Anthropology.net

Anthropology.net has gone platinum. With the help of guest bloggers and regular contributors, I have hosted 1,000,000 unique visitors since March of 2007. For a highly specialized niche site with no advertisement campaign I consider this milestone a success.

But, I’m going to bid blogging adieu because I have been accepted to medical school. Once I start, I imagine my studies will be like drinking from a fire hydrant and I won’t have much time to keep up with anthropology news and blogging. This is extremely hard to do, as Anthropology.net has been my baby for the last 4 years. Since the average posts takes several hours to compose, and my primary role as a medical student is to be a study bot, I am going to have to shift focus.

So what does that mean to you guys? Obviously, I won’t be posting, commenting, and moderating. I’m going to miss the discussions I’ve had with the readers and keeping up to date. I still will keep the domain and the site live just in case I ever do decide to return. I do want to extend an invitation to new guest bloggers and contributors, if you wanna pick up anthropology blogging, I’ll be more than happy to host you. Just contact me. Anyways, thank you all for such an awesome ride. I hope to be back once my clerkships start… but that won’t be for at least two more years.

I’m on my way to this symposium, “Humanity’s Genes and the Human Condition,” at UC Berkeley. It should be a day of interesting and relevant talks, especially since the American Society of Human Genetics had their annual meeting this week, and lots of discussions were held about genetic ancestry testing. I’m looking forward to hearing Svante Pääbo and Karin Stromswold talk about human evolution and language, respectively.

If I can live blog, you should check out this post regularly to see minute by minute updates. If I can’t live blog, I will be taking notes the old fashioned way and updating this post later on with my thoughts.

9:04 am: Everyone is getting settled, seems like it’ll be a lively conference. I am live blogging on my phone so excuse the typos.

9:07 am: Joe Palca of NPR is introducing the program. He’s the moderator.

9:10 am: Ed Penhoet is talking about the intersection of genomics and the social sciences. Nobel Prize lecture Sydney Brenner and Gordon Moore (both are in the crowd!) are acknowledged, and the last issue of Science and the genetics of behavior.

9:21 am: David Botstein is taking the stage for the keynote speech. Admits he has no idea what this conference is all about. Everyone laughs.

David Botstein

9:25 am: Botstein is defining many terms like structural & functional genomics. Slide up on size of genomes. Function has little to do with number of genes. Structure and function of protein encoded genes are conserved. He calls it the breadcrumbs of evolution, I like the analogy.

9:32 am: Sequence comparison of DNA is a function of time and the basis of comparing genomes. Tricky inference with associating a gene to a function. The sequence means nothing to function, until it changes the function of the protein. He’s now talking about reviving knockout yeast with inserted human equivalent genes.

9:37 am: Introduced multiple sequence alignments and drawing phylograms. Defining orthologs and paralogs, seems like an intro to genetics 101 class. Talking about duplications in tumorigenesis and using yeasts to see how tumor genes from colon cancer affect yeast phenotyping. Finding mutant genes in humans and using yeast homologs to seek out functional effects.

9:43 am: Variations in sequences, fragment length, one if the first methods to determine how genes vary from one person to another. Distinguishing individuals, DNA hype in pop culture. Using DNA variation in CSI, CODIS: the 13 markets that define the individual.

9:47 am: Single gene diseases like Huntington’s and cystic fibrosis can tell us about basic biological functions of the genes.

9:49 am: Mapping the genome with a microarray chip the has a representative of every gene. Can learn expression of genes in certain tissues at certain developmental stages. Gene expression at certain tissues and stages are conserved between individuals.

David Botstein, Joe Palca, Jasper Rine

9:54 am: Everyone needs a basic understanding of statistics and probabilities. Q&A session with Jasper Rine and Joe Palca.

Jasper Rine took a snipe at ancestry testing, “cheaper assays at determining blue eyes and ear wax.” Haha.

10:37 am: Coffee break is over. Svante Pääbo is taking the stage. Thanking Sydney and confused on howto pitch his talk. Seems like the organizers didn’t prep speakers enough.

Using sequence comparison to understand human evolution. Nothing particularly new being said, but he’s estimating the most common recent ancestor of human-chimp at 4-5 million years ago.

How much variation in human populations exist? 4 base pair differences in 100,000 bases per individual. Shows a tree of gorillas to chimps to bonobos to orangutans and humans.

