11 September 2005

Wake up, and smell the controversy

There are a pair of articles in this week's edition of the journal Science that are almost certainly going to cause some excitement and controversy in the field of human evolution. Controversies in this area are nothing new, of course, but these articles seem to have all of the necessary ingredients for a spirited debate. They also seem to be almost certainly destined to be miscited by any number of unsavory individuals.

Although the two articles have slightly different sets of authors, both come from the same laboratory, and both focus on the same topic: natural selection acting on genes involved in the development of the human brain. Two different genes were examined, and in both cases specific versions of the genes - alleles - were found to be present in frequencies that indicate that they have recently been (or still are) the subject of strong selective pressure. In both cases, the alleles appear to be very new - younger than the appearance in modern humans. Finally, and here is the bit that's going be the most controversial part of this, the selectively favored alleles are less likely to be present in people from certain geographic locales.

The first paper discusses the evolution of a the gene known as Microcephalin. This gene got its name because a lack of function in both copies of this gene causes a genetic disorder called microcephaly. Individuals suffering from microcephaly have brains that are extremely small, but which have normal structure.

The team of researchers had previously investigated the evolution of this gene within primates, and had noted that this gene appeared to have been the subject of strong positive selection in the lineage leading up to apes and humans. They report, in the Science article, that during the course of this study they noticed that one version (or allele) of this gene appeared to be very common in the humans that they had looked at. They also found that this version of the gene caused an amino acid change in the protein that it produces, due to a single mutation changing amino acid 314 from aspartate to histidine. This kind of thing is very exciting to people who do evolutionary genetics, so they decided to investigate further.

They looked at sequences for this gene from 89 different humans, with a wide range of geographic origins. They found that the region of the gene that they were looking at contained 220 different places where there were variations in the specific nucleotide ("DNA letter") at that position. They also found that there were 86 different alleles present in the population that they had examined. One of these alleles was extremely common compared to all the others. Out of the 178 copies of the gene (each person has 2 copies) that they looked at, 59 of them - 33% - were that one allele. 18 individuals were homozygous for that allele (meaning that both of their copies were that allele). The next most common allele was present in 11% of the copies.

That's the type of data that screams "selective pressure" the second you look at it. But it is possible to be more scientific about investigating it. One of the things that you can do is to use computer simulation to figure out what the probability is that you would see the same results if the allele frequency was the result of chance. The investigators used a set of very conservative estimates about human population dynamics, and ran the simulation 5,000,000 times. None of the simulations yielded the observed results. This is a very strong indication that the common copy of the allele is selectively favored.

The investigators also looked at the age of the allele and the geographic distribution. They found that the allele appears to be quite young (~37,000 years). They also found, and this is the part that is likely to stir up controversy, that the allele is much less common in sub-Saharan Africa than in the rest of the world. (It seems to be most common in populations from the Americas.)

The second article looks at the evolution of ASPM, which, like Microcephalin, is involved in the development of brain size. As in the first study, an allele was found to be present with a frequency far greater than one would expect if the allele was neutral. This allele turns out to be even younger than the Microcephalin allele reported earlier, with an estimated age of only about 5,000 years. It also shows an uneven geographic distribution. As you might expect, the younger allele is less widespread than the Microcephalin allele. It is most common in Eurasian and North African populations, and it is quite uncommon in Native American, sub-Saharan African, and some East Asian populations.

Two studies, both of genes involved in brain development, both demonstrating extremely strong indications that one allele has experienced very strong positive selection, and both indicating that the positively selected alleles are more common in Europeans than in most Africans. I suspect that these results are going to bring joy to what passes for the hearts of a number of slimebags. They shouldn't, but they will. They will because the pussbuckets in question are always willing to grab onto anything they think supports their narrow-minded beliefs with both hands. They shouldn't get excited because these results actually don't say anything about intelligence.

We don't actually know why those alleles have been selected. The genes are involved in the development of the brain, and in brain size, but the alleles could be favored for entirely unrelated reasons. It's possible, for example, that people with that version of the gene are less likely to suffer from some illness or another. Even if the alleles in question have been positively selected due to their effect on brain size, these are only two of a large number of genes that are involved in the development of intelligence. These two genes have favored alleles that are present in certain populations. Other genes may have favored alleles that are present in other populations.

These two studies should serve as an excellent reminder that evolution, even in humans, is a continuous and complex process. They should not serve as fodder for various fools and assorted idiots.

Follow up: In response to accusations from one of the people commenting on this post, I have put up, in a new post, a slightly more detailed explanation of why we need to be careful drawing conclusions from these studies.


