The oldest known plague

New ancient DNA research has identified the bacterium Yersinia pestis, which causes the deadly and epidemic illness known as plague, in Chalcolithic and Bronze Age Central Eurasia, from Altai to Poland and the Caucasus.

S. Rasmussen, M.E. Alentoft et al., Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago. Cell 2015. Open access → LINK [doi:http://dx.doi.org/10.1016/j.cell.2015.10.009]

Summary

The bacteria Yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. How and when it originated remains contentious. Here, we report the oldest direct evidence of Yersinia pestis identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago. By sequencing the genomes, we find that these ancient plague strains are basal to all known Yersinia pestis. We find the origins of the Yersinia pestis lineage to be at least two times older than previous estimates. We also identify a temporal sequence of genetic changes that lead to increased virulence and the emergence of the bubonic plague. Our results show that plague infection was endemic in the human populations of Eurasia at least 3,000 years before any historical recordings of pandemics.

The bacterium was yet unable to cause the bubonic form of the plague and could not spread by means of fleas either. Instead it probably caused pneumonic and spticemic plague and was propagated by coughing and sneezing, much like the flu. 

Figure 1

Archaeological Sites of Bronze Age Yersinia pestis
(A) Map of Eurasia indicating the position, radiocarbon dated ages and associated cultures of the samples in which Y. pestis were identified. Dates are given as 95% confidence interval calendar BC years. IA: Iron Age.
(B) Burial four from Bulanovo site. Picture by Mikhail V. Khalyapin. See also Table S1.

In spite of the hype, the prevalence of the plague was low: only 7 out of 101 samples tested positive for the bacterium, ranging from c. 2800 BCE (Altai) to c. 1000 BCE (Southern Azerbaijan, Iran). A 7% prevalence is still significant but it's also obvious that 93% of the people in the period studied did not die from the plague, so let's not exaggerate, alright?

The exaggeration is already seeded in the study with passages as this one:

These early plagues may have been responsible for the suggested population declines in the late 4^th millennium BC and the early 3^rd millennium BC (Hinz et al., 2012, Shennan et al., 2013).

Neither of the referenced studies (see here and here) deals with Eastern Europe, West Asia or Central Asia, and the analyzed dates only slightly overlap with the period in which Y. pestis is found, so I fail to see the logic. It is true that there could be a coincidence in the case of Little Poland, where both Y. pestis and a demographic decline are apparent c. 2000 BCE but in all other cases it really needs a good deal of imagination to make any association.

In any case, it is clear that even the most virulent plague ever known, the Black Death, only managed to make a dent in the European demography and its consequences were not those of demographic re-expansion of the less affected populations (Polish, Basques) but a double socio-economic transition in two phases:

1. The lack of manpower in the decades after the Black Death allowed the lower classes to renegotiate their situation in various ways. It was the period in which the feudal system was most dramatically eroded, with peasants gaining control on their farmed lands and lords losing large shares of their exploitative profits, while being forced to compete against each other for whom offered best working conditions to the now scarce farmers, who, legally or not, migrated from the worst places to the ones offering better conditions. 
2. A reaction by profit-jealous landlords that largely replaced farming by husbandry, which requires less manpower. A well known case were the English enclosures, which would, slowly but steadily, set the foundations of Capitalism.

This is explained by historian, actor and director Terry Jones in the following video:

So the consequences and context of these epidemics must be considered adequately and not distorted nor simplified unduly in the line of the infamous Guns, Germs and Steel book, which greatly exaggerates the consequences of natural epidemics and is one of the favorite books of Eurocentric reactionaries with a distorted and overly simplistic view of things. One of the "virtues" of the epidemic hype is that it somehow absolves the winners from their historical crimes, blaming them on nature almost alone: instead of genocide, they use these deformations of reality to blame the mass destruction of whole nations and populations, be them Neanderthals or Native Americans, on "natural causes". 

Hypocrisy!

Instead I wonder about the real demographic impact, not yet well assessed, of the epidemics, and also about the real socio-economic consequences of such demographic declines. Of course, they could have allowed for localized migrations in the aftermath of the epidemics (or whatever other causes of demographic declines) but they should also have favored at least short-term renegotiations of the social order in favor of the suddenly scarce working classes (farmers). This "upward mobility" and partial "leveling" of what was already in many cases a feudal-like caste society should have dramatic effects in the constitution of the nations of the Bronze Age, regardless of later re-adjustments and expansions, which one can imagine as an imperfectly cyclical process.

Breastfeeding improves IQ and other mental developments in children depending on duration

Again nurture (environment) seems to be much more important than nature (genetics) in what regards to human intelligence.

A new study show that not just the mere fact of breastfeeding but the duration of natural motherly nutrition (and maybe the emotional elements attached to it) is strongly correlated with IQ (but not memory and learning).

Mandy B. Belfort et al., Infant Feeding and Childhood Cognition at Ages 3 and 7 YearsEffects of Breastfeeding Duration and Exclusivity. JAMA Pediatrics 2013. Pay per view → LINK [doi:10.1001/jamapediatrics.2013.455]

Abstract

Importance  Breastfeeding may benefit child cognitive development, but few studies have quantified breastfeeding duration or exclusivity, nor has any study to date examined the role of maternal diet during lactation on child cognition.

Objectives  To examine relationships of breastfeeding duration and exclusivity with child cognition at ages 3 and 7 years and to evaluate the extent to which maternal fish intake during lactation modifies associations of infant feeding with later cognition.

Design, Setting, and Participants  Prospective cohort study (Project Viva), a US prebirth cohort that enrolled mothers from April 22, 1999, to July 31, 2002, and followed up children to age 7 years, including 1312 Project Viva mothers and children.

Main Exposure  Duration of any breastfeeding to age 12 months.

Main Outcomes and Measures  Child receptive language assessed with the Peabody Picture Vocabulary Test at age 3 years, Wide Range Assessment of Visual Motor Abilities at ages 3 and 7 years, and Kaufman Brief Intelligence Test and Wide Range Assessment of Memory and Learning at age 7 years.