10:45 am: Are there common variations in populations in Asia, Africa and Europe? There is some geographic-genetic structure to populations. Focus on variants, there are specific variants to each major continent.

Svante Pääbo

10:48 am: Stressing what happened to human lineage after the split from the most common recent ancestor with chimps. Our first problem is defining how humans are unique. We have had a hard time defining human nature: language and tool use in nonhuman primates.

10:50 am: Did human nature evolve recently? We must use Neandertals to find that out but the technical challenge is that Neandertals are thought to be extinct. Replacement vs. Integration of the two species.

10:52 am: High-throughput sequencing let’s us figure out the above questions. Shoutout to 454 technologies, says well have 3 billion base pairs of Neandertal genome by the end of this year. Contamination and degradation of aDNA discussion.

10:55 am: Only .5% contamination has been identified by the last sequencing freeze. Last common ancestor to Neandertals is 800,000 years ago. Neandertals ate deeply diverged. Did mixing occur? Replacement and assimilation again.

10:57 am: Does a random European or African look like a Neandertal genetically? Not right now, but we will have more data. He’s conservative, ‘not by much.’ Loci on chromosome 17, fertility gene western Europe and Eurasia, do modern humans share this sequences? No, but we need to look at more Neandertals.

Dan Rokhsar

11:01 am: He’s sequencing Neandertals not for Neandertals but for a greater understanding of what makes us humans. Now talking about drift and selective swifts, looking for positive selection on modern humans.

Dan Rokhsar, a discussant, is taking the stage. Discussion variation within humans, why did Neandertals die out? Division of labor? Language? Tool making? Agriculture?

11:10 am: Quoting Kremer: more people more brilliant minds, population bottleneck type talk. Humans took advantage of population boom. Question about language, FOXP2, no reason to think Neandertals didnt have language, but talked about recent selective sweep in modern human. Question about what does the 1.2% difference between human & chimp genomes and one about alignments of genomes of modern populations.

11:18 am: Tim White on stage. Talks about religious opposition to human evolution and shows us lots if human fossils. The fossils tell us what they looked like, what they ate, what tools they used. Recommends a synthesis of DNA and fossil evidence.

Tim White

11:21 am: Tim talks about Prabhakar’s paper on finding the unique allele that makes human opposable thumbs. Points out exhibit on human evolution, encourages inspiring youngins.

11:24 am: Question about unique genes to agriculture. Lactose tolerance, audience points out. Amylase and sickle cell. Surprised that Paabo didn’t answer this. An audience member had to answer it! Anyways, culture in these situations led to genetic changes. Question about Flores hominid genomics. Svante says he tried a tooth but did not work. Tim is asked to comment on controversy between paleontology and genetics, about human-chimp split. Paleontologists were wrong in thinking humans-chimps split 15 mya because they interpretted the fossil record incorrectly. Suggests a spring date for Ardipithecus publication that could be most common ancestor. Question about why Neandertals died? Svante says Tim is the paleontologist, Tim bounces back saying Svante is the European!

11:31 am: Moving to talk about infectious diseases. I’m taking a live blogging silence to conserve battery power because after lunch there will be a talk about language. I’ll update this with my old fashioned notes later at home.

Svante Paado & Tim White

1:45 pm: I’m back from lunch. The last talk on immunology was fascinating and I’ll fill in the hand written notes later. Now, Karin Stromswold is gonna talk about language.

1:51 pm: She’s defining language and linguistics and how language touches so many fields like neuroscience, genetics, clinical sciences, pyschology. She’s going to talk about what we know and don’t know about language.

11:54 pm: People do differ in linguistic abilities. Two year old have different know number of words and fluency/proficiency of second languages. What about language impairment, not hearing, so do genetic factors play a role in linguistic variability. She’s drawing an analogy of the genetics if language to the genetics of finger length and number of fingers. Different variants can knock out language while others can effect the extent of language cognition.

Karin Stromswold

1:59 pm: 9+ loci linked to dyslexia and language disorder. She’s talking about the KE family, automsomal disorder. She’s bringing up the new FOXP2-CNTNAP2 paper and how downstream targets of FOXP2 also affect language phenotypes.

2:02 pm: Language disorders do cluster in families despite the fact there’s not a clear Mendelian inheritance. She’s bringing up twin studies to quantify the extent language is genetic. Probability of language impairment between more-or-less identical twins. Compared many variables, between language related and non-language. Vocab is least genetically related, but syntax is.

