Poverty directly damages brain development

Children that at early ages have similar or even greater gray matter than their wealthier peers, get stuck in a weaker development as they grow just for being poor. That is what a new study has found:

Jamie L. Hanson et al., Family Poverty Affects the Rate of Human Infant Brain Growth. PLoS ONE 2013. Open access → LINK [doi:10.1371/journal.pone.0080954]

Abstract

Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems.

Figure 2. This figure shows total gray matter volume for group by age.

The data is clear (for details of the localized frontal and parietal evolution see figs. 3 and 4). The question is: why does this happen? The paper attempts also to discuss that:

These results extend a consistent literature in rodents, non-human primates, and humans suggesting that early environments marked by stress or deprivation negatively influence brain development [65]–[69]. This emerging body of research has found differences in brain structure in portions of the frontal lobe, which fits well with the analysis presented here [68]. These findings suggest that aspects of low SES environments have important functional implications for children's health and adaptation [70], perhaps by influencing key features of central nervous system development. In regards to neurobiological mechanisms, the differences in volume we find are likely due to neuronal remodeling, rather than birth of new neurons (or neurogenesis) [27], [71], [72].

(...)

Candidate factors might include the effects of household resources, environmental stimulation, crowding, exposure to pathogens and noise, parental stress, and nutrition. It is also possible that pre-natal experiences affect brain development and reflect other disadvantages and risks related to poverty. Because humans are able to adapt to a range of environmental conditions, we must understand more about the level at which impoverished environments become toxic for children.

And quite suggestively in the introduction they mention as well that:

Conditions such as the variety and complexity of the stimuli in an animal's cage can influence different aspects of brain structure, including the number of neurons, glial cells, myelination, dendrites, synapses, and neurogenesis (for review, see Ref. [23]–[24]). 

The specific causes can be many but I'd dare say that "caging", i.e. the limitation of stimuli for living in smaller, impoverished, artificial habitats (including of course whatever limitations that the adults around them may have, such as low culture or emotional instability) is likely to be a key negative environmental factor for brain development.

On the other hand I can imagine that certain enrichment (cultural, health even technological, why not?) that has happened to our species in general in the last centuries, may be behind the so-called Flynn effect, which is that the measured IQ has been growing everywhere quite steadily. 

But in any case it is quite worrying that these social differences have such a big effect on the children and emphasizes the need to overcome them and to provide the best possible environment for the development of the future generations.

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.

Plants do use epigenetics to adapt to diverse environments

If you've ever grown plants that come from a distant land, you may be familiar with the fact that you may need an adaptive process of one or more generations to get the best of them. Oddly enough this time is often too short for genetic adaption to happen and sweep over, especially as most of the ill-adapted plants don't really die nor fail to reproduce (i.e. they are not too aggressively selected against). How does it happen then? Epigenetics may have the answer.

Robert J. Schmidt et al., Patterns of population epigenomic diversity. Nature 2013. Pay per view → LINK [doi:10.1038/nature11968]

Abstract

Natural epigenetic variation provides a source for the generation of phenotypic diversity, but to understand its contribution to such diversity, its interaction with genetic variation requires further investigation. Here we report population-wide DNA sequencing of genomes, transcriptomes and methylomes of wild Arabidopsis thaliana accessions. Single cytosine methylation polymorphisms are not linked to genotype. However, the rate of linkage disequilibrium decay amongst differentially methylated regions targeted by RNA-directed DNA methylation is similar to the rate for single nucleotide polymorphisms. Association analyses of these RNA-directed DNA methylation regions with genetic variants identified thousands of methylation quantitative trait loci, which revealed the population estimate of genetically dependent methylation variation. Analysis of invariably methylated transposons and genes across this population indicates that loci targeted by RNA-directed DNA methylation are epigenetically activated in pollen and seeds, which facilitates proper development of these structures.

From the body of the article:

Epiallele formation in the absence of genetic variation can result in phenotypic variation, which is most evident in the plant kingdom, as exemplified by the peloric and colorless non-ripening variants from Linaria vulgaris and Solanum lycopersicum, respectively^{6, 7}. Although rates of spontaneous variation in DNA methylation and mutation can be decoupled in the laboratory^{8, 9, 10, 11}, in natural settings, these two features of genomes co-evolve to create phenotypic diversity on which natural selection can act.

...

