Anthropology.net

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

If you’re a regular reader of Dienekes blog, you’d know he’s consistently raised concerns that calibrations of molecular clocks don’t quite fit the bill. Yesterday, he posted an addendum and shared a new paper in which authors advocate that molecular clock can be calibrated upon an archaeological context (not phylogeny-based) and human mtDNA estimates of dates of population and phylogenetic events should be adjusted to time-dependent mutation rate estimates.

I’m not gonna get into a rehashing of Dienekes’ post, I wouldn’t do as good of a job even if I did… but you should jump on over and read what he has to say and how he explains his criticisms of how the clock has been calibrated in the past. I want to spend some time in this post discussing some of the results of the paper he shared, “Characterizing the Time-Dependency of Human Mitochondrial DNA Mutation Rate Estimates,” in Molecular Biology and Evolution. The authors sought to establish genealogy-based estimates of the mtDNA mutation rate using both hypervariable and coding region data, they also wanted to figure out if multiple hits  affect the discrepancy between the different methods of mutation rate estimation.

So they setup new genealogy-based rates from 2,500 to 50,000 years ago using mtDNA from populations in the Canary Islands, Polynesia, Micronesia, North America, Taiwan, Indonesia, and Oceania. The populations were selected based upon relative isolation and the  available archaeological dates for the time of first human arrival, haplotypic data from neighboring regions, and indigenous haplotypes for that region.

The authors were able to calculate that the evolutionary mutation rate between approximately 2,500 and 50,000 years ago was much different than that from 50,000 to 6 million years ago. They suggest that since earlier mutation rates, ones based upon pedigrees, are not affected by the processes of
bottlenecks and selection, except for purifying selection on lethal alleles, they can’t weed out the effects demographic processes. Using their time-dependent approach they observe that molecular clock was accelerated for large Neolithic populations and is similar to the pedigree rate, but for the smaller Paleolithic hunter-gatherers it was much lower…. makes sense, as populations grow, variability accelerates.

B. M. Henn, C. R. Gignoux, M. W. Feldman, J. L. Mountain (2008). Characterizing the Time-Dependency of Human Mitochondrial DNA Mutation Rate Estimates Molecular Biology and Evolution DOI: 10.1093/molbev/msn244

A new paper in the open access journal PLoS Genetics reports on a comparison of genetic, geographic, and linguistic patterns of the diverse populations found on the major islands of the Bismarck Archipelago and Bougainville, Melanesia. The paper is titled, “Genetic and Linguistic Coevolution in Northern Island Melanesia.” I think that Simon Greenhill of HENRY may know a bit more about these populations, languages and region than I, but I’m gonna still try and summarize the paper and briefly discuss the results.

The earliest inhabitants of the area arrived around 40,000 years ago, but there was an additional migration into the region about 3,300 years ago. We know that primarily because of the linguistic diversity. The two major languages are Oceanic and Papuan. Oceanic, being a major branch of the widespread Austronesian language family, and the Paupuan languages, likely descendants of languages spoken by people who began arriving in the region more than 40,000 years ago. The rugged geography of the region has been a cause for a lot of the diversification. Despite their regional affinities, the two languages do not form a very coherent language family.

Genetic, Geographic & Linguistic Distances Of Melanesian Popultions

The study sampled 776 individuals from 33 linguistically based populations, which averages to about 23 individuals per population. Each individual was typed on 751 different autosomal microsatellites. The languages were compared on 108 different structural linguistic features. The authors applied two different tests to figure out if genetic and linguistic similarities were formed following early population splits and isolations or if the genetic and linguistic similarities were formed through continuing genetic and linguistic exchange between neighboring populations.

The authors were able to figure out that genes moved freely than languages between nearby populations, regardless of the language family (compare Figures B to D). Language exchanges, on the other hand, have been particularly limited between neighboring Oceanic and Papuan languages (check out Figure D & F). In certain regions, like the rugged interior of the largest island, New Britain, the authors found strong correlations between genetic, linguistic, and geographic distances when compared to their less restricted coastal neighboring populations. They are almost always distinctly different. While extremely restricted to several islands, this study shows us a scenario where language barriers do not particularly hinder genetic exchange, but geography still does.