2:07 pm: Overlap of linguistic and non- linguistic, genetic correlation between fine motor division and linguistic abilities. Why is there a great overlap between syntax and articulation? Perceptive vs. Production. Maybe there’s a hierarchical structure? Not the linear order!

2:11 pm: Key feature of language is that we can embed sentences within each other. Language apes can’t! Argued that us the only specific feature of human communication. We can see non human organism model, but can’t embed multiple messages.

2:13 pm: Genetics affects all aspects of language, and some are specific. Specific neural circuitry, ie articulation and syntax. Different evolutionary histories for faculty. She’s rushing because she’s out if time. Summarizing pleiotropy and phenotype manifests different at different ages. Child can’t speak at two but recovers 100% later, but develops slower.

2:19 pm: Common alleles that contribute to a disease under a environment may not in a different environment. The whole genome + environment = phenotype.

2:20 pm: Dan Geschwind and Marc Feldman take the stage.

Joe Palca, Dan Geschwind and Marc Feldman

Dan’s talking about specificity, genes of language are related to other cognitive traits. He’s talking about CNTNAP2 and where it is expressed and regulated, and assigning function. Asks about recursion, does it have specific heritabilty? Are frontal systems for memory and planning that help us with lanuage? Language us built on existing systems. “We have assymetric brains while chimps don’t,” that’s what Dan says. Karin is explaining how a combination if traits is more complex than keeping things in memory.

2:28 pm: Marc explains the problems of the language if genetics. Herditabilty of height is 90%, know 30 SNPs, but the height of Japanese changed 4 inches in a couple generations. No major genetic changes in the Japanese. Warns that we must be careful with heritability because it doesn’t indicate penetrance. Mentions the New York Times recent coverage on genetics and epigenetic phenomenon.

2:33 pm: Marc says language and genetic trees of populations are very similar, almost too similar. Language and genes are almost synonymous. History of humans is if migrations and who married whom. People marry others who speak their language more often than not, so that’s why languages and genetics correlate.

2:36 pm: “Heritabilities account for the amount of variation,” Karin. Marc says that 30% heritability isn’t good enough. 60% variance due to environment is too random. Audience questions recursion in starlings, which refutes humans being only recursive communicators. Karin, “starlings aren’t technically recursive.” There’s a bit of a pissing match between the two, it gets heated. Joe Palca had to moderate. Molecular biologist asks for definition of recursive.

2:42 pm: Genetics of psychosis up next. I’m gonna stop live blogging again to save battery power. I thought my battery would last longer. I’ll update my hand written notes later.

4:53 pm: Sydney Brenner is about to come up. He’s gonna tell us if this was a successful talk.

Sydney Brenner

4:54 pm: Starts off with a zinger: “Biological evolution for humans has stopped.” Uhh, really Sydney? You better do better than that. He uses an analogy about how if we feel cold, we don’t ‘adapt’ we just kill an animal, skin it, and wear its pelt as evidence of relaxed natural selection. I can see how he’s gonna use cultural evolution as a foundation for the rest of his wrap up, but he didn’t use a good analogy!

4:58 pm: Sydney Brenner coins a new term, social therapeutics. Calls it the new public health. The most outstanding and impacting breakthrough of public health in the last two centuries was advising the public to keep drinking, potable water separate from soiled water. Asks what is the new challenge for public health for the 21st century?

5:00 pm: Obesity! Lists how our hypothalamus drives us to eat more and convert to fat which means our genomes are mal-adapted to the current cultural environment. Jokes that obesity should be a crime. He points out Alta Charo, the previous speaker on Ethics & Epigenetics. Says she must be jailed and forced to cycle to generate electricity. Sydney advocates that this will kill two birds with one stone, obesity and the energy crisis. There are some uncomfortable laughs. The joke isn’t being taken that well.

5:05 pm: Moves on to say that science is extremely flawed nowadays. In his hay day, science was medieval. There was a skilled journeyman and a cohort of apprentices that sought to learn and absorb their mentor’s knowledge. Nowadays big science, big pharmaceuticals and what not, has created drones. Lost is the creative thinking process. The public depends on big science to solve problems, pill for this pill for that, pill for something else. Says, “We must be accountable for our own health.”

5:11 pm: Further advocates to study our fellow humans. How did the human eye evolve? Why not use blind people to see what certain allelic variants cause different phenotypes. We don’t need elaborate mouse models, the world is one big petri dish and the whole human population is one big experiment.