References:
Evans, Patrick D et al. 2005. Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans. Science. Vol 309, Issue 5741, 1717-1720.

Mekel-Bobrov, Nitzan et al. 2005. Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens. Science. Vol 309, Issue 5741, 1720-1722.

16 Comments:

Anonymous Anonymous said...

pusbuckets

11:03 PM  
Anonymous Anonymous said...

NeoDarwinists are more creatures of politics than science. It's disgusting. It would be politically incorrect to infer that the human brain is still evolving and that some populations have alleles that are fitter than others. But this is the very core of what microevolution is all about. Chance mutations that improve fitness are selected by nature. Yet you deny it for political reasons. Shame on you for such dissembling.

-DaveScot

12:14 AM  
Anonymous vyoma said...

Thanks for providing further explanation. My wife, who is a cultural anthropologist, and I were discussing these findings a couple of evenings ago. Needless to say, her colleagues in biological anthropology are very excited abuot this study. I pointed out to her, as you point out here, that the study doesn't assign particular functions to the genes in question (apart from an allele of microcephalin being tied to microcephaly), so while the study is interesting from the POV of biostatistical data demonstrating ongoing evolutionary trends, making any judgment about the exact nature of those trends is premature. As is often the case, we know that something is happening, but exactly what's happening isn't a foregone conclusion.

This is something that DaveScot, by the way, appears not to comprehend at all. It isn't politically incorrect to point out that the brain is still evolving. In fact, it would be rather surprising if the major traits that have allowed humans to survive throughout the species' history WEREN'T evolving. What the specifics mean, though, isn't known. There may well be something in the environment in North America that isn't present in sub-Saharan Africa, for example, that has absolutely nothing to do with intelligence or any related thing. In fact, one can't make any judgment at this point as to the comparative worth of the extant alleles, since we don't know exactly what selective pressures the alleles address. It's entirely possible that the presence of an allele can make a population less fit in one environment but more fit in another, or even unfit in any niche over a given period of time until the allele eventually disappears. At this point, all we can say conclusively is that there are multiple alleles present at different frequencies in different populations. Political correctness has nothing to do with it; this is based on a lack of information, not the desire to promote and agenda.

12:59 AM  
Blogger ts said...

Does evolution not work in some geographic areas? Is intelligence required in some geographic areas but not others? It seems far more likely that there are differential environmental factors in the various regions which are applying selective pressure.

As for DaveScot, when it comes to those alleles that contribute to intelligence, he's deficient.

1:23 AM  
Anonymous Anonymous said...

The investigators used a set of very conservative estimates about human population dynamics, and ran the simulation 5,000,000 times. None of the simulations yielded the observed results. This is a very strong indication that the common copy of the allele is selectively favored.

Lets try to be clear. I do not think this is a major failing of the paper, but there is no such thing as a "very conservative" estimate of human population dynamics. They did test a range of demographic scenarios, but in fact they were fairly limited. The number of possibilities for demographic histories is enormous, and the effects of demography are one of the least well understood aspects of population genetics. In Drosophila there is currently a fair amount of controversy over the extent to which the observed variation across the genome is explainable by demography, or whether selection has to be invoked. The conclusions you draw are surprisingly sensitive to choice of parameters (time/severity of bottlenecks, etc).


Given this unknown, it is difficult to evaluate individual genes without reference to the rest of the genome. Lahn's lab looks pretty much exclusively at genes in the brain, so when they find a pattern that appears unusual, it will clearly be in a brain gene. Instant Science paper, instant controversy. What we do not know, however, is how unusual that pattern is in the genome. If 10%, or even 1% of the genome shows a similar pattern, it becomes more difficult to argue that any individual gene's pattern is the result of selection. Quite simply, these results are intriguing, but we do need an appropriate control in order to evaluate them properly.

2:48 AM  
Anonymous Mike Hopkins said...

A followup might be in order. Just how do they know that selection is the explanation of the gene frequencies. If there is no selection and the population is large enough to mimimize genetic drift one would expect that the gene frequencies would remain the same. However if our ancestors went through a genetic bottleneck, the gene frequencies could have been set by chance. And most of those involved in human evolution seem to think our ancestors did go through a few genetic bottlenecks. How do they rule that out as an alternative explanation of the observations?

Also how where the alleles dated?