Results  Adjusting for sociodemographics, maternal intelligence, and home environment in linear regression, longer breastfeeding duration was associated with higher Peabody Picture Vocabulary Test score at age 3 years (0.21; 95% CI, 0.03-0.38 points per month breastfed) and with higher intelligence on the Kaufman Brief Intelligence Test at age 7 years (0.35; 0.16-0.53 verbal points per month breastfed; and 0.29; 0.05-0.54 nonverbal points per month breastfed). Breastfeeding duration was not associated with Wide Range Assessment of Memory and Learning scores. Beneficial effects of breastfeeding on the Wide Range Assessment of Visual Motor Abilities at age 3 years seemed greater for women who consumed 2 or more servings of fish per week (0.24; 0.00-0.47 points per month breastfed) compared with less than 2 servings of fish per week (−0.01; −0.22 to 0.20 points per month breastfed) (P = .16 for interaction).

Conclusions and Relevance  Our results support a causal relationship of breastfeeding duration with receptive language and verbal and nonverbal intelligence later in life.

Related is also:

Dimitri A. Kristakis, Breastfeeding and CognitionCan IQ Tip the Scale? JAMA Pediatrics 2013. Pay per view → LINK [doi:10.1001/jamapediatrics.2013.470]

Extract

In the developed world, where the benefits of breastfeeding are not measured in terms of life or death or even serious morbidity, the question has been what benefits might motivate mothers to both initiate and sustain it consistent with the World Health Organization and American Academy of Pediatrics recommendations.^1- 2 The reduction of gastroenteritis, otitis media, and atopic eczema in the first year of life is supported by a strong evidence base.³ While these are important and desirable outcomes, none in and of themselves have dramatic public health consequences, particularly beyond early childhood. On the other hand, the connection between breastfeeding and cognition has lifelong and widespread implications. Whether a causal linkage between the two exists has long been debated, in part, because most existing studies are observational and have failed to adjust for maternal IQ. Given the known association between educational attainment or intelligence and breastfeeding, failure to adjust for maternal IQ may confound any observed effects on infants.

The study by Belfort et al⁴ in this month’s issue of JAMA Pediatrics, although observational, has many notable strengths including controlling for maternal intelligence, as well as features of the home environment that promote cognitive function. Assuming these findings are in fact robust, what are the public health implications?

A synthesis of the findings is also available at Science Daily. They explain that the association with motherly fish intake mentioned in the first abstract is not statistically significant. They also quote the authors as saying:

In summary, our results support a causal relationship of breastfeeding in infancy with receptive language at age 3 and with verbal and nonverbal IQ at school age. These findings support national and international recommendations to promote exclusive breastfeeding through age 6 months and continuation of breastfeeding through at least age 1 year.

Christakis in turn emphasizes that while the absolute distinction between breastfeeding and bottle feeding is important (in the USA only 70% of  White mothers and only 50% of Black ones initiate breastfeeding at all), a major problem is the lack of persistence of this natural form of nutrition, caused mostly by social and labor pressures, including the absurd stigma against breastfeeding in public, not so long a common sight. Only 35% of European-American and a mere 20% of African-American mothers still breastfeed by their baby's age of six months. He says:

Breastfeeding in public should be destigmatized. Clever social media campaigns and high-quality public service announcements might help with that. As with lead, some of these actions may require legislative action either at the federal or state level. Let's allow our children's cognitive function be the force that tilts the scale, and let's get on with it.

See also: 

• Breatsfeeding vastly improves brain development in early infancy
• Not more than 2% of educational attainment can be attributed to genes
• Emotional care or neglect of young children decisive for brain size, intelligence
• Epigenetics and IQ variability
• Intelligence genes more elusive than Higgins' boson
• Breastfeeding greatly increases IQ

Exercise causes epigenetic changes in fat cells

It seems more and more obvious than rather just burning fat, what exercise does against overweight is to alter the way the body works in more subtle pathways.

Tina Röhn et al., A Six Months Exercise Intervention Influences the Genome-wide DNA Methylation Pattern in Human Adipose Tissue. PLoS Genetics 2013. Open access → LINK [doi:10.1371/journal.pgen.1003572]

Abstract

Epigenetic mechanisms are implicated in gene regulation and the development of different diseases. The epigenome differs between cell types and has until now only been characterized for a few human tissues. Environmental factors potentially alter the epigenome. Here we describe the genome-wide pattern of DNA methylation in human adipose tissue from 23 healthy men, with a previous low level of physical activity, before and after a six months exercise intervention. We also investigate the differences in adipose tissue DNA methylation between 31 individuals with or without a family history of type 2 diabetes. DNA methylation was analyzed using Infinium HumanMethylation450 BeadChip, an array containing 485,577 probes covering 99% RefSeq genes. Global DNA methylation changed and 17,975 individual CpG sites in 7,663 unique genes showed altered levels of DNA methylation after the exercise intervention (q<0.05). Differential mRNA expression was present in 1/3 of gene regions with altered DNA methylation, including RALBP1, HDAC4 and NCOR2 (q<0.05). Using a luciferase assay, we could show that increased DNA methylation in vitro of the RALBP1 promoter suppressed the transcriptional activity (p = 0.03). Moreover, 18 obesity and 21 type 2 diabetes candidate genes had CpG sites with differences in adipose tissue DNA methylation in response to exercise (q<0.05), including TCF7L2 (6 CpG sites) and KCNQ1 (10 CpG sites). A simultaneous change in mRNA expression was seen for 6 of those genes. To understand if genes that exhibit differential DNA methylation and mRNA expression in human adipose tissue in vivo affect adipocyte metabolism, we silenced Hdac4 and Ncor2 respectively in 3T3-L1 adipocytes, which resulted in increased lipogenesis both in the basal and insulin stimulated state. In conclusion, exercise induces genome-wide changes in DNA methylation in human adipose tissue, potentially affecting adipocyte metabolism.

Figure 2. Analysis flowchart.

Table 3. Changes in adipose tissue DNA methylation in response to a 6 months exercise intervention. Significant CpG sites (q<0.05) with the biggest change in DNA methylation (>8%).

Breatsfeeding vastly improves brain development in early infancy

Nature vs nurture? Where genetics often fail to explain most differences in cognitive development in a satisfactory manner, environmental causes instead show outstanding importance. 

A very clear case is breastfeeding, which not only provides the best nutrition for babies but also key emotional support. And new research only emphasizes this.