The upcoming issue of Science will be publishing the announcement of a newly discovered 1.2 million-year-old female Homo erectus pelvis. The fossil was found in 2001 at the Gona Study Area in the Afar region Ethiopia. Excavations were completed in 2003.

The 1.2 million year old female Homo erectus pelvis from Gona, Ethiopia

Sileshi Semaw, the leader of the Gona Project, said that the birth canal of this pelvis is 30% larger than earlier estimates based on the 1.5-million-year-old juvenile male pelvis of KNM-WT 15000 (Turkana Boy) found in Kenya. I don’t have an early copy of the paper, but if this is true, this find will make us reevaluate our estimations of Homo erectus growth and development. Current theories, based upon estimations of the existing male skeleton from Kenya, suggested Homo erectus produced babies with only a limited neonatal brain size, and experienced rapid brain growth while still developmentally immature. But as you may know, male and female primate pelvic girdles are extremely different. This new pelvis also tells us of some interesting differences in stature and gait.

Early hominid female pelvic anatomy is basically unknown, in fact we don’t really have much data, really only Lucy’s fragmented pelvis, the 3.2 million year old Australopithecus afarensis. So I’m interested in reading more about this fossil and what it has to tell us of Homo erectus anatomy and early human evolution. I guess I gotta wait until the paper appears in Science. Expect a post about it as soon as I get my hands on the paper.

LB1 (Homo floresiensis)

I watched that NOVA special on Homo floresiensis last night. It was extremely well done. The producers covered a lot of angles, interviewed many key players, presented the information in a clear manner and kept it entertaining. I wish more anthropology related documentaries would use this show as a template.

In lieu of resonating more noise in the echo chamber, I’ll pass you onto John Hawks‘ minute by minute review of the show. But I do want to say the show really effectively addressed some of the critics of the Flores hobbit, including me, by reminding us that evolution is not linear. And even though we’ve seen a linear pattern in previous hominid brain size growth patterns and associated archaeological complexity, it is possible a smaller brained hominid also evolved simultaneously. If I were teaching a paleoanthropology class, I would show this documentary for sure.

For those of you who couldn’t watch it, it is online now in both Quicktime and Windows Media formats. Watch it.

The Pritchard lab has put up an awesome new interface to query the data from the Human Genome Diversity Project, the HDGP Selection Browser. This is browser is phenomenal. You may have known about a previous iteration, Haplotter, also made by the Pritchard lab, which isn’t too user friendly and restricted to only data from four populations.

SLC24A5 SNP (rs2433354) Distribution Frequencies

The new HDGP Selection Browser integrates over 650,000 SNPs from 968 individuals originating from 52 different populations, making it much more granular data. As Razib also stated, the database is queried via GET, meaning we can hotlink to genes of interest, like SLC24A5: a gene related to skin coloration. The authors also provide a map to view how the certain alleles are geographically distributed. For example, see how this SNP, rs2433354 is spread throughout the world. Humans are really genetically different!

Daniel MacArthur, of Genetic Future, has a really awesome do it yourself post on how to use the database. I recommend you check it out if you’re interested in know how to figure out how populations vary on a gene to gene basis. Also, Daniel explains how to look to see if a certain gene or allele has population-specific selection. I won’t rehash and try to steal his thunder since he did such an excellent job.

I tip my hat to the Pritchard lab for developing such a fine database interface. I’ve been working on making my own database and it is not easy to make such a fluid and well executed application and user interface. You guys really made a stellar tool that I will be using a lot in the future.

You may have gotten a heads up from John Hawks that a new documentary on Homo floresiensis is around the bend. It is actually going to air tomorrow and you should catch it. It is titled “Alien From Earth,” premiering tomorrow Tuesday, November 11 at 8pm. I’ll definately be watching.

You’ll be seeing clips from Mike Morwood, Dean Falk, Matt Tocheri, Bill Jungers, and David Lordkipanidze explaining several lines of inquiry in regards to whether or not H. floresiensis unusual features are the result of disease, or the result from the “island effect” that often causes large creatures to evolve to be small, or a previously unrecognized branch of the human family tree.

Homo floresiensis foot compared to a modern human's

Dean Falk will be providing an explanation of her 2007 CAT scan of the H. floresiensis brain and the comparisons she did to microcephalic brains. If you don’t remember, she believes the hobbit represents a healthy, and so far unique, specimen of ancient humanity. But as you may also know, the hobbit’s brain size is really small — around 380 cc and the archaeological assemblage attributed to H. floresiensis is way more advanced than what we’ve seen made by other hominids with similar brain sizes.

