus. Allele frequency changes *may* be faster and more abundant now than during all that time, but this is hardly as significant under the normal conception of “evolutionary change” as the actual origin of two new species, including our own.

Their paper may be great. What they have been stating about it is irresponsible.

Evolution with a bullet.

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There is a lot of buzz about the recent (but still unavailable [update: link]) PNAS paper by John Hawks et al. reporting an accelerated rate of natural selection in humans. This time, I am not going to pick on the media who, predictably, are selling this as a conclusive finding when those of us in the scientific community have not even had a chance to read the paper yet, let alone for anyone to try to critically assess it. It may be fantastic work, and if it holds up I will certainly give it a significant place in my lecture on human evolutionary history. My complaint is about what the authors themselves have been telling the press.

“Ten thousand years ago, no one on planet Earth had blue eyes,” Hawks notes, because that gene—OCA2—had not yet developed. “We are different from people who lived only 400 generations ago in ways that are very obvious; that you can see with your eyes.”

Interesting idea. But I suppose at no time in history could there have been another variant that caused blue eyes? Is this really the sort of thing that can only evolve once and in one way?

“We aren’t the same as people even 1,000 or 2,000 years ago,” he says, which may explain, for example, part of the difference between Viking invaders and their peaceful Swedish descendants.

Um, ok. I wonder if blue eyes make you peaceful?

Harpending says genetic differences among different human populations “cannot be used to justify discrimination. Rights in the Constitution aren’t predicated on utter equality. People have rights and should have opportunities whatever their group.”

And, by implication, the groups are not utterly equal. Care to speculate on which groups are more equal than which others?

The new study comes from two of the same University of Utah scientists – Harpending and Cochran – who created a stir in 2005 when they published a study arguing that above-average intelligence in Ashkenazi Jews – those of northern European heritage – resulted from natural selection in medieval Europe, where they were pressured into jobs as financiers, traders, managers and tax collectors. Those who were smarter succeeded, grew wealthy and had bigger families to pass on their genes. Yet that intelligence also is linked to genetic diseases such as Tay-Sachs and Gaucher in Jews.

No comment.

“History looks more and more like a science fiction novel in which mutants repeatedly arose and displaced normal humans – sometimes quietly, by surviving starvation and disease better, sometimes as a conquering horde. And we are those mutants.”

Michael Crichton’s latest: LACTASE, the harrowing story of a small mutation that conferred a slightly better ability to digest milk and reached a higher frequency in some human populations. Expect the movie in summer 2010.

“Five thousand years is such a small sliver of time – it’s 100 to 200 generations ago,” he says. “That’s how long it’s been since some of these genes originated, and today they are in 30 or 40 percent of people because they’ve had such an advantage. It’s like ‘invasion of the body snatchers.’”

Genes, alleles. Tomayto, tomahto. Either way, they’re out to take us over!

“We are always trying to outrun disease.”

And body snatchers.

“Natural selection cares about how many children you have. People will have kids younger and younger.”

Where’s Bart Simpson when you need him? Natural selection is not conscious. Natural selection is not conscious. Natural selection is not conscious. Natural selection is n…

“Genetic engineering will make all this irrelevant. If people want green-haired kids they will go to the doctor and get them in 100 years.”

No they won’t, because people will be marrying robots by then.

“We are more different genetically from people living 5,000 years ago than they were different from Neanderthals.”

MNSdfnklcn. Oops, sorry… that was Coke sprayed all over my keyboard.

“In the last 40,000 years humans have changed as much as they did in the previous 2 million years.”

Nxjbjbecbc. Dammit… again!

“We found very many human genes undergoing selection,” says anthropologist Gregory Cochran of the University of Utah, a member of the team that analyzed the 3.9 million genes showing the most variation. “Most are very recent, so much so that the rate of human evolution over the past few thousand years is far greater than it has been over the past few million years.” [emphasis added]

Really? A few million years ago there were no humans at all.


Authors use inappropriate terminology in "lower" paper.

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I know that many medically-oriented geneticists don’t understand even the basics of evolution, but do they have to make it so painfully clear?

Schlegel A, Stainier DYR. (2007). Lessons from “lower” organisms: what worms, flies, and zebrafish can teach us about human energy metabolism. PLoS Genet 3(11): e199 doi:10.1371/journal.pgen.0030199

Some tidbits:

Recent studies using the worm Caenorhabditis elegans, the fly Drosophila melanogaster, and the zebrafish Danio rerio indicate that these “lower” metazoans possess unique attributes that should help in identifying, investigating, and even validating new pharmaceutical targets for these diseases.

…
As will be discussed below, unbiased methods have been used to identify more genes whose mutation in lower metazoans leads to phenotypes that are comparable to human syndromes of altered energy homeostasis like obesity.

…

Rather, studies on energy homeostasis in C. elegans, Drosophila, and zebrafish are proving that genetically tractable lower organisms can alter our understanding of the relationship of metabolic processes underlying obesity and its related illnesses (atherosclerotic vascular disease and type 2 diabetes mellitus).