Keith Hunley, Michael Dunn, Eva Lindström, Ger Reesink, Angela Terrill, Meghan E. Healy, George Koki, Françoise R. Friedlaender, Jonathan S. Friedlaender (2008). Genetic and Linguistic Coevolution in Northern Island Melanesia PLoS Genetics, 4 (10) DOI: 10.1371/journal.pgen.1000239

Last month I was excited to share some research about the chemical composition of Ötzi, the 5,000 year old Tyrolean Iceman that has captured my attention for quite sometime. Today, I’m even more excited to share that the complete mitochondrial genome of Ötzi has been sequenced using a combination of PCR amplification and 454 sequencing. The research has been published in Current Biology. You can find it under the title, “Complete Mitochondrial Genome Sequence of the Tyrolean Iceman.”

I’ve covered the details behind Ötzi before. I’ll give you a quick run down in case you forgot or never knew about him. Ötzi is the name given to mummy discovered on September 19^th, 1991, around 3,270m above sea level, in the Eastern Alps near the Austro-Italian border. His remains were dated to be , 5,350–5,100 years old, and was remarkably preserved because of the cold climate. We have an idea what his last meal was and what he wore. He’s thought to have been around 46 years old, his fertility has been questioned, and his cause of death seems to have been rather horrific — severely wounded by an arrow and some blunt force trauma to his face.

Previous researchers have sequenced some of his mitochondrial genome, specifically the hypervariable segment (HVS-I). Two nucleotide transitions, at positions 16224 and 16311, indicate that Ötzi’s mtDNA belonged to haplogroup K, a subclade of the major west Eurasian haplogroup U. The authors of the new Current Biology paper decided to completely sequence the mitochondrial genome of Ötzi using 454 pyrosequencing technology. They’ve compared the sequence to 115 published complete mtDNA sequences from modern individuals, and constructed a phylogeny of the K haplogroup.

The sequencing run seems to have been rather uneventful. I’ve covered 454 technology before, but to recap it is sequencing by synthesis, which involves template DNA being immobilized, and solutions of each nucleotide added. They hybridize to their complement at the first unpaired base of the template. The hybridization reaction lets off light, because the polymerase enzyme is paired with another other chemiluminescent enzyme. A high resolution photo is taken and any remaining unbound nucleotide is removed and then another wash of another base is made. With the array approach developed by 454, it is possible to generate over 100 million nucleotide data in a 7 hour run with a single machine.

The authors reported they made 45,829 reads, but only 42,695 reads, or 93.2% of the total, were usable. Several gaps in the mitochondrial genome were observed, so PCR products were cloned into vectors and sequenced with conventional Sanger technology. When compared with the revised Cambridge Reference Sequence (rCRS), the consensus sequence showed 30 mtDNA transitions. A phylogenetic comparison was made to all 115 haplogroup K complete sequences currently available. The authors confirm that Iceman’s sequence falls within haplogroup K.

But, transitions at positions 3513 and 8137 on the Iceman’s mitochondrial genome indicate that his maternal lineage belongs a K1 subhaplogroup but not to any of the three subclades into which K1 is currently further subdivided (K1a, K1b, and K1c). The authors conclude that the Iceman’s mtDNA, belong to a novel branch of K1, not yet identified before. They’re calling it K1ö.

I’m not gonna get into much of a discussion about contamination because the samples were taken from thawed tissue from the mummy’s rectum. Many lines of evidence show that there was a lot of endogenous mtDNA that woulda muddled out any contaminating DNA and the results reconfirm the previous HVS-1 results. Anyways, this is the oldest complete H. sapiens mtDNA genome generated to date. The results show that as the frequency of genetic lineages change over time, due to genetic drift, some variants die out. Based upon the mtDNA, it is highly unlikely that Ötzi has any modern day maternal relatives… unless we sequence more than 115 haplogroup K carriers.