Matt Tocheri will be providing an explanation of his 2007 analysis of the wrist bones of the hobbit and comparison to African apes. Tocheri argues that based upon wrist bones, Homo floresiensis is for sure a separate species because the bones are indistinguishable from ancestral African apes or other early hominin-like wrists and resemble nothing like modern humans and Neandertals. Bill Jungers will be arguing that he see similarities of the hobbit’s bones to that of Australopithecus afarensis.

Homo floresiensis mandibles

And since the estimated brain to body mass ratio of H. floresiensis lies between that of Homo erectus and the great apes, David Lordkipanidze discusses the possibility that H. floresiensis could be an unsuspected of our evolutionary tree.

All in all this seems like it should be an excellent synopsis on the latest research. I believe I’ve covered most of it before but video is pretty much more entertaining than reading a blog. Anyways, you can see a teaser clip and find more information about the show on the dedicated NOVA web page. And for those that can’t see the show, an online version will appear sometime afterward. Also of related interest is another documentary on H. floresiensis, which Afarensis live-blogged about several days ago. It is titled “The Hobbit Enigma,” and is also viewable online. I’m gonna try and watch that as well. Afarensis clarfied in the comment belowe that “The Hobbit Engima” and “Alien From Earth” are the same documentary — so why not watch it in advance?

The role of copy number variations (CNVs) has been explained before. In 2006 I discussed the identification of 355 CNVs in the chimpanzee genome, later in 2007 a study fished out human lineage-specific CNVs by comparing them to ones found in chimpanzees, and lastly, this year, another study suggested that CNVs may account for much more genetic variation among individuals than we’ve previously thought. This week the journal Genome Research published a paper which is the largest comparison of CNV differences between human and chimpanzee genomes. The authors specifically sought to identifying regions that have been duplicated or lost during evolution of the two lineages.

Colocalization of CNVs and SDs in the human and chimpanzee genomes

The paper, “Copy number variation and evolution in humans and chimpanzees,” reports on using whole genome tilepath microarrays for the high-throughput identification of these chromosomal deletions and duplications. The arrays had 28,708 DNA clones on them and the DNA from 30 unrelated chimpanzees and 30 unrelated people of African ancestry were used in this comparative genomic screening. Why Africans? Well the  genetic diversity in Africans, especially sub-Saharan populations, is comparable to that of Western chimpanzees. In order compare large scale (kilobase) genetic variation, have populations that both exhibit inherit diversity already knocks out one variable.

DNA was isolated and hybridized to the arrays. Experiments were duplicated. CNVs were validated by FISH and PCR. The authors and reported that each individual had an average of 70 to 80 CNVs. CNVs of genes that genes involved in the inflammatory response and cell proliferation – are more commonly duplicated or deleted and also occur in both species very frequently in orthologous genomic regions, suggesting a tight association to homologous intrachromosomal segmental duplications. Some examples are APOL1, APOL4, CARD18, IL1F7, IL1F8 and are completely deleted from chimp genome. In humans, APOL1 is involved in immune response to the Trypanosoma brucei parasite, transmitted by the tsetse fly, that causes sleeping sickness. IL1F7 and CARD18 play a role in regulating inflammation: therefore, there must be different regulations of these processes in chimpanzees.

Of particular interest is the identification of a CNV: CCL3L1. When compared to chimpanzees, humans have far fewer copies of this gene. Deletions in CCL3L1 have been associated with increased susceptibility to HIV infection. Another gene, TBC1D3, involved in cell proliferation, was reduced in number in chimpanzee compared to human. On average, there were eight copies in humans sampled, but apparently only one in all chimpanzees and this difference. This difference is argued to have been driven by selection.

SNPs are usually the goto comparative genomic marker for most comparative genetic studies. In this situation CNVs were the star. CNVs can have more impactful phenotypic effects than SNPs — where a SNP may alter the shape a final protein makes or alter the promoter sequence, duplications of a gene can lead to more proteins produced. Deletions in copy numbers can also down size the amount of protein produce, affecting the biochemical pathways the product is involved in. So are CNVs more important thant SNPs or other forms of genetic variation? No. They are one of the many structural elements that need to be studied to completely understand the variomes present within human populations and between humans and related species.