From Science Daily:

The research found that by age 2, babies who had been breastfed exclusively for at least three months had enhanced development in key parts of the brain compared to children who were fed formula exclusively or who were fed a combination of formula and breastmilk. The extra growth was most pronounced in parts of the brain associated with language, emotional function, and cognition, the research showed.

(...)

The study showed that the exclusively breastfed group had the fastest growth in myelinated white matter of the three groups, with the increase in white matter volume becoming substantial by age 2. The group fed both breastmilk and formula had more growth than the exclusively formula-fed group, but less than the breastmilk-only group.

"We're finding the difference [in white matter growth] is on the order of 20 to 30 percent, comparing the breastfed and the non-breastfed kids," said [lead researcher Sean] Deoni. "I think it's astounding that you could have that much difference so early."

Ref. (pay per view): Sean C.L. Deoni, Douglas C. Dean, Irene Piryatinksy, Jonathan O'Muircheartaigh, Nicole Waskiewicz, Katie Lehman, Michelle Han, Holly Dirks. Breastfeeding and early white matter development: A cross-sectional study. NeuroImage, 2013; DOI: 10.1016/j.neuroimage.2013.05.090

Bisphenol A severely disrupts fetal epigenetics

Water bottle containing bisphenol A

The most controversial chemical compound bisphenol A is found in many plastics, including sometimes those used as food or water containers. This study adds to the long list of known harms of this chemical, which nevertheless remains widely allowed.

Martha Susiarjo et al., Bisphenol A Exposure Disrupts Genomic Imprinting in the Mouse. PLoS Genetics 2013. Open access → LINK [doi:10.1371/journal.pgen.1003401]

Abstract

Exposure to endocrine disruptors is associated with developmental defects. One compound of concern, to which humans are widely exposed, is bisphenol A (BPA). In model organisms, BPA exposure is linked to metabolic disorders, infertility, cancer, and behavior anomalies. Recently, BPA exposure has been linked to DNA methylation changes, indicating that epigenetic mechanisms may be relevant. We investigated effects of exposure on genomic imprinting in the mouse as imprinted genes are regulated by differential DNA methylation and aberrant imprinting disrupts fetal, placental, and postnatal development. Through allele-specific and quantitative real-time PCR analysis, we demonstrated that maternal BPA exposure during late stages of oocyte development and early stages of embryonic development significantly disrupted imprinted gene expression in embryonic day (E) 9.5 and 12.5 embryos and placentas. The affected genes included Snrpn, Ube3a, Igf2, Kcnq1ot1, Cdkn1c, and Ascl2; mutations and aberrant regulation of these genes are associated with imprinting disorders in humans. Furthermore, the majority of affected genes were expressed abnormally in the placenta. DNA methylation studies showed that BPA exposure significantly altered the methylation levels of differentially methylated regions (DMRs) including the Snrpn imprinting control region (ICR) and Igf2 DMR1. Moreover, exposure significantly reduced genome-wide methylation levels in the placenta, but not the embryo. Histological and immunohistochemical examinations revealed that these epigenetic defects were associated with abnormal placental development. In contrast to this early exposure paradigm, exposure outside of the epigenetic reprogramming window did not cause significant imprinting perturbations. Our data suggest that early exposure to common environmental compounds has the potential to disrupt fetal and postnatal health through epigenetic changes in the embryo and abnormal development of the placenta.

Rare early North Chinese skull suggests inbreeding depression

Again very quickly on a matter that seems to be of some interest:

Xiu-Jie Wu, Song Xing & Erik Trinkaus, An Enlarged Parietal Foramen in the Late Archaic Xujiayao 11 Neurocranium from Northern China, and Rare Anomalies among Pleistocene Homo. PLoS ONE, 2013. Open access → LINK [doi:10.1371/journal.pone.0059587]

Abstract

We report here a neurocranial abnormality previously undescribed in Pleistocene human fossils, an enlarged parietal foramen (EPF) in the early Late Pleistocene Xujiayao 11 parietal bones from the Xujiayao (Houjiayao) site, northern China. Xujiayao 11 is a pair of partial posteromedial parietal bones from an adult. It exhibits thick cranial vault bones, arachnoid granulations, a deviated posterior sagittal suture, and a unilateral (right) parietal lacuna with a posteriorly-directed and enlarged endocranial vascular sulcus. Differential diagnosis indicates that the perforation is a congenital defect, an enlarged parietal foramen, commonly associated with cerebral venous and cranial vault anomalies. It was not lethal given the individual’s age-at-death, but it may have been associated with secondary neurological deficiencies. The fossil constitutes the oldest evidence in human evolution of this very rare condition (a single enlarged parietal foramen). In combination with developmental and degenerative abnormalities in other Pleistocene human remains, it suggests demographic and survival patterns among Pleistocene Homo that led to an elevated frequency of conditions unknown or rare among recent humans.

The authors argue, according to previous research that Xujiayao remains are neither Homo erectus nor early Homo sapiens but it's difficult to say, as the Chinese Academy tends to be ambiguous on these matters and so is Trinkaus.

The most recent datings (OSL) for the site suggest MIS 4 ages (60±8 and 69±8 ka BP). However earlier datings (U-Th series) claimed a much older age: 104-125 Ka BP (MIS 5). The later dates would certainly fit with my expectations for the arrival of H. sapiens to the area.

Whatever the case, the authors conclude that this EPF anomaly is in line with a long list of Paleolithic cases of developmental anomalies that they suspect caused by inbreeding within the parameters of small hunter-gatherer populations. 

To the extent that these abnormalities can be considered congenital or cannot be securely diagnosed, these considerations raise questions regarding the population dynamics of Pleistocene humans. To what extent could this pattern reflect small, highly inbred populations, which were also demographically unstable, resulting in both the increased appearance of congenital deleterious conditions and in their subsequent disappearance through local population extinction? Demographic instability appears to have been characteristic of most Pleistocene human populations [78]–[80]. It remains unclear, and probably untestable, to what extent these populations were inbred, but close genetic relationships have been suggested for one Neandertal sample [81] and some Upper Paleolithic burial groups [76], [82], [83].