Luca Ermini, Cristina Olivieri, Ermanno Rizzi, Giorgio Corti, Raoul Bonnal, Pedro Soares, Stefania Luciani, Isolina Marota, Gianluca De Bellis, Martin B. Richards, Franco Rollo (2008). “Complete Mitochondrial Genome Sequence of the Tyrolean Iceman” Current Biology, DOI: 10.1016/j.cub.2008.09.028

Nature Genetics just published a brief correspondence on the evolution of promoter regions in the human genome. The basis of this study relies on the observation that 46% of promoter regions in the human genome have a higher number of nucleotide substitutions than corresponding introns. The authors don’t make the distinction that positive selection, relaxed constraint or mutation rate are the causes of this observation, but they suggest that they have been important to hominid evolution and the genetic diversity of humans.

If you don’t know what a promoter is, I’ll give you a quick run down. Promoters are regions of the genome that are upstream from genes. Regulatory elements such as transcription factors bind to these regions and either start the expression of the gene that is downstream or regulate expression. Any changes to these region can affect phenotypes related to the gene downstream. Between two populations with the exact same intronic sequence of a gene, a difference in the promoter region can have dramatic effects.

In this current paper, “Rapidly evolving human promoter regions,” the authors respond to a previous paper on the subject. They reanalyzed the alignments used by the previous paper. They asked whether each promoter region as a whole is evolving more rapidly than local intronic sequences. They find that almost all (569/575; 99%) of the promoter regions identified by the previous paper as containing positively selected sites have a higher average substitution rate than their paired intronic regions.

The previous authors say that positive selection is at play. They based this conclusion on positive selection on introns. But the current authors caution that promoters are unusual genomic regions, and cannot be compared to selection on introns. They simiply conclude that promoters have higher neutral substitution rates. The previous authors respond to this in this same issue of Nature Genetics. They defend that the current authors methodology “do[es] not affirm their contention that mutation is generally accelerated in primate promoters.” Either way, both teams have identified that promoter regions of the human genome are highly diversified. The reason why they are, is still unresolved, but these conclusions do fall in line with previous ones that I’ve covered here on Anthropology.net:

• Differences of gene expression between human populations
• Identifying Cis-Acting Elements that regulate Human Gene Expression
• Gene Regulation, the driving force in Human Evolution
• Understanding Adaptive Evolution in the Human Genome

Martin S Taylor, Tim Massingham, Yoshihide Hayashizaki, Piero Carninci, Nick Goldman, Colin A M Semple (2008). Rapidly evolving human promoter regions Nature Genetics, 40 (11), 1262-1263 DOI: 10.1038/ng1108-1262

Ralph Haygood, Olivier Fedrigo, Gregory A Wray (2008). Reply to “Rapidly evolving human promoter regions” Nature Genetics, 40 (11), 1263-1264 DOI: 10.1038/ng1108-1263

If you look at the time stamp of both Bora‘s and Greg Laden‘s posts, you’d notice that they just broke the embargo on a new study of a prehistoric case of tuberculosis that was supposed to go live at 5pm PST, 8pm EST. Now that the news is out, albeit slightly earlier than expected, I figure I should also cover it. The press release touts that the human remains from a site called Atlit-Yam in Israel have provided genetic evidence for the earliest known cases of tuberculosis, dated at 9,000 years old.

Atlit-Yam, Israel

Atlit-Yam is a site currently submerged 8 to 12 meters below sea level in the North Bay of Atlit. The site is about 10 kilometers south of Haifa. Previous researchers have radiocarbon dated the site to be 9,250 to 8,160 years old. The site has yielded both floral and faunal remains along with tools. The floral remains and the faunal remains indicate that these people already made the transition from hunter gatherer subsistence to a fully Neolithic lifestyle.

Human remains were also recovered from the site, and some show characteristic bone lesions that are signs of tuberculosis, specifically the remains of a 25 year old woman buried with an infant. The age of the woman was estimated based on dental attrition, epiphyseal ring ankylosis and the symphysis of the pubis, which are all pretty solid markers. The bones were preserved in a muddy dark clay substance, an anaerobic condition which is very conducive for DNA preservation. Even though other elements have tuberculosis caused lesions, the researchers specifically analyzed the ribs and arm bones of the female adult and long bones of the infant.