G. H. Perry, F. Yang, T. Marques-Bonet, C. Murphy, T. Fitzgerald, A. S. Lee, C. Hyland, A. C. Stone, M. E. Hurles, C. Tyler-Smith, E. E. Eichler, N. P. Carter, C. Lee, R. Redon (2008). Copy number variation and evolution in humans and chimpanzees Genome Research, 18 (11), 1698-1710 DOI: 10.1101/gr.082016.108

One of the pieces to appear in the latest Science is Constance Holden’s synopsis of the core issues discussed at last week’s meeting of the National Human Genome Research Institute: defining geographic populations, handling interpretations of race (especially as as a sociopolitical term), and phrasing results of population genetic studies.

I paid cursory attention to the etymological aspects of the piece. Yes, I know Amerindian isn’t how some Native Americans want to be identified as, and there are some problems with figuring out where European populations end and where Asian populations begin. But I’m hopeful, as more individual genomes are sequenced and released, that genetic patterns can better define populations than cultural and geographic categories have in the past. We don’t necessarily have to rephrase terms or agree on new ones, but can possibly use biological terms, such as allele frequencies, as defining characteristics of populations.

Holden also reviews a discussion on interpretations of fitness — i.e. how some of the public may interpret Carlos Bustamante’s recent Nature paper, where he concluded that European-Americans had more deleterious gene mutations than African-Americans. Does that mean there’s some sort of superiority? No, but that doesn’t mean the public won’t interpret it like that. Should scientists hold back on their reporting their results or sugar coat them just to prevent the public from over analyzing them? I don’t think so.

The must read part of this news piece, especially for anyone news piece for anyone interested in the current state of population genetics and molecular anthropology, is the heated debate between Bruce Lahn and Celeste Condit, a professor of speech communication at the University of Georgia, Athens. Bruce Lahn, as you may know reported 4 years ago that selection in mutations of two genes (ASPM & microcephalin) regulating brain development is more common in Eurasians than in Africans. Condit argued that Lahn’s results have a political message embedded, a common mistake that many uneducated critics of population genetics repeat. We’ve had similiar misconceptions raised on Anthropology.net. Lahn retored back that some…

“are almost like creationists” in their unwillingness to acknowledge that the brain is not exempt from selection pressures.”

Oh snap! The whole meeting didn’t seem to be fruitless though, most agreed that suppressing freedom of reporting results as they are observed in the name of political correctness is not conduicive to the scientific method.

C. Holden (2008). PERSONAL GENOMICS: The Touchy Subject of ‘Race’ Science, 322 (5903), 839-839 DOI: 10.1126/science.322.5903.839a

Tomorrow’s issue of Science hosts lots of interesting papers, one of which is titled, “A Test of Climate, Sun, and Culture Relationships from an 1810-Year Chinese Cave Record,” and reports on the analysis of a 1.2-meter-long stalagmite from Wanxiang Cave in northern China. The analysis tells us that the rock holds records of waning Asian monsoon rains around 1,100 years ago. The dry spell was due to weakening of the sun, possibly from a sunspot, and this climate change is thought to have been what brought down the Tang dynasty.

Map of Wanxiang Cave, China

Stalagmites are calcium carbonate mounds which form from dripping groundwater. Chemical analysis of this Wanxiang stalagmite told the researchers that there’s a lot of uranium and exceptionally low clay-borne thorium. That allowed them to do a uranium-thorium radiometric dating of the layered deposits down to an interval of 2.5 years. With such accuracy, the authors were able to calculate precise dates for variations in the stalagmite’s oxygen isotope composition. Oxygen isotope levels reflect variations in rainfall near the cave. The isotope levels match that of drought conditions.

Comparing this result to Chinese historical records of rainfall, the authors matched the chemical analysis to the written record. Furthermore, previously published climate record from a lake on the southern coast of China also confirm this. This 9th-century dry period is also thought to be what also doomed the Mayan civilization. Poor rainfall affected crops and the carrying capacity of each civilization.

P. Zhang, H. Cheng, R. L. Edwards, F. Chen, Y. Wang, X. Yang, J. Liu, M. Tan, X. Wang, J. Liu, C. An, Z. Dai, J. Zhou, D. Zhang, J. Jia, L. Jin, K. R. Johnson (2008). A Test of Climate, Sun, and Culture Relationships from an 1810-Year Chinese Cave Record Science, 322 (5903), 940-942 DOI: 10.1126/science.1163965

Today’s issue of Nature has a brief essay on the role of language in cultural evolution. The authors touch up on a lot basics, such as anatomical localization of brain activity related to language and tool making, FOXP2, and how language has helped humans pass on cultural information more effectively than any other form of communication. Overall, it is a well written review that I want to pass on.