Another SE Asian genetic adaption to Malaria

Malaria has been one of the greatest challenges to human survival in the tropics and subtropical areas, which make up the bulk of our early distribution as species. In response we have developed a number of genetic-biological strategies of which the best known is the allele that causes the sickle cell disease in homozygotes but protects heterozygotes against the deadly infection in a clear example of balancing selection. This is not however the only adaption against malaria.

A new study explores a SE Asian (including Southern Chinese) adaption that also seems to be a way to fight against the disease, which is a variant of Alpha-Thalassemia:

Qin-Wei Qiu et al., Evidence of recent natural selection on the Southeast Asian deletion (--SEA) causing alpha-thalassemia in South China. BMC Evolutionary Biology 2013. Open access → LINK [doi:10.1186/1471-2148-13-63]

Abstract (provisional)

Background

The Southeast Asian deletion (--SEA) is the most commonly observed mutation among diverse alpha-thalassemia alleles in Southeast Asia and South China. It is generally argued that mutation --SEA, like other variants causing hemoglobin disorders, is associated with protection against malaria that is endemic in these regions. However, little evidence has been provided to support this claim.

Results

We first examined the genetic imprint of recent positive selection on the --SEA allele and flanking sequences in the human alpha-globin cluster, covering a genomic region spanning ~410 kb, by genotyping 28 SNPs in a Chinese population consisting of 76 --SEA heterozygotes and 138 normal individuals. The pattern of linkage disequilibrium (LD) and the long-range haplotype test revealed a signature of positive selection. The network of inferred haplotypes suggested a single origin of the --SEA allele.

Conclusions

Thus, our data support the hypothesis that the --SEA allele has been subjected to recent balancing selection, triggered by malaria.

See also:

• Malaria and sickle cell anemia do not correlate well in Asia
• The other red cell disease that protects against the other malaria
• IL-4 genetic combo protects Indian hunter-gatherers from Malaria

Mouth bacteria changed with civilization... for worse

A premise of Primitivism, which is not really a doctrine or philosophy but more like realistic approach to the human condition, is that our evolutionary past is shaped almost totally by hunter-gathering. That we are basically hunter-gatherers in a jump or maybe formal suit. Why? Because some 95% of the biological history of Homo sapiens, as a formed species is one of hunter-gathering, not of productive economy nor civilization. This percentage can be extended to maybe 99.5% if we consider the whole history of the genus homo, etc. And that is a lot. 

Do I digress? Well, maybe not so much after all. The evolutionary news today is in any case that the bacterial ecosystems in our mouths have been degenerating since Neolithic, and then again with Industrialization. As Not exactly rocket science (a National Geographic blog written by Ed Yong) explains the bacteria in our mouth is not all hostile but, at least for hunter-gatherers, often balanced: some bacteria may attack our teeth but then others protect and even repair them. Much like the better known bacteria of our guts, there is a general balance in which, naturally at least, symbiosis with the human needs tends to dominate. After all those bacteria live in our mouths and therefore need it to exist in good shape: they may not be exactly "aware" of their own needs or the benefits of harm they bring to us but evolution fixes it in the long run, of course. 

Epipaleolithic foragers from Poland with a rather thick plaque, plaque that retained in millennial hibernation the bacteria of their mouth, have provided evidence of Prehistoric hunter-gatherers having a healthy, balanced mouth bacterial ecology. 

Instead Medieval English, who were already eating many carbohydrates from cereals, illustrate with their plaque the beginning of mouth bacterial decadence. There are a total of 34 studied remains between these two dates, illustrating that this change happened exactly with the Neolithic Revolution.

The members of the modern research team used their own mouths as reference for the modern bacterial environment. The results were rather depressing: industrialization has created many refined, unbalanced, foods (white cereals and sugar especially) that cause our mouths to be the boon of dentists.

We are what we eat
(source)

A similar kind of bacterial ecology decadence was observed in a previous study between the guts of Burkinabe farmers' children and those of Italian urban ones. The latter have ecosystems dominated by well-fed firmicutes, associated to obesity.

Reference paper:  Christina J. Adler et al., Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the Neolithic and Industrial revolutions. Nature 2013. Pay per view → LINK [doi:10.1038/ng.2536]

IL-4 genetic combo protects Indian hunter-gatherers from Malaria

Or, more precisely, protects many of those who have it in diverse populations but it is most concentrated among hunter-gatherers of the so-called Ancestral Tribal Populations (ATP).

Aditya Nath Jha et al., IL-4 Haplotype -590T, -34T and Intron-3 VNTR R2 Is Associated with Reduced Malaria Risk among Ancestral Indian Tribal Populations. PLoS ONE 2012. Open access ··> LINK [doi:10.1371/journal.pone.0048136]

Abstract

Background

Interleukin 4 (IL-4) is an anti-inflammatory cytokine, which regulates balance between TH1 and TH2 immune response, immunoglobulin class switching and humoral immunity. Polymorphisms in this gene have been reported to affect the risk of infectious and autoimmune diseases.

Methods

We have analyzed three regulatory IL-4 polymorphisms; -590C>T, -34C>T and 70 bp intron-3 VNTR, in 4216 individuals; including: (1) 430 ethnically matched case-control groups (173 severe malaria, 101 mild malaria and 156 asymptomatic); (2) 3452 individuals from 76 linguistically and geographically distinct endogamous populations of India, and (3) 334 individuals with different ancestry from outside India (84 Brazilian, 104 Syrian, and 146 Vietnamese).

Results

The -590T, -34T and intron-3 VNTR R2 alleles were found to be associated with reduced malaria risk (P<0.001 for -590C>T and -34C>T, and P = 0.003 for VNTR). These three alleles were in strong LD (r²>0.75) and the TTR2 (-590T, -34T and intron-3 VNTR R2) haplotype appeared to be a susceptibility factor for malaria (P = 0.009, OR = 0.552, 95% CI = 0.356 –0.854). Allele and genotype frequencies differ significantly between caste, nomadic, tribe and ancestral tribal populations (ATP). The distribution of protective haplotype TTR2 was found to be significant (χ²₃ = 182.95, p-value <0.001), which is highest in ATP (40.5%); intermediate in tribes (33%); and lowest in caste (17.8%) and nomadic (21.6%).