Paleopathological lesions on Neolithic infant bones.

Because of the excellent conditions for DNA preservation, the authors moved ahead with two molecular techniques to determine if tuberculosis was the causative agent of the lesions. First they deployed a PCR experiment, specifically designing a primer set to the fish out Mycobacterium tuberculosis sequences. Secondly, they utilized a reverse phase high performance liquid chromatography (HPLC) method that tried to isolate mycobacterial cell wall mycolic acids from the sample.

The PCR yielded positive results with the multi-copy IS6110 & IS1081 fragments, obtained from the rib of the woman and infant long bone. The fragments were confirmed to be valid by sequencing. These fragments are restriction fragment length polymorphisms and are commonly used as definitive signatures of Mycobacterium tuberculosis. The authors compared their PCR fragment sequences to Genbank and also reported that the sequences are identical to those in the NCBI database for M. tuberculosis.

The HPLC also provided evidence that there are mycobacterial cell wall molecules present in the samples. The woman had the highest amount per mg of bone, at 20.14 pg, while the infant had a smaller amount at 0.12 pg/mg. Nonetheless, both lines of evidence along with the visual lesions show that at least two of the people of Atlit-Yam had a tuberculosis problem.

As I mentioned, it seems that the press is going to love the ‘earliest evidence of TB’ sound bit. But it’s not particularly true because, John Kappelman announced the discovery of tuberculosis in a 500,000 year old Homo erectus cranial fragment last yet. I have my doubts about the H. erectus diagnosis though. The authors also did review other paleo-tuberculosis cases such as the 17,000 year old bison and the 4,000 year old Egyptian human bone and soft tissue sample. Either way, this is the earliest report of the disease in humans that has been confirmed by molecular means.

One last thing, Atlit-Yam is among the very few Pre-Pottery Neolithic sites where domesticated cattle have been found. Tuberculosis in humans was thought to have a zoonotic origin, perhaps transmitted to humans from domesticated cattle during the Neolithic revolution. But that theory has been on the rocks, and these individuals were clearly infected with Mycobacterium tuberculosis, not Mycobacterium bovi, which infects cattle. Could the cattle have caused the tuberculosis in these two individuals? What do you think?

Israel Hershkovitz, Helen D. Donoghue, David E. Minnikin, Gurdyal S. Besra, Oona Y-C. Lee, Angela M. Gernaey, Ehud Galili, Vered Eshed, Charles L. Greenblatt, Eshetu Lemma, Gila Kahila Bar-Gal, Mark Spigelman, Niyaz Ahmed (2008). Detection and Molecular Characterization of 9000-Year-Old Mycobacterium tuberculosis from a Neolithic Settlement in the Eastern Mediterranean PLoS ONE, 3 (10) DOI: 10.1371/journal.pone.0003426

When the headlines behind this story came across my RSS reader the other day, I was gonna file it under my proverbial “Captain Obvious” category. The basic premise is the potential link between last name and Y chromosome type. We already know that in deep ancestries, like among Jewish people, the Cohen Modal Haplotype (CMH) is notably frequent amongst Cohens. Cohens are a lineage of Jews believed to be direct relatives to the Biblical Aaron. They have a relatively strict marital tradition, one where the last name is preserved paternally.

Many other cultures are structured paternally and last names are inherited, for the most part, from the father’s family. Turi King made this otherwise obvious observation and tried to look for similar Y-chromosome haplotypes among two and half thousand men with 500 different last names. She presented her results to the Doctoral Inaugural Lectures being held in the Frank and Katherine May Lecture Theatre, Henry Wellcome Building, University of Leicester last week.

While not as deep as Cohens, there should be a linkage with almost any man’s last name and his Y-chromosome genetics… So long as name changes, adoptions and multiple foundations of the same last name by different individuals (like Smith) haven’t been prevalent. And that’s why I changed my mind about posting this research. King explains,

“The last name Smith is a good example of this as it derives from the occupation of blacksmith so many men could have taken on the last name Smith. This means that instead of just one type of Y chromosome being associated with a last name, many different types of Y chromosomes would be associated with this single last name. On the other hand, for rarer names, there may have been just one founder for the name and potentially all men who bear that last name today would be descended from him and could be connected into one large family tree.”