Related, Erin from the Spitton, shared news of the identification of a new language related SNP on the gene CNTNAP2. The paper which reports this is titled, “A Functional Genetic Link between Distinct Developmental Language Disorders,” and was published in the New England Journal of Medicine. I believe it is open access, I got to the full text with no problem. The authors hypothesized that neural pathways downstream of FOXP2 can also affect language impairment.

To identify possible downstream candidates that might be involved in typical SLI, the authors transfected a human brain cancer cell line (SH-SY5Y) to continually express FOXP2. FOXP2 is a transcription factor, meaning it is a controller of the expression of other genes. If it is mutated, it can’t regulate its targets properly and leads to different, sometimes mutant, phenotype. The used a type of test called the chromatin immunoprecipitation (ChIP) assay which identifies how and often where proteins, like the FOXP2 transcription factor, bind to specific regions of the genome. This is done by using specific antibodies that recognize a specific protein or a specific modification of a protein, in this situation anti-FOXP2 antibodies.

The ChIP assay showed that the FOXP2 transcription factor binds to a particular, novel region of interest, the first intron of gene CNTNAP2. When transcribed and translated, CNTNAP2 normally encodes for the protein CASPR2 — a protein that is localized and understood to function in the nodes of Ranvier on myelinated neurons. Of further interest, CNTNAP2 is expressed in the human cerebral cortex, specifically the orbital gyrus and superior frontal anlage, spanning the inferior and middle frontal gyri — all regions know to related to language cognition.

To make sure that FOXP2 was for sure targeting this region, and wasn’t mislead due to any conformational changes that came from the antibody it was complexed with, the authors did some PCR and sequencing and saw that this region of interest, intron 1, does have matching known consensus, binding sequence for FOXP2. They did some other tests that shows that this sequence is highly specific to FOXP2… all of which suggests that this site on CNTNAP2 is definitively a binding site for FOXP2 (CAAATT).

The authors next varied the amount of FOXP2 expression and tried to see if it affects the ultimate expression of CNTNAP2. They were able to show there is a correlation — CNTNAP2 transcript levels were lowest where there are higher levels of FOXP2, suggesting that FOXP2 down regulates CNTNAP2. We haven’t know about FOXP2-CNTNAP2 interactions before, because FOXP2-bound fragment of CNTNAP2 is outside of the classically defined regulatory regions that promoter based microarrays identify… So identifying this pathway is very commendable.

With this downstream candidate gene isolated the authors moved to see how polymorphisms in CNTNAP2 manifest language phenotypes. Their population sample was made up from children from 184 different families where at least one child had a specific language impairment (SLI). The children had wildtype FOXP2, but children who carried the guanine nucleotide at rs17236239 SNP on CNTNAP2 had worse scores on a test that measures their ability to reproduce nonsense words like “brufid” and “contramponist.”

Now don’t get me wrong, this SNP, rs17236239, ain’t on intron 1 — where FOXP2 binds. FOXP2 was used as bait to fish out what gene bites to it. When CNTNAP2 was figured out to be a new novel target of FOXP2, the authors tried to see if CNTNAP2 variations also affect language. And they do. What’s also of interest is that other SNPs in the same regaion that rs17236239 is found also have CNTNAP2 as been linked to delayed speech in children with autism.

I’m really impressed with this paper. It’s a gem. Well written and straight forward. I don’t regularly read papers of such caliber, to be honest… So I really appreciate when I do. The new language related gene is also very important as we begin to piece together the complex network of genes and proteins, anatomy and behaviors that have allowed us to have language and use it.

Eörs Szathmáry, Szabolcs Számadó (2008). Being Human: Language: a social history of words Nature, 456 (7218), 40-41 DOI: 10.1038/456040a

S. C. Vernes, D. F. Newbury, B. S. Abrahams, L. Winchester, J. Nicod, M. Groszer, M. Alarcon, P. L. Oliver, K. E. Davies, D. H. Geschwind, A. P. Monaco, S. E. Fisher (2008). A Functional Genetic Link between Distinct Developmental Language Disorders New England Journal of Medicine DOI: 10.1056/NEJMoa0802828