Similarly to the limited examples of pure epialleles (methylation variants that form independent of genetic variation), few examples of DNA methylation variants linked to genetic variants are known^{15, 16, 17}.

And the 'Conclusion remarks' (emphasis is mine):

Natural epigenomic variation is widespread within A. thaliana, and the population-based epigenomics presented here has uncovered features of the DNA methylome that are not linked to underlying genetic variation, such as all forms of SMPs and CG-DMRs. However, C-DMRs have positional association decay patterns similar to linkage disequilibrium decay patterns for SNPs and in some cases are associated with genetic variants, but the majority of C-DMRs were not tested by association mapping due to low allele frequencies and could result from rare sequence variants. Our combined analyses of genetic and methylation variation did not uncover a correlation between major effect mutations and genes silenced by RdDM, suggesting that this pathway may target these genes for another purpose. This purpose could be to restrict expression from vegetative tissues similarly to transposons. Another possible purpose of being targeted by RdDM could be to coordinate expression specifically in pollen and in seed to ensure proper gametophytic and embryonic development. Animals also use small RNA-directed DNA methylation and heterochromatin formation mechanisms to maintain the epigenome of the germ line through the use of Piwi-interacting RNAs³⁶. In both plants and animals these small RNAs are derived from the genome of companion cells, which are terminal in nature and can afford widespread reactivation of transposon and repeat sequences as they are not passed on to the next generation. Our study provides evidence that RdDM-targeted genes may have co-opted this transposon silencing mechanism to maintain their silenced state in vegetative tissues and transgenerationally, as well as to ensure proper expression important for pollen, seed and germ line development.

Emotional care or neglect of young children decisive for brain size, intelligence

An image says more than a thousand words. And in this case the image is a brain scan... or rather two side by side:

Both brains belong to 3-years-old children

... the child with the shrunken brain was neglected and abused by its mother, and the child with the larger and more fully developed brain was raised in a loving, supportive home and was looked after by its mother...

This is not just about IQ or head size, which may vary at least largely because of this type of environmental causes, but about everything in life, including emotional and social intelligence and the general ability to carry on with a normal, well integrated life (or become human waste). 

The first years of life are critical for all our development and parental love, very specially that of our mothers, is probably more important than almost anything else.

Source: Medical Daily.

Epigenetics and IQ variability

A new study on monozygotic (identical) twins with clear IQ differences finds that epigenetic methylation of certain genes may be the cause:

Chih-Chieh Yu, Genome-Wide DNA Methylation and Gene Expression Analyses of Monozygotic Twins Discordant for Intelligence Levels. PLoS ONE, 2012. Open access ··> LINK [doi:10.1371/journal.pone.0047081]

Abstract

Human intelligence, as measured by intelligence quotient (IQ) tests, demonstrates one of the highest heritabilities among human quantitative traits. Nevertheless, studies to identify quantitative trait loci responsible for intelligence face challenges because of the small effect sizes of individual genes. Phenotypically discordant monozygotic (MZ) twins provide a feasible way to minimize the effects of irrelevant genetic and environmental factors, and should yield more interpretable results by finding epigenetic or gene expression differences between twins. Here we conducted array-based genome-wide DNA methylation and gene expression analyses using 17 pairs of healthy MZ twins discordant intelligently. ARHGAP18, related to Rho GTPase, was identified in pair-wise methylation status analysis and validated via direct bisulfite sequencing and quantitative RT-PCR. To perform expression profile analysis, gene set enrichment analysis (GSEA) between the groups of twins with higher IQ and their co-twins revealed up-regulated expression of several ribosome-related genes and DNA replication-related genes in the group with higher IQ. To focus more on individual pairs, we conducted pair-wise GSEA and leading edge analysis, which indicated up-regulated expression of several ion channel-related genes in twins with lower IQ. Our findings implied that these groups of genes may be related to IQ and should shed light on the mechanism underlying human intelligence.

The list of genes with a detectable effect is as follows:

Table 2. List of genes having the same tendency of expression level in most twin pairs.

It's worth noticing that a recent study (Chabris 2012) reviewing the literature found that most or maybe even all alleged genetic influences in intelligence are probably false positives (discussed here). Therefore is probable that many (most?, all?) differences in intelligence are caused by environmental influences, often manifested in epigenetic modifications like the ones detected in this study.

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.

