Framing the Language Gene: FOXP2

You can now read the Krause et al (2007) paper from Current Biology regarding the FOXP2 variant found in Neanderthals in an open-access on-line form at Current Biology Online.

Here is the summary of the article:

Although many animals communicate vocally, no extant creature rivals modern humans in language ability. Therefore, knowing when and under what evolutionary pressures our capacity for language evolved is of great interest. Here, we find that our closest extinct relatives, the Neandertals, share with modern humans two evolutionary changes in FOXP2, a gene that has been implicated in the development of speech and language. We furthermore find that in Neandertals, these changes lie on the common modern human haplotype, which previously was shown to have been subject to a selective sweep. These results suggest that these genetic changes and the selective sweep predate the common ancestor (which existed about 300,000-400,000 years ago) of modern human and Neandertal populations. This is in contrast to more recent age estimates of the selective sweep based on extant human diversity data. Thus, these results illustrate the usefulness of retrieving direct genetic information from ancient remains for understanding recent human evolution.

The authors actually get more specific regarding the role of FOXP2 in language:

Although language and speech are clearly genetically complex phenomena, the only gene currently known that has a specific role in the development of language and speech is FOXP2. The inactivation of one FOXP2 copy leads primarily to deficits in orofacial movements and linguistic processing similar to those in individuals with adult-onset Broca's aphasia

While the paper by Krause et al is an important contribution because it involves allele-level comparison of nucleic genetic material between hominid groups and across living and extinct forms, the role of FOXP2 and the characterization of the genetics of language may be misleading, if not simply very very wrong.

The paper describes how nuclear DNA was recovered from Neanderthal material, and demonstrates that the FOXP2 variant found in modern humans is also present in this ancient material. The extraction process is very carefully done, there are piles of controls and checks for contamination and there is no particular reason to believe that the results are not real. However, these results are so sensitive from an interpretive perspective, and recovery of ancient DNA is so new, it is necessary to replicate this work with additional recovery attempts.

The authors conclude:

... the current results show that the Neandertals carried a FOXP2 protein that was identical to that of present-day humans in the only two positions that differ between human and chimpanzee. Leaving out the unlikely scenario of gene flow, this establishes that these changes were present in the common ancestor of modern humans and Neandertals. The date of the emergence of these genetic changes therefore must be older than that estimated with only extant human diversity data, thus demonstrating the utility of direct evidence from Neandertal DNA sequences for understanding recent modern human evolution. Whatever function the two amino acid substitutions might have for human language ability, it was present not only in modern humans but also in late Neandertals. Ongoing in vivo and in vitro experiments should help to delineate these functions.

The news that Neanderthals have the same FOXP2 gene as modern humans, indicating that they may, therefore, have had modern human speech and language, has been misinterpreted in my view. I'd like to make the following points:

1) It is not true that this evidence can be used to draw this conclusion.

2) The FOXP2 gene is not a gene for speech and language.

3) Science reporting has always used framing, this is an example of framing, and this is an example of framing that sucks. This may not mean that all framing sucks, but it does demonstrate how framing can suck.

The role often attributed to the FOXP2 Gene in both the scientific literature and the science press can be summarized in this set of phrases from a recent report in the New York Times:

"Neanderthals, an archaic human species that dominated Europe until the arrival of modern humans some 45,000 years ago, possessed a critical gene known to underlie speech ... a gene called FOXP2 which is associated with language ... The human version of the gene differs at two critical points from the chimpanzee version, suggesting that these two changes have something to do with the fact that people can speak and chimps cannot."NYT:"Neanderthals May Have Had Gene for Speech"

So clearly, it is on the table ... in the nation's premier daily science news print outlet, that FOXP2 is thought (but not with total certainty, of course) to be a speech and language gene. Is it necessary for me to demonstrate that lesser news outlets make this conclusion seem even firmer? No, but it would be fun. The following are phrases from such sources, not attributed here because I don't want to embarrass anybody.

• Modern speech gene found in Neanderthals
• Neanderthals had same version of FOXP2 "language gene" as modern humans
• It's the only gene known so far that plays a key role in language. When mutated, the gene primarily affects language without affecting other abilities.
• Neandertals, humans share key changes to 'language gene'

Let's see, that's one blog, two major news outlets, and the journal Nature. I'll let you guess which source uttered which phrase.

But what is the FOXP2 gene really?