Conclusions

Our study suggests that the IL-4 polymorphisms regulate host susceptibility to malaria and disease progression. TTR2 haplotype, which gives protection against malaria, is high among ATPs. Since they inhabited in isolation and mainly practice hunter-gatherer lifestyles and exposed to various parasites, IL-4 TTR2 haplotype might be under positive selection.

The protection is not absolute but it holds very strong statistical significance for the R2-R3 heterozygous combo, as shown in fig. 1:

Figure 1. Distribution of IL-4 intron-3 VNTR polymorphism.

A and B: genotype and allelic distribution between malaria case control groups, respectively; C and D: genotype and allelic distribution among caste, nomadic, tribe and ancestral tribe, respectively.

Combo that is most common (near-optimal distribution) among the ATPs. The correlation holds for the four linguistic families with variations being more a matter of individual ATP tribes: from 35% among the AoNaga (TB, Nagaland) to 67% among the Baiga (IE, Madhya Pradesh) or 63% among the Onge (Jarawa-Onge, Andaman Is.)

 

See also:

• The other red cell disease that protects against the other malaria
• Malaria and sickle cell anemia do not correlate well in Asia

Folic acid deficiency detected in Olduway c. 1.5 Ma ago

The headlines and even contents in commercial media and blogs alike are all about meat eating (much of which must be blamed on the lead researcher himself, who seems to have a bias) but it does not need to be the reason at all and rather reflects an ideological bias. 

All that paleoanthroplogists have detected is a folate deficiency in a fragment of a skull of what is probably an Homo erectus/ergaster young child (est. 2 y.o. or less) from East Africa. There is no dietary isotope research that can confirm or deny the meat hypothesis.

Manuel Domínguez-Rodrigo et al., Earliest Porotic Hyperostosis on a 1.5-Million-Year-Old Hominin, Olduvai Gorge, Tanzania. PLoS ONE 2012. Open access ··> LINK [doi:10.1371/journal.pone.0046414]

The authors found exactly this:

Figure 3. Ectocranial (top right) and endocranial (top left) close-up views of the OH 81 fossil, accompanied by magnifications of the porotic hyperostosis paleopathology as observed ectocranially (lower left) and edge-on at the diploic-table junction (lower right).

Scale = 1 mm.

They conclude that this porosity of the bone, known as porotic hyperostosis, should indicate folate deficiency (in which vitamins B9 and B12 are involved) caused by malnutrition. They also argue that weaning may have been a cause because, at least in other contexts, it is a key period for nutritional illnesses, often implying B12 deficiency. 

The archaeo-environmental context (persistent drought) may have contributed to this illness and death as well.

Still the emphasis in meat eating, even if possibly correct, strikes me as very ideological:

The presence of anemia-induced porotic hypertostosis on the 1.5 Ma OH 81 hominin parietal, indicates indirectly that by at least the early Pleistocene meat had become so essential to proper hominin functioning that its paucity or lack led to deleterious pathological conditions. 

Were do we get that from, Dr. Domínguez? Some sort of nutritional lack seems obvious but there are many reasons why folate deficiency can develop; for example excess of solar radiation (it has been proposed that the ancestral dark skin of humans serves to prevent folate loss, rather than cancer, which only develops in the long term). Was this child an albino maybe? 

Or had it celiac disease (another possible cause of malabsorption)?

And (update), as the Subersive Archaeologist discusses rather emotionally, the maybe simplest explanation: that malaria could be the cause is dismissed in the paper without satisfactory explanation.

Sure thing that lack of sufficient animal protein intake is a plausible cause but by no means demonstrated. An isotopic analysis could support or reject this hypothesis, although I am uncertain if it is possible to perform on this particular bone.


See also labels Paleolithic food, human evolution and pigmentation in this blog.


Update (Oct 10): I just got to know that there is a formal criticism by two anthropologists, J.J. Crandall and D.L. Martin, roughly in the same line as mentioned here. Read it here.

Update (Oct 16): Domínguez at al.  replied to the previous criticism here. However their only argument against a malaria-caused PH is:

PH still occurs in much lower frequencies on skeletons in this earlier transitional period than is observed in more recent skeletal populations from the sedentary, agrarian Neolithic.

... what fails to be conclusive.

The Maasai: rich ancestry, lactase persistance and low cholesterol

Maasai warriors jumping (cc by javic)

There is a new paper at the Public Library of Science on the genetics of the Maasai with emphasis in diet-related aspects:

Kshitij Wagh et al., Lactase Persistence and Lipid Pathway Selection in the Maasai. PLoS ONE, 2012. Open access ··> LINK [doi:10.1371/journal.pone.0044751]

Abstract

The Maasai are a pastoral people in Kenya and Tanzania, whose traditional diet of milk, blood and meat is rich in lactose, fat and cholesterol. In spite of this, they have low levels of blood cholesterol, and seldom suffer from gallstones or cardiac diseases. Field studies in the 1970s suggested that the Maasai have a genetic adaptation for cholesterol homeostasis. Analysis of HapMap 3 data using Fixation Index (Fst) and two metrics of haplotype diversity: the integrated Haplotype Score (iHS) and the Cross Population Extended Haplotype Homozygosity (XP-EHH), identified genomic regions and single nucleotide polymorphisms (SNPs) as strong candidates for recent selection for lactase persistence and cholesterol regulation in 143–156 founder individuals from the Maasai population in Kinyawa, Kenya (MKK). The non-synonmous SNP with the highest genome-wide Fst was the TC polymorphism at rs2241883 in Fatty Acid Binding Protein 1(FABP1), known to reduce low density lipoprotein and tri-glyceride levels in Europeans. The strongest signal identified by all three metrics was a 1.7 Mb region on Chr2q21. This region contains the genes LCT (Lactase) and MCM6 (Minichromosome Maintenance Complex Component) involved in lactase persistence, and the gene Rab3GAP1 (Rab3 GTPase-activating Protein Catalytic Subunit), which contains polymorphisms associated with total cholesterol levels in a genome-wide association study of >100,000 individuals of European ancestry. Sanger sequencing of DNA from six MKK samples showed that the GC-14010 polymorphism in the MCM6 gene, known to be associated with lactase persistence in Africans, is segregating in MKK at high frequency (~58%). The Cytochrome P450 Family 3 Subfamily A (CYP3A) cluster of genes, involved in cholesterol metabolism, was identified by Fst and iHS as candidate loci under selection. Overall, our study identified several specific genomic regions under selection in the Maasai which contain polymorphisms in genes associated with lactase persistence and cholesterol regulation.