When King compared the Y-chromosome makeup of non-related individuals limited down to 40 last names, she was able to see that last names like Attenborough and Swindlehurst showed that over 70% of the men shared the same or near identical Y chromosome types whereas last names such as Revis, Wadsworth and Jefferson show more than one group of men sharing common ancestry but unrelated to other groups.

Ultimately, King was able to show between two men that share the same last name, there is a 24% chance of sharing a common ancestor through that name but that this increases to nearly 50% when their last name is rare. For forensic scientists out there, especially forensic anthropologists who regularly deal with skeletal remains, this can be a godsend because a prediction of a male’s last name is potentially possible from DNA alone. Now disclaimer aside, the press release didn’t really mention her methodology, i.e. how many loci she compared. Of course, the more the merrier. Either way, I’m sure many out there will look forward to larger comparisons of last-name to Y-chromosome correlations.

Earlier this year, I wrote a massive summary on the genetics of pigmentation for one of my graduate courses. I wasn’t particularly keen on the topic before but it has since grown on me and I’m now a big fan. So to read from Yann, Dienekes, and Razib that one of the key pigmentation genes, SLC45A2 is involved in hair color among Polish people, I was both excited and, well, frankly not very surprised.

Before I drag you into a review of the paper let me first introduce the gene and its function. SLC45A2 stands for solute carrier family 45, member 2. It is found on the short arm of chromosome 5. Not very informational, but the protein it ultimately encodes for is known as membrane-associated transporter protein (MATP). As the name implies, this protein is thought to regulate traffic melanosomal proteins into melanosomes, organelles within pigmentation cells (melanocytes) where melanin is produced. Melanin functions as a protective agent. It is dark in color and accumulates in cells in reaction to sunlight, absorbing light and protecting the nuclear genome from mutations caused by the ionizing radiation from UV rays. Thus, making MATP and the genetics of SLC45A2 an important part of the skin pigmentation pathway.

Recent studies have shown that certain variants of MATP affect pigmentation, such as Cook et al., 2008 and Graf et al., 2007. In the latest piece that everyone is buzzing about, “Association of the SLC45A2 gene with physiological human hair colour variation,” the authors were able to make an significant association between one of two non-synonymous polymorphisms in SLC45A2 and the hair color phenotype of a Polish population.

Inspired by Razib's example: Marzena Cieslik, Miss Poland 2006

The two SNPs are rs26722 and rs16891982. Both are missense mutations that encode for a different amino acids. The first SNP, rs26722, is a change from a guanine base to an adenine at position 907 of the mRNA transcript. This swap to an adenine affects the resultant the codon, creating a lysine on position 272 of the amino acid sequence instead of a glutamic acid residue (annotated as E373K). Similarly, rs16891982, is also a switch of a guanine but for a cytosine base on a different position of the transcript, 1214. The leucine residue on position 374 is thus changed to a phenylalanine (annotated as L374F).

Biochemistry aside, these two end products, MATP-E272K and MATP-L374F, have distinct population frequency distributions, especially MATP-L374F. Among the Polish sample of 392 individuals of varying skin, hair, and eye color, the rare allele is L374… Found in only 2.3% of the population. The MATP-374F allele is represented in 97.7% of the Polish sample. Curiously, all people who carried the rare allele had dark hair. The authors calculated the odds the L374 genotype increased the likelihood a person would have dark hair by 7 times.

Razib linked up an awesome resource, called ALFRED, the allele frequency database which shows the distribution of rs16891982 world wide. You can see that in northern Europe, 374F is the prevalent allele. Only when you get to Italy, Spain, Turkey, do you begin to see more of the L374 allele (the dark hair allele).

Worldwide Distribution of the rs16891982 SLC45A2 Allele

This all makes sense, people who carry a cytosine on position 1214 of the SLC45A2 mRNA have lighter color hair than those who carry a guanine (L374). A similar distribution frequency was observed a German and Japanese sample by Nakayama et al., 2002 & Yuasa et al., 2004 & Yuasa et al., 2006. 96.5% of Germans had the lighter 374F allele. 100% of Japanese had the darker L374.