Language is a uniquely human trait likely to have been a prerequisite for the development of human culture. The ability to develop articulate speech relies on capabilities, such as fine control of the larynx and mouth, that are absent in chimpanzees and other great apes. FOXP2 is the first gene relevant to the human ability to develop language. A point mutation in FOXP2 co-segregates with a disorder in a family in which half of the members have severe articulation difficulties accompanied by linguistic and grammatical impairment. This gene is disrupted by translocation in an unrelated individual who has a similar disorder. Thus, two functional copies of FOXP2 seem to be required for acquisition of normal spoken language. We sequenced the complementary DNAs that encode the FOXP2 protein in the chimpanzee, gorilla, orang-utan, rhesus macaque and mouse, and compared them with the human cDNA. We also investigated intraspecific variation of the human FOXP2 gene. Here we show that human FOXP2 contains changes in amino-acid coding and a pattern of nucleotide polymorphism, which strongly suggest that this gene has been the target of selection during recent human evolution. Enard W, Przeworski M, Fisher SE, Lai CS, Wiebe V, Kitano T, Monaco AP, Pääbo S.. (2002). Nature. Aug 22;418(6900):869-72. Epub 2002 Aug 14.

It is arguably true that language is a prerequisite for the phenomenon of "human culture" in the sense of social ontogeny, but not individual ontogeny and not as the chicken as in "chicken before the egg" (or the reverse if you prefer) to human culture as egg. In other words, language does not precede human culture in evolutionary time, but rather, language is part of human culture. The neural differences between a hypothetical pre-cultural human (and that is very hypothetical) and a post-"dawn of culture" human would be those brain differences that we see as distinguishing between the non-cultural (arbitrarily defined as such for the present purposes but obviously a falsehood) chimpanzee-like ape ancestor and, say, you or me.

So when we speak of human intelligence, we may be speaking about the FOX2P gene. Is this the gene that Klein refers to in his somewhat insightful but mostly misguided "one gene theory" ? (Yes, he would likely say, ... or at least "Yea, this really could be the gene.")

OK, that was the first sentence of the FOX2P abstract of Enard et.al. Onward.

We have now switched topics, from language to speech. This happened in the reverse direction in the verbiage cited from the more recent NYT piece on FOXP2 and Neanderthals. One of the great findings of the Language Research Boom of the latter half of the 20th century was this, now pretty much undisputed: Language operates independently of modality. Speech is no more language than getting to work is my car. Now, I quickly add that the authors of the above cited texts do not explicitly tell us that they are conflating speech and language. They are doing it implicitly and tactfully, to avoid the obvious error. But they need to make this leap ... and it is a leap across a fairly narrow but very, very deep chasm ... in order to link the physical (genetic) trait that they have in hand with the grand concept of that one feature that makes us human.

Then, we learn about a broken family. It is not clearly articulated in the paper cited here, but this information came out in later reports as well as under friendly interrogation at conference venues by Terrence Deacon and others: The FOXP2 family -- the grammar-error correlated with a base pair mutation family -- presents a wide range of abnormalities. If FOXP2 caused the consistent grammatical goofiness than it also caused these other attributes.

Many traits work that way. There is a single, widespread phenotype and a smaller number of "mutants" each the expression of a simple mutation that causes some protein to either not be functional at all or to fail in function in a number of contexts. Quite often such individuals are not so dysfunctional that they can't survive, but there is likely overall selection against the variant most of the time. So, each time such a mutation arises, it makes the turn towards that old exit door we call "fixation" and pretty soon everyone in that "deme" is reduced to the more typical and widespread variant.

Sometimes this tells us about a gene that relates to a particular system. Many examples that come to mind have to do with pigment. This is because we humans, as primates, fixate on the visual so we "get" pigment, we see pigmentation. Where I live there are many pockets of all-white squirrels (always in urban areas) and a few pockets of nearly all black squirrels (they can be anywhere) and mostly gray squirrels. If I went out and sampled the squirrels, I could probably put together a pretty good story of pigmentation variation involving a single gene or maybe two for the grey-very dark grey variants (I'm thinking one gene because it does not look like a smooth range to me) and maybe a set of common mutations in any one of a handful of genes that produces the white variety. I would test the hypothesis that the white squirrels have lower individual fitness owing to problems other than pigment loss that arise from this mutant allele, as well as, perhaps, being white all summer (instead of doing what other critters around here do, turning white in winter and back to brownish in summer). And so on.

When I'm done with this research, I'd have a story of metabolic process mainly but not entirely having to do with pigmentation. In fact, I'd have small set of metabolic pathways sharing their "roots" with many other metabolic pathways, but their "branches" largely having to do only with pigmentation. So alleles that "block" the pathway later on cause visible changes in pigmentation, and other secondary changes that also have to do with pigmentation (negative effects on eyesight, increased chance of skin cancer?, being visible to the predators, etc.). Alleles that block the pathway early on also block other pathways, so the direct genetic effects analogous to the simple lack of production of a pigment also occur in other pathways, some of which may be developmental. So you end up not with a white squirrel that may be more likely eaten by a hawk, but rather with a half formed embryo.