3:15 AM  
Anonymous Anonymous said...

vyoma said:

"the study doesn't assign particular functions to the genes in question"

There doesn't seem to be much ambiguity here:

http://www.sciencemag.org/cgi/content/abstract/309/5741/1717?rbfvrToken=14f3dc82f7490145f35eb4b5ad86417263a80b20

Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans
Patrick D. Evans,1,2 Sandra L. Gilbert,1 Nitzan Mekel-Bobrov,1,2 Eric J. Vallender,1,2 Jeffrey R. Anderson,1 Leila M. Vaez-Azizi,1 Sarah A. Tishkoff,4 Richard R. Hudson,3 Bruce T. Lahn1*
The gene Microcephalin (MCPH1) regulates brain size and has evolved under strong positive selection in the human evolutionary lineage.

Denial is more than just a river in Egypt, Voyoma.

--DaveScot

3:19 AM  
Anonymous Dave Harmon said...

5K years ago is well into the age of city life, 37K is at least quite late in human development. (though apparently before the extinction of the Neanderthals)

My first question is: how does the second allele's prevalence differ between urban and rural populations?

(PS: don't feed the trolls!)

3:22 AM  
Anonymous Anonymous said...

ts

Obligatory tit4tat: Not as deficient as you.

Of course there's environmental pressure at work selecting for intelligence. It takes a lot more intelligence for a naked ape that evolved in a tropical climate to adapt to a temperate climate in a short timespan.

Like duh.

Watching you politically correct scientist/poseurs try to spin this is quite humorous.

--DaveScot

3:31 AM  
Blogger TQA said...

Mike (and others),

I'll try to do a follow-up on the more technical aspects of detecting selection at a single locus, and on how the age of the mutations was determined. It probably won't happen for a couple of days, though, since it's a pretty complex topic and it will take me a little while to make sure I understand it well enough to be able to explain it.

6:37 AM  
Blogger Ken Willis said...

The terms slimebag and pussbucket are new to me. Could you explain the scientific significance of these terms in your fine article. As a non-scientist I just want to be sure I understand these interesting concepts.

7:20 AM  
Blogger Apesnake said...

Feed the trolls. It exposes their poor table manners.

In that spirit: hello DaveScot.

Are you, by any chance a Discovery Institute shill who is being paid to post as a social Darwinist on sites which discuss biology in order to make evolution look like it is saying something it is not? Given the D.I. lack of anything approaching integrity I would not put it past them though I should hope they would get someone who sounds more believable as a real person. The reason I ask is that you use terminology that is directly taken from their playbook like "NeoDarwinists" and "microevolution" while displaying complete ignorance of real biological concepts like "fitness". If you have no connection with the Discovery Institute and are, simply a know-nothing know-it-all (a poseur as you put it) then I apologize for the insinuation (though not for the sentiment behind it).

While you are condemning people for being “politically correct” because they refuse to read as much in to a couple of research papers as you wish them to, might I ask you to consider that your personal definition of “fitness” might be more a product of your fantasy life than of reality.

DaveScot said:
”It would be politically incorrect to infer that the human brain is still evolving and that some populations have alleles that are fitter than others. But this is the very core of what microevolution is all about. Chance mutations that improve fitness are selected by nature. Yet you deny it for political reasons. Shame on you for such dissembling.”

Do you need to practice to be able to include so much garbage in one paragraph?

1)”It would be politically incorrect to infer that the human brain is still evolving…” No one (that I have read on this post) is saying that this is not what the papers are saying.

2)”and that some populations have alleles that are fitter than others.” If by politically correct, you mean wrong - then yes. If the alleles under discussion are fitter they will eventually replace all the other alleles. If they are fitter in some context they will come to a point in which their frequency is stable or fluctuates with changing environmental factors. Whether this happens or whether the selection pressure which is currently making them "fit" disappears is up to the natural principles of genetics, not whether you chose to label them as "more fit".

A)They found that the alleles in question were more frequent in some populations, not that they were present in some and absent in others.

B) Fitter in what way? An increase in intelligence is certainly one kind of fitness (assuming an environment where intelligence is actually an asset rather than something that will get you labelled as a dissembler or something which has you meet with the disgust of your unintelligent neighbours). So too is a trait which increases stupidity (for example making someone unable to understand when abstract concepts are explained to them) or which had a neutral effect on intelligence but which helped reduce childhood mortality or mitigated some unknown negative bi-product of adult lactose tolerance (another trait which has been under recent positive selection and is more common in European than Asian and African populations.