Epigenetic alterations by pollutants heritable across generations

We are just learning how epigenetic alterations do not just affect the individual but can be as inheritable as DNA, at least for some generations, blurring the distinctions between heredability and environment. A new study found that all tested chemical pollutants caused inheritable epigenetic alterations:

Mohan Manikkam, Carlos Guerrero-Bosagna et al., Transgenerational Actions of Environmental Compounds on Reproductive Disease and Identification of Epigenetic Biomarkers of Ancestral Exposures. PLoS ONE 2012. Open access.

Abstract


Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1–F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease.

The most strongly demonstrated transgenerational effect is the early onset of puberty in females. Oddly enough it seems caused by the father's sperm.

According to SD:

The field opens new ground in the study of how diseases develop. While toxicologists generally focus on animals exposed to a compound, Skinner's work further demonstrates that diseases can also stem from older, ancestral exposures that are then mediated through epigenetic changes in sperm.

See also: category 'Epigenetics' in this and my old blog. 

Echoes from the Past (Nov 1)

Happy calaca day to all Mexicans. I have a bunch of interesting news items stored in the "to do" folder and it's time to release them in bulk and, in a sense, get rid of them that way. Hope you find them interesting.

Prehistory and proto-history:

Abalone ochre container from Blombos

I already commented in the previous 'Echoes' edition but the 100,000 years-old paint containers made-out-of-shells found in Blombos (South Africa) have been echoing through various media, each with a  slightly different twist ··> The Heritage Journal, MSNBC, SD.

Nail in the coffin for 'Clovis first' theory: mammoth bone spear point in mammoth leg bone dated precisely to pre-Clovis times: 13,800 years ago (there are older dates out there anyhow) ··> BBC.

Jaw bone found near Kennewick Man's site (and controversy on native insistence on reburial) ··> KPLU.

Cishan-Peligang pottery

Chinese Neolithic may be almost as old as West Asian one. Evidence of millet cultivation in Hebei (North China) dates to c. 10,000-8,700 years ago, within the Cishan culture (notice that Pengtoushan culture in South China overlaps with these dates and could be even quite older) ··> Xinhua. 

Bronze Age take-out windows found in Iran (Godin Tepe) ··> Unreported Heritage News, Live Science.

A new report on Iruña-Veleia Roman era graffiti supports their authenticity ··> Ostraka euskalduna[eu], where you can download the PDF in Spanish language by M. Thomson.

Also mentioned recently but still hitting the news, controversy on the reopening of Altamira cave, dubbed the Magdalenian Sistine Chapel, to the public ··> SD.

Replica of the Altamira ceiling (fragment)

Genetics:

Sardinian genetics point to pre-Neolithic origins according to new research (this I want to discuss in some greater detail but I'm sadly leaving for tomorrow again) ··> Daniela Contu et al. at PLoS ONE (open access). 

Researchers claim that mtDNA age estimates support pre-Neolithic dates for major East Asian population expansion ··> Hong-Xiang Zheng et al. at PLoS ONE (open access).

Fractal analysis of the human genome. You would think that putting together the words fractal and human genetics would appeal to my interest a lot. I must be getting old because it only does somewhat. A reason may be that while the methodology is intriguing and innovative no particular conclusion is proposed ··> Pedro A. Moreno et al. at BMC Genomics (open access).

Extra copies of SRGAP2 gene may be one reason behind human unique intelligence ··> Science News.

Human brains designed by the same fixated genes, regardless of race or individual differences. This is one of a list of novel findings on how the genome expresses in the brain along human life ··> SD.

Epigenetically modified nucleotide ("sixth letter" 5-hydroxymethylcytosine) in neuronal genomes is key to their behavior as such ··> SD.

Propensity for longer life inherited epi-genetically through generations. This so much coveted trait is inherited by lab roundworms even if the initial epigenetic modification has vanished ··> SD.

Other anthropology news:

Human children, but not chimpanzees, prefer to collaborate in order to solve tasks ··> Science Daily.

IQ is not totally fixed by genetics and can indeed change, specially in adolescence ··> BBC.

Other science news:

Comet storm detected in nearby stellar system (may increase chances of life by feeding planets like ours with water) ··> SD.

Nature laws may vary across the universe. At least electromagnetic constants seem to behave that way ··> PhysOrg.

Highly efficient (10x) hydrolysis catalyst found, helping to pave the way for easier production of hydrogen for fuel instead of dirty oil ··> SD.

Global warming is for real (in case you still had any doubt) ··> SD.