The study actually has two elements of interest for my point of view, on one side it is the dietary aspects of Maasai genetics underlined in the title and the abstract but then there is a more generic element of understanding the relevant population genetics with the help of STRUCTURE,  reflected in fig. 1 but better addressed in the supplemental materials (Appendix S1).

The Maasai as product of 6 ancestral populations

K=6 is what STRUCTURE indicates as clear best fit (lowest log probability of fit) in a no-admixture model and all the six reconstructed ancestral populations are all present in them (unlike what happens for example with the CEU sample of European ancestry):

From Appendix S1 - click to expand
CEU: European-Americans (USA), ASW: African-Americans (USA)
LWK: Luhya (Kenya), MKK: Maasai (Kenya), YRI: Yoruba (Nigeria)

We can see that the influence of West Eurasian genetics (teal) appears to be almost nil in Africa, although the Maasai (MKK) have some (c. 2%), probably infiltrated via Ethiopia, Somalia or Sudan.

West African genetics (pink) are slightly more influential in the Maasai but only c. 10%.

Instead the Maasai display four different East African specific "ancestral populations" of which two are larger and the other two smaller in the sampled populations:

• The yellow component is almost exclusive of the Maasai (69%), with some very minor penetration in other populations.
• The green component is more outstanding among the Luhya (32%), reaching barely 5% among the Maasai.
• The brown component is again almost exclusive of the Maasai (12%), with some individuals apparently displaying it as very dominant.
• Finally, the purple one is almost exclusive of the Maasai but at much lower frequecies (3%). However it is also dominant in a few individuals.

The fact that the Maasai show obviously marked individual variance at levels not apparent in other populations, and that this variance includes some smaller "mystery" components, seems to mean that they are in ongoing or very recent admixture with other populations (maybe other Maasai clans of distinctive origin, maybe other pre-Bantu East African peoples). It indicates that there is still a lot to research in the Population genetics of East Africa, what requires of extensive new sampling among the many diverse small ethnicities of the Upper Nile and nearby regions.

Yes to milk, no to cholesterol

The other, more central aspect of this study is the localization of specific genomic regions or even alleles that guarantee that this pastoralist people can largely live off the milk produced by their cows and, quite interestingly, not to have circulatory problems because of the associated excess cholesterol.

The authors detected the following regions as very clearly under selection (several approaches being convergent in their detection):

Fig. 5

The first of these regions, in chromosome 2, seems particularly long and selected for both lactase persistence (the ability to digest lactose as adult) and low cholesterol, according to this paper. 

The region in chromosome 7 regulates the enzyme Cytochrome P450, related to oxidation processes in metabolism of lipids, steroids, drugs and toxins, probably also regulating cholesterol.

See also in this blog:

• Claim that cholesterol related gene was positively selected in Africa but not elsewhere
• Positive selection for arthritis and short-size alleles in Eurasia?
• Khoesan genetics helping to understand the evolutionary history of Humankind as a whole
• Khoesan autosomal genetics
• North African autosomal genetics (also considering the Maasai). 
• Chad basin mtDNA
• Sudanese autosomal genetics
• African diversity and the possible origins of Humankind
• Eastern Pygmies are not mtDNA L1

I also recommedn Ethio Helix blog, generally quite informative in all things African and genetic.

Claim that cholesterol related gene was positively selected in Africa but not elsewhere

This is one of those genetic studies whose claims are so strongly counter-intuitive that I do not know what part to believe the less. However the raw data is clearly there and that is interesting to know in any case, even if we are to systematically doubt all the claims built around that core:

Rasika A. Mathias et al., Adaptive Evolution of the FADS Gene Cluster within Africa. PLoS ONE 2012. Open access ··> LINK [doi:10.1371/journal.pone.0044926]

Abstract

Long chain polyunsaturated fatty acids (LC-PUFAs) are essential for brain structure, development, and function, and adequate dietary quantities of LC-PUFAs are thought to have been necessary for both brain expansion and the increase in brain complexity observed during modern human evolution. Previous studies conducted in largely European populations suggest that humans have limited capacity to synthesize brain LC-PUFAs such as docosahexaenoic acid (DHA) from plant-based medium chain (MC) PUFAs due to limited desaturase activity. Population-based differences in LC-PUFA levels and their product-to-substrate ratios can, in part, be explained by polymorphisms in the fatty acid desaturase (FADS) gene cluster, which have been associated with increased conversion of MC-PUFAs to LC-PUFAs. Here, we show evidence that these high efficiency converter alleles in the FADS gene cluster were likely driven to near fixation in African populations by positive selection ~85 kya. We hypothesize that selection at FADS variants, which increase LC-PUFA synthesis from plant-based MC-PUFAs, played an important role in allowing African populations obligatorily tethered to marine sources for LC-PUFAs in isolated geographic regions, to rapidly expand throughout the African continent 60–80 kya.

Whether it is true that those fatty acids are so desperately needed for bigger brains or not really so much, allow me to remain healthily skeptic to begin with (any report on elephants for example, whose diet is purely vegetarian but do have big complex brains?)

I will also remain skeptic of the fact, which is implied by the study, of a primitive vegetarian or almost vegetarian diet of Homo sapiens in Africa: I do not think that such an a priori claim can stand at all. The same logic that applies in Africa should apply in Eurasia-plus but the fact is that Eurasians retain the ancestral allele and related genetic bloc without obvious damage to the brains.

There should be another explanation therefore: for example a founder effect at the Eurasian initial "out-of-Africa" bottleneck after a process of near fixation at previous, or maybe even adaptive introgression from Neanderthals in this aspect.

Finally the authors use absolutely wrong age estimates, all founded in that nonsense as is the molecular clock. According to the authors:

Studies suggest that anatomically modern humans arose in Africa approximately 150 thousand years ago (kya), expanded throughout Africa ~60–80 kya, and to most parts of Europe and Asia ~40 kya[1]–[6].

A paper that insists in such an obvious error should never pass the peer-review process, in my not-so-humble opinion.