3) “ Yet you deny it for political reasons. Shame on you for such dissembling.” Your assumption that this “denial” is due to political reasons rather than an honest (if, in your mind, incorrect) appraisal of the issue is based on what… the desire to cast those who disagree with you as wussies? Please tell me you have something more than that. Refusing to jump to conclusions that are currently completely unsupported and giving alternate possible conclusions is not dissembling it is part of the scientific process. You would know that if you bothered to learn something about science instead of sitting around getting disgusted by it when it does not immediately jump out and give comfort to your pet theories (“cherry picking” from science being perilously close to “quote mining” which is a Discovery Institute copyrighted business practice). Shame on you for being a putz.

vyoma said:
"the study doesn't assign particular functions to the genes in question"

DaveScot said:
”There doesn't seem to be much ambiguity here:

http://www.sciencemag.org/cgi/content/abstract/309/5741/1717?rbfvrToken=14f3dc82f7490145f35eb4b5ad86417263a80b20

Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans”


The phrase “a Gene Regulating Brain Size” refers to Microcephalin. That is to say, for the gene in general not the allele which is under selective pressure, Gregor Mendel. How does a human with the new allele differ phenotypically from one with the many other older versions. You don’t know do you? You have assumed that it makes those who have it have larger brains and by necessity, (by what passes for logic in your world) have greater intelligence - haven’t you? Just out of curiosity, you do know that it is brain size is not the only factor influencing intelligence don’t you? You also know that genes can have more than one function and that these other functions can be selected for or against even if the “known” function might be the one we personally care about right?

DaveScot said:
Of course there's environmental pressure at work selecting for intelligence. It takes a lot more intelligence for a naked ape that evolved in a tropical climate to adapt to a temperate climate in a short timespan.

Like duh.

Watching you politically correct scientist/poseurs try to spin this is quite humorous.”


Everything you say is humorous DaveScot. Did you actually use the phrase “Like duh” or did some hacker edit you comment to make you look stupid? Please you script kiddies, DaveScot needs no one’s help in that area.
Like I mentioned, environmental pressures which select for intelligence are not the only ones there are. There is no reason to assume that any gene which is being strongly selected for is altering intelligence as opposed to any number of other traits which may or may not be brain related. Would a hypothetical increase in motor skills at the expense of reasoning skills which might allow better use of the tools of civilization be an improvement in intelligence? Judging by what you have typed that might be your opinion.

8:42 AM  
Blogger TQA said...

Ken:

One of the things I enjoy most about blogging is that I can say things the way that I see them. The language used was distinctly unscientific. The judgemental tone in that particular paragraph was unscientific. I discuss science here, but I don't feel compelled to use the same language that I would if this were, for example, a scientific journal.

But, on the other hand, sometimes it can be fun to phrase things in scientific language. If I were to revise this, I might write something like:

"Certain individuals may be prone for various reasons, including deficits in either the "nature" or "nurture" aspects of their development, to misinterpret these results. Such an outcome would not surprise this investigator, as there are always people who are willing to selectively misunderstand science in such a fashion as to support their political leanings. Such persons should be cautious in this case, for two reasons: first, the results of these studies give no indications as to the nature of the selective pressure on these alleles; and, second, becuase these alleles have not reached fixation in non-African populations, and they themselves might therefore be lacking this trait."

But I still like "slimebags" and "pusbuckets" better.

10:02 AM  
Blogger ts said...

DaveScot wrote:

"There doesn't seem to be much ambiguity here:

http://www.sciencemag.org/cgi/content/abstract/309/5741/1717?rbfvrToken=14f3dc82f7490145f35eb4b5ad86417263a80b20

Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans"

One could describe sugar as "a coffee sweetener" -- that would not be "ambiguous", but it also would not delineate sugar's functions.

"Obligatory tit4tat: Not as deficient as you.

Of course there's environmental pressure at work selecting for intelligence."

Since I didn't say otherwise, your greater deficiency is demonstrated by your failure to comprehend.

"It takes a lot more intelligence for a naked ape that evolved in a tropical climate to adapt to a temperate climate in a short timespan."

Naked apes? 5000 years ago? As for "tropical" to "temporate", you didn't pay much attention to the distributions actually reported -- as usual, your desired conclusion comes first, and all else is rationalization.

4:40 PM  
Anonymous Anonymous said...

ape snake

[yawn]

dumbass hoser

1:36 AM  
Blogger DavidB said...

Over the past two decades it has become a PC dogma that the genetic differences between human geographical population groups are minor and literally superficial, in the sense that they affect mainly surface characteristics such as pigmentation and the shape of the nose. I'm not going to give references, but just look at your well-thumbed copies of S.J. Gould.

Whatever else it means, this new research knocks that argument on the head. Genes that affect brain development have been shown to vary greatly in frequency between different geographical populations. This remains the case whether the genes have been selected directly for reasons of brain function, indirectly because of pleiotropic effects on other traits (e.g. disease resistance), or even if the frequency differences are not due to selection at all, but to genetic drift or founder effects.

12:59 AM  

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