But why?

I returned to one of the previous studies I mentioned earlier, the Cook et al. paper, “Analysis of Cultured Human Melanocytes Based on Polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P Loci.” The authors of this paper grew primary melanocytic cells with specific mutations and tried to see the effects they had on melanin content and tyrosinase activity. In their array, one of their comparisons included the impacts of the MATP-L374 variant to the MATP-374F variant. They found that MATP-L374 cells expressed significantly lower MATP transcript levels compared to MATP-374F ones.

I’ve spent a lot of time thinking about this and quite frankly, I’m very confused. Correct me if I’m wrong, but lower levels of MATP transcript means less transport proteins translated and available to bring melanosomal proteins into the cells. Less building blocks equals less melanin. And less melanin should equal lighter pigmentation. So why do people who have dark hair have the less productive allele?

Come to think of it, there could be many different reasons, actually. Biochemical pathways are hardly ever a 1:1 mechanism. There’s lots of redundancy and sometimes one component isn’t the point man. For example, other parts of the pathway, such as tyrosinase, an enzyme that catalyzes the production of melanin, is higher in darker skin. Other transport proteins, such as SLC24A5/NCKX5 are also part of the melanin and melanosome production network and could have a different impact.

Either way, there are a few curious things to come out of all of this… We now know a definitive allele that affects hair color. Albeit, how is still up in the air, ’cause darker haired people come with less membrane-associated transporter proteins on their melanocytes. But still, there is a distinct structure to the distributions of these haplotypes.

Wojciech Branicki, Urszula Brudnik, Jolanta Draus-Barini, Tomasz Kupiec, Anna Wojas-Pelc (2008). Association of the SLC45A2 gene with physiological human hair colour variation Journal of Human Genetics DOI: 10.1007/s10038-008-0338-3

The other day Dienekes pointed out a paper on ancestral human population dynamics within Africa before the out of Africa migrations. The paper is very similar to one I reviewed in April, which also focuses on the diversity of the mitochondrial haplogroup L — one of the oldest mtDNA haplogroups out there.

The new paper, “Bayesian coalescent inference of major human mitochondrial DNA haplogroup expansions in Africa,” published in the Proceedings of the Royal Society B, uses coalescent theory to investigate past population sizes of each of the four major African mtDNA haplogroups (L0-L3). 224 different mitochondrial genomes were analyzed and the comparison yielded some similar results to the previous paper I mentioned. But remember, the last paper investigated the time of the emergence of each haplogroup. This paper focuses on effective population sizes.

Anyways, for starters, the results show that three distinct demographic histories can be seen from the underlying the four haplogroups. Two of the oldest haplogroups, L0 and L1, show exponential growth from 213,000 to 156,000 years ago. The previous paper suggested that the L0 and L1 split about 200,000 years ago. Soon after this split, one of the the paleoafrican branches L0 established what we now consider sub-Saharan Khoisan peoples.

L1 split up into the L2 and L3 branches sometime around 127,000 to 72,000 years ago, again consistent with the previous paper. The L2 and L3 branches show two exponential growth periods, one around 86,000 to 61,000 years ago and another around 20,000 to 12,000 years ago. The authors observed a distinct expansion of the L3 branch around 12,000 to 8,000 years ago. They suggest that,

“L3 did not simply spill over into Eurasia, but was driven as part of an expansion that had begun in sub-Saharan Africa thousands of years earlier.”

While this date is a bit later than the one suggested in the previous paper, both indicate that there were deep African migrations within Africa. The later expansions of L2 and L3, coincide with environmental and cultural changes, such as the greening of the Sahara and emergence of pastoralism. The authors write that,

“The timing of the L3 expansion-8-12kyr prior to the emergence of the first non-African mtDNA lineages-together with high L3 diversity in eastern Africa, strongly supports the proposal that the human exodus from Africa and subsequent colonization of the globe was prefaced by a major expansion within Africa, perhaps driven by some form of cultural innovation.”