Even if we ignore the absurdity of this molecular-clock-o-logic pseudoscientific insistence, and accept that we have to double or more than double the age estimates to be back into the common sense zone, or better, just ignore them altogether, we still have the problem of why would the allele and the whole genetic block around it be almost fixated in Africa but not at all in that African-derived subset that is Eurasia and the smaller continents.

Figure 3. Geographic distribution of derived allele frequencies in a 100 kb region surrounding rs174537 in the 52 populations represented in the Human Genome Diversity Panel Data. Panel A represents physical position of the SNPs relative to genes in the region, Panel B is SNP name (derived allele), Panel C is frequency of derived allele (in orange) in the populations clustered based on geography, Panel D is an indication of the allele associated with increased LC-PUFA metabolism in published association studies, and Panel E is the detailed overview of rs174537 showing is near fixation within Africa.

SNPedia reports slightly less dramatic levels of fixation in Africa for rs174537 itself but nothing that is too important.

So we do have a clear case of an allele that has been selected for in Africa but, crucially, not elsewhere. 

My highly skeptical questions are: 

1. How can this have happened in Africa prior to the migration out of Africa, as the authors claim, but not affect that African subset that was the migrant "out of Africa" population, whose formation necessarily happened after the African expansion and close to the overall origin(s) of that African expansion?
2. If the fixated allele is so important for brain function how is it that many Eurasians-plus, who lack the allele are not plainly dumb? How did they survive along time?
3. Do the authors have any archaeological evidence that vegetarian sources of food, notably oils, were so extremely important in African Middle Paleolithic (Middle Stone Age)? I do not think so, not at all.
4. How do the authors explain the lack of selection for this allele in South Asia, a region where total or almost total vegetarianism (dairies excepted) has been very common for many millennia.
5. How do the authors explain the lack of selection out of Africa or even what would seem to be a tendency for the opposite selection trend in parts of East Asia and Native America?

Actually the only well known adaptive role of this SNP is that it protects against cholesterol but not the allele that appears to have been selected in Africa but the "blue bloc" that survived out if it (and may have been selected for in some regions, speculatively). TT homozygotes, and only them, have lower LDL-C and total cholesterol.These are only truly common among SE Asians and Native Americans (or Mestizos).

So what do we make of this? In truth no idea: the authors hypothesis is there but I fail to find merit in most of it. It may be just a matter of refinement of the original hypothesis however - your take.

Wax' dental filling in Neolithic Slovenia

Figure 1.
The Lonche jaw.
Scale bar, 10 mm.

While dentists and their oversized bills are a modern development, ancient peoples also had to face the painful and sometimes deadly problems derived of damaged teeth. In some cases they found what seem to be acceptable home-made solutions:

Federico Bernardini et al. Beeswax as Dental Filling on a Neolithic Human Tooth. PLoS ONE 2012. Open access ··> LINK [doi:10.1371/journal.pone.0044904]

The authors mention previous findings in Pakistan (regularly modified cavities) as the actual known oldest record of non-extractive dentistry, dating to 7500-9500 years ago (Coppa et al. 2006) but this one seems to be the oldest record of effective preserved filling. 

The finding corresponds to an individual known as Lonche 1, found in the cave of Lonche in 1937 when the area was Italian territory (now it belongs to Slovenia) and preserved in the Natural History Museum of Trieste with a not of limited informative value about the context of the finding: Upper Pleistocene fauna, believed originally to be one of the oldest human findings in the region. 

However radiocarbon analysis performed directly on the bone provides an age of 6655-6400 cal. BP, corresponding to the Neolithic (Cardium Pottery, post-Vlaška phase). The authors provide us with a succinct description of the cultural context that I truly appreciate:

The area, at the northern shore of the Adriatic Sea, is rich in archaeological cave sites and rock shelters, many of which were occupied during recent prehistory and mainly used for stabling animals. In fact, the Neolithic economy of the karstic area was mainly based on sheep breeding [8]. The neolithization process spread through northern Istria and Trieste Karst in the middle of the 6^th millennium BC, coming from the south along the eastern Adriatic coast, and is referred to as the so-called Vlaška Culture. This culture shows connections with the Danilo Culture of central Dalmatia and the first Neolithic sites of the Friuli plain and lasts up to the beginning of the 5^th millennium BC. The post-Vlaška assemblages (5^th millennium BC) are not yet well understood and a clear chrono-cultural sequence is not available. It seems that there was no substantial change with respect to previous pottery shapes, some of which disappeared [9], [10]. However, a few and new typological elements suggest cultural affinities with Dalmatia (Hvar Culture) and northern Italy (Square Mouthed Pottery Culture).

Gut microbes can be decisive in fat accumulation

Credit: Image created by Ivana Semova, PhD

Certain gut microbes, known as Firmicutes, whose abundance varies from individual to individual, seem to be critical in fat absorption in the stomach and may be a major cause behind the obesity pandemic.

So far this has only been tested in zebrafish (a model organism not so different from us) but there are previous studies in humans that do suggest that the abundance of these microbes may be critical for us too. If so, it would explain how the long-term diet and not just the short-term one affects weight because the abundance of these bacteria would mostly be affected by long term trends, beginning in childhood.

Ivana Semova, Microbiota Regulate Intestinal Absorption and Metabolism of Fatty Acids in the Zebrafish. Host & Microbe 2012. Freely available at the time of this citation ··> LINK [doi:10.1016/j.chom.2012.08.003]

Main source: Science Daily. 

The other red cell disease that protects against the other malaria

Oval red cells
(CC The New Messiah)

It is generally well known that the sickle-cell disease, relatively common in parts of Africa, or rather its associated allele when heterozygous, has a protective effect against malaria, specifically to the variant caused by Plasmodium falciparium.

But there is at least another adaption to another kind of malaria: the one caused by P. vivax. This one, the SE Asian ovalocytosis (SAO), has only been discovered and studied in the last years and seems to exist only in some populations of Malaysia and Papua. This study confirms that the SAO defect effectively protects against P. vivax.

Ana Rosanas Urgell et al., Reduced Risk of Plasmodium vivax Malaria in Papua New Guinean Children with Southeast Asian Ovalocytosis in Two Cohorts and a Case-Control Study. PLoS Medicine 2012. Open access ··> LINK [doi:10.1371/journal.pmed.1001305] 

Abstract

Background

The erythrocyte polymorphism, Southeast Asian ovalocytosis (SAO) (which results from a 27-base pair deletion in the erythrocyte band 3 gene, SLC4A1Δ27) protects against cerebral malaria caused by Plasmodium falciparum; however, it is unknown whether this polymorphism also protects against P. vivax infection and disease.