The FOXP2 mutation seems to be a non-deadly allele (but we can't be sure of that ... there may be prenatal synergistic effects. What is the rate of miscarriage in FOXP2 women? We don't know) causing a broad-spectrum mutation that has, among many other things, a negative effect on neural development, which is manifest in several ways, one of which happens to be related to linguistic production.

The affected individuals have a range of cognitive problems, but they are all very minor, but one happens to be dyspraxia and thus of great interest. These individuals have difficulty articulating speech and performing certain semi- or fully-automated tasks that are centered in Broca's Area and one or two other spots. FOXP2 in mammals is involved in development of a number of organs, including brains and lungs and esophagus in mice and neural systems related to echolocation in bats. This does not mean it is not involved in lung formation in bats ... that experiment has not been done. In birds, the same gene is involved at least in neural development focusing on the avian cortex, but we don't know about its other functions. The same gene is found in exemplars of most if not all of the vertebrates.

The reason why the gene works this way is because FOXP2 is, you will not be surprised to know, one of the FOX genes, a set of transcription factors. These are genes that turn on during development and ultimately affect the transcription of other genes that are part of that developmental process. An error in a FOX coded transcription factor is likely to have broad effects, most of which will be deleterious.

There are genes that vary a lot (have a lot of alleles) and this makes sense. In some systems, variation is associated with positive fitness (like the MHC genes). Other genes vary very little, and this is generally in the systems where variation is almost always bad. This is probably the case with FOX genes in general, and FOXP2 in particular.

Damage Brains, Damaged Theories

Much of the early understanding of how the human brain works was based on the study of damaged patients. Strokes or trauma would cause an aphasia or other behavioral effect. You study the effect until the patient dies, then you look at the brain to see which part was damaged, and eventually, you get a model of the distribution of functional areas within the brain itself.

Subsequent studies from patients in surgery and MRI's or similar technology indicate that while there is a rough correspondence to the earlier ideas of brain function, things are in fact very different than first expected. There are more areas involved in any given function, with individual areas often having antagonistic subdivisions. So damage to a particular area of the brain, at the gross level, could have very opposite effects each time it happens to a different individual. Naturally, many of the possible kinds of damage that might have revealed something about the function of the brain could not do so because damage to those areas typically resulted in death. For these reasons, the damage-based models were very under determined and very inaccurate.

Think of it this way: Say you knew absolutely nothing about how a car worked inside, but you wanted to find out so you could at least describe how a car works (accurately) and maybe eventually build one from scratch. So you go out and get a bunch of cars You never open the hood, never look at the guts of the car. Instead, you take a shot gun and fire the shotgun at one of the cars and see how it affects performance. Record your results. Fire the shotgun at this car and keep testing the effects, recording them, until the car utterly stops working. If you happen to "kill" the car on the first shot, then you won't get much data from that car.

Now move on the the next car and do the same thing. And so on.

You will eventually get a model of how the car works but it will be pretty coarse, and you will probably have a lot of misconceptions that make your model useless. Especially if you had a mixture of engine-in-front and engine-in-back cars (as would the the case of human brains, studying a mixture of males and females, French-speaking vs. Chinese-speaking, etc. .. as they would have differences in the distribution of linguistic and other functions owing to various hormonal and social effects while growing up).

The linkage between FOXP2 and language is like this. A broken FOXP2 gene is probably almost always fatal early in development. The few alleles that result in a human growing to maturity are going to have strange effects that will not really make much sense. Taking these effects to the next level ... to attributing prior allelic evolution in this particular gene the role of evolutionary foundation for language ... is misleading and inappropriate.

There are probably hundreds of genes like FOXP2 that have to be working a certain way or language function will be impaired. If they are developmental genes, there will be very few alleles. Most alternate alleles will result in inviable embryos or otherwise catastrophic effects that ultimately provide no information to us.

Most or all of these genes probably have a variant in chimpanzees that is also conservative in chimps, but owing to an accumulative 10 to 16 million years of evolutionary time, they will be variant. If you go looking in Neanderthals for these genes, you will almost always find the human variant rather than the chimpanzee variant. This pattern is exactly what we would expect under a basic neutral model, the most likely to apply in this case.

In the broad picture, FOXP2 is very interesting. In the context in which it is usually discussed these days (as the "language gene") it is little more than annoying.

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Krause, Johannes, Carles Lalueza-Fox, Ludovic Orlando, Wolfgang Enard, Richard E. Green, Hernán A. Burbano, Jean-Jacques Hublin, Catherine Hänni, Javier Fortea, Marco de la Rasilla, Jaume Bertranpetit6, Antonio Rosas and Svante Pääbo. (2007) The Derived FOXP2 Variant of Modern Humans Was Shared with Neandertals. Current Biology. doi:10.1016/j.cub.2007.10.008