Quentin D. Atkinson, Russell D. Gray, Alexei J. Drummond (2008). Bayesian coalescent inference of major human mitochondrial DNA haplogroup expansions in Africa Proceedings of the Royal Society B: Biological Sciences, -1 (-1), -1–1 DOI: 10.1098/rspb.2008.0785

As you know, we have many symbiotic relationships with bacteria. In fact, the average human gut contains about 1 kilogram (2.2 pounds) of these microscopic cells, some of which are beneficial. If you’ve ever had to take antibiotics, you may have come to learn how dependent we are on certain strains of bacteria to process plant materials… albeit through a rather uncomfortable experience. Certain flora, like E. coli, live in our intestines and help us synthesize vitamins K and B-complex, which are then absorbed by the body.

But microbes provide us with more than just dietary aide. Actually, microbes offer a unique line of evidence into investigating human migrations, which is crucial to have in anthropology. Since they evolve faster due to their exponentially expedited life span, we can trace how human population diverged from one another. One of my favorite papers on the subject was last year’s support for the Out of Africa model of human migrations using the genetics of Helicobacter pylori, another gut dwelling bacterial species.

Helicobacter pylori

A similar study on the topic was published today in the open access journal PLoS One. The title, “Amerindian Helicobacter pylori Strains Go Extinct, as European Strains Expand Their Host Range,” does a great job at explaining the main results of the paper. But I’ll try to provide a bit more detail in this post.

First, let me introduce the microbe to you. Unlike some of the other flora that reside inside of us, H. pylori, is more or less a parasite and a nasty one at that — known to cause stomach and intestinal cancers because of the chronic inflammation it causes. The inflammation stems off of the reaction of a component of its gram-negative staining walls, a lipopolysaccharide that initiates an immune response. However, most of us play host to this species and do a good job at keeping it under control. Inflammation only becomes a problem when combined with other deficiencies in the health and immune system of the individual.

The authors of this study made 131 bacterial cultures, 19 of which came from from Africans, 36 from Spanish, 11 from Koreans, 43 from Amerindians and 22 from South American Mestizos. They lysed the cells from the cultures and did lots of PCR and sequencing reactions for 7 housekeeping genes from each of the 131 cultures. When they did a comparison of the sequences they noted an interesting, but consistent result: decreased diversity of H. pylori strains in the human group with the least genomic diversity.

In other words, Native American human populations, who experienced a population bottleneck while crossing Beringia, also inadvertently caused a H. pylori bottleneck! We’ve suspected that Native American populations have undergone a bottleneck because looking at their ABO blood group diversity, they show a remarkable dominance of O blood type — something not seen in European and African populations.

Among Mestizo people, H. pylori genetic diversity was high. That’s cause Mestizos are people of mixed ancestry — a hodgepodge of Spanish and Native American hybrids. In fact, the authors could see the hybridization in the H. pylori from these people. Although bacteria reproduce asexually, they have this phenomenon, called recombination, which is effectively a sharing of parts of DNA. Mestizo H. pylori had some signatures from Amerindian H. pylori and some from European H. pylori indicating their was a sharing of H. pylori genes from these two different populations, just as there was a sharing of human genes.

Even though I’ve made this point before, similar to languages, material culture, and our own genetics, the genetics of organisms associated with humans, be it bacteria, rats, etc. can effectively tell us a lot about human migrations. This paper documents how a founder effect of sorts, a decrease of genetic variation of H. pylori among Native Americans due the effects of crossing Beringia some 15,000 years ago. It also documents the increase in genetic diversity of H. pylori as these Native American groups mixed with European ones.

Maria G. Domínguez-Bello, Maria E. Pérez, Maria C. Bortolini, Francisco M. Salzano, Luis R. Pericchi, Orlisbeth Zambrano-Guzmán, Bodo Linz, Angus Buckling (2008). Amerindian Helicobacter pylori Strains Go Extinct, as European Strains Expand Their Host Range PLoS ONE, 3 (10) DOI: 10.1371/journal.pone.0003307