Methods and Findings

The association between SAO and P. vivax infection was examined through genotyping of 1,975 children enrolled in three independent epidemiological studies conducted in the Madang area of Papua New Guinea. SAO was associated with a statistically significant 46% reduction in the incidence of clinical P. vivax episodes (adjusted incidence rate ratio [IRR] = 0.54, 95% CI 0.40–0.72, p<0.0001) in a cohort of infants aged 3–21 months and a significant 52% reduction in P. vivax (blood-stage) reinfection diagnosed by PCR (95% CI 22–71, p = 0.003) and 55% by light microscopy (95% CI 13–77, p = 0.014), respectively, in a cohort of children aged 5–14 years. SAO was also associated with a reduction in risk of P. vivax parasitaemia in children 3–21 months (1,111/µl versus 636/µl, p = 0.011) and prevalence of P. vivax infections in children 15–21 months (odds ratio [OR] = 0.39, 95% CI 0.23–0.67, p = 0.001). In a case-control study of children aged 0.5–10 years, no child with SAO was found among 27 cases with severe P. vivax or mixed P. falciparum/P. vivax malaria (OR = 0, 95% CI 0–1.56, p = 0.11). SAO was associated with protection against severe P. falciparum malaria (OR = 0.38, 95% CI 0.15–0.87, p = 0.014) but no effect was seen on either the risk of acquiring blood-stage infections or uncomplicated episodes with P. falciparum. Although Duffy antigen receptor expression and function were not affected on SAO erythrocytes compared to non-SAO children, high level (>90% binding inhibition) P. vivax Duffy binding protein–specific binding inhibitory antibodies were observed significantly more often in sera from SAO than non-SAO children (SAO, 22.2%; non-SAO, 6.7%; p = 0.008).

Conclusions

In three independent studies, we observed strong associations between SAO and protection against P. vivax malaria by a mechanism that is independent of the Duffy antigen. P. vivax malaria may have contributed to shaping the unique host genetic adaptations to malaria in Asian and Oceanic populations.

Autism does not have genetic causes

Not a single SNP was found to influence the development of autism spectrum disorders in an ample GWAS study:

Richard Anney et al., Individual common variants exert weak effects on the risk for autism spectrum disorderspi. Human Molecular Genetics 2012. Open access ··> LINK [doi: 10.1093/hmg/dds301]

Abstract

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.

A synthetic report on this paper may be found at The Spitoon.

This study seems to effectively discard any major genetic influence in autism and forces us to look again for environmental clues like environmental pollutants, pregnancy conditions, early parental care (such as breastfeeding), vaccines, etc. in order to understand the causes behind these problems. Per Wikipedia:

Environmental factors that have been claimed to contribute to autism or exacerbate its symptoms, or may be important to consider in future research, include certain foods, infectious disease, heavy metals, solvents, diesel exhaust, PCBs, phthalates and phenols used in plastic products, pesticides, brominated flame retardants, alcohol, smoking, illicit drugs, and vaccines.

Common pollutants, notably many common plastics, pesticides, etc., are high among the likely causes of the disorders, as well as many other modern diseases.

Lactose tolerance favors obesity

While the lactose tolerance allele may have some positive health effects, notably because milk is one of the few good dietary sources of calcium, it seems to correlate also with some negative effects, namely obesity.

Ricardo Almon et al., Association of the European Lactase Persistence Variant (LCT-13910 C>T Polymorphism) with Obesity in the Canary Islands. PLoS ONE 2012. Open access ··> LINK [doi:10.1371/journal.pone.0043978]

Canary Islands, in spite of its subtropical geography, is one of the regions of the European Union where milk is most consumed, at levels comparable to Scandinavia. 

Although there is a strong correlation between being lactose tolerant and milk consumption it is not fully clear yet if it is excess milk consumption what makes people obese or an unknown collateral effect of the European lactase persistence allele.

Interestingly the correlation, very strong, is only found for obesity and not for being overweight:

Fig. 1 - BMI classification by LCT genotypes (LP: n = 330; LNP: n = 221)

Some chimp-human differences are epigenetic

Nothing related to brain function this time but rather to attributes that our jungle cousins seem to be at advantage compared to us. Notably chimpanzees almost never have cancer or some other diseases, like mental disorders, which we suffer a lot. This new research suggests it may be because of low methylation levels in humans (i.e. epigenetics, hinting at environmental causes rather than pure inheritance).

Jia Zeng et al., Divergent Whole-Genome Methylation Maps of Human and Chimpanzee Brains Reveal Epigenetic Basis of Human Regulatory Evolution. AJHG 2012. Pay per view (free after 6 months embargo) ··> LINK [doi:10.1016/j.ajhg.2012.07.024]

Abstract

DNA methylation is a pervasive epigenetic DNA modification that strongly affects chromatin regulation and gene expression. To date, it remains largely unknown how patterns of DNA methylation differ between closely related species and whether such differences contribute to species-specific phenotypes. To investigate these questions, we generated nucleotide-resolution whole-genome methylation maps of the prefrontal cortex of multiple humans and chimpanzees. Levels and patterns of DNA methylation vary across individuals within species according to the age and the sex of the individuals. We also found extensive species-level divergence in patterns of DNA methylation and that hundreds of genes exhibit significantly lower levels of promoter methylation in the human brain than in the chimpanzee brain. Furthermore, we investigated the functional consequences of methylation differences in humans and chimpanzees by integrating data on gene expression generated with next-generation sequencing methods, and we found a strong relationship between differential methylation and gene expression. Finally, we found that differentially methylated genes are strikingly enriched with loci associated with neurological disorders, psychological disorders, and cancers. Our results demonstrate that differential DNA methylation might be an important molecular mechanism driving gene-expression divergence between human and chimpanzee brains and might potentially contribute to the evolution of disease vulnerabilities. Thus, comparative studies of humans and chimpanzees stand to identify key epigenomic modifications underlying the evolution of human-specific traits.

See also the article at Science Daily.