Echoes from the past (Sep 24)

And all the rest of the cool stuff in short headlines:

Archaeology and hominin evolution:

Robust australopithecines were indeed relatives, shows CT scan ··> SD.

Neanderthals also exploited seafood resources, as early as H. sapiens ··> El Neandertal tonto ¡qué timo![es].

Looters and bureaucracy destroy a Solutrean site in Andalusia (Higueral-Guardia cave). Sadly enough, it was a lot easier for looters to access the unprotected cave illegally than for archaeologists to do so legally ··> Pileta de Prehistoria[es].

What more classical troglodyte imagery than skulls on sticks? Sadly archaeology had never produced such artifacts... until now: Epipaleolithic Swedes had them ··> Pileta de Prehistoria[en].

Fascinating 'Nazca lines' found in Arabia ··> Live Science.

More Neolithic remains from Yesilova (Izmir, Turkey) ··>  Daily News.

Remember the first pampooty shoe (or abarka) found in Areni 1 cave (Armenia)? It has now also produced a skirt ··> News.am.

Bronze Age's stone anchors from the Black Sea ··> Novinite.

Fscinating 3D reconstructions of Stonehenge, Woodhenge, etc. ··> The Heritage Journal.

Stanton Drew reconstruction

Cahokia Mounds researched in some depth finally ··>  BND.

Clay disks from Alaska ··> Art Daily.

 

Genetics:

A. thaliana

Bronze Age haploid DNA from North China yields no surprises (mtDNA: D4, D*, M7c, A4, F1b, G1a, M9a, M10 and M8z; Y-DNA: N1c and O3) ··> Dienekes.

First Aboriginal Australian genome sequenced ··> Dienekes.

Epigenetic evolution: Arabidopsis thaliana does it all the time, what about humans? ··> SD.

Other sciences:

Quite impressive stuff these days:

Speed of light may not be the ultimate speed limit: neutrinos found going faster. It also challenges the unidirectionality of time ··> Al Jazeera, BBC.

LHC, where the barriers of science are broken

Dark matter challenged by dwarf galaxies ··> BBC.

Dwarf galaxy getting cocky

Special thanks to Stone Pages' Archaeo News section.

Many interesting short news

Partly because of the arrival of the Archaeo News bulletin but also because of mere randomness, it seems to me, a lot of more or less interesting news items are accumulating. In most cases I lack the information to deal with them in any greater depth but are still interesting to read about:


Genetics

Study suggests that the populations leading to modern Africans and Non-Africans did keep mixing for some 40,000 years before a Non-Africans suffered a severe bottleneck and became truly separated. This period of early divergence with interaction could have begun c. 120,000 or 100,000 years ago and would have ended c. 80-60 Ka ago. It could add support to the idea that Toba explosion caused a bottleneck. I'd like to write more about this but I have no access to the paper. -> Science Daily, -> Nature (PPV).

Inheritable epigenetics confirmed: may explain how living beings of all sorts adapt to changing conditions without need to alter their genetic backbone (DNA). -> Science Daily.


Human evolution

Chimpanzee brains do not shrink with age. Unlike humans, chimpanzee do not suffer the array of symptoms we loosely call senility, this may be therefore a hidden cost of having such large brains and living for so long. -> Science News.



Archaeology

Heacham burial

Magdalenian Age erotic art found in Bavaria (Germany). The unusual rock art was found near Bamberg and are believed to be c. 12,000 years old. It seems that the natural shapes in thecave may have inspired the ancient artists. -> news.com.au (no images provided).

Epipaleolithic open air cemetery found in Somerset (England). It is dated to c. 10,000 years ago. -> BBC.

England: Sheffield 6000 BCE: people lived continuously at nearby Whirlow Hall Farm since the Epipaleolithic and into the Iron Age. -> The Star. 

5000 years-old skeleton unearthed in Aosta Valley (Italy). The woman has been nicknamed Lady of Introd and was more or less contemporary of Ötzi the iceman, found frozen in Tyrol years ago. -> Archaeo News.

Tall el-Hammam pottery

And more England findings: burial of two women with amber beads found in Yorkshire, near Heacham, and dated to c. 2500 BCE (late Neolithic by British chronology, Chalcolithic by pan-European standards). -> EDP24.

Egyptian Old Kingdom may have succumbed to drought, suggests geological survey at Lake Tana (Ethiopia) at the source of the Blue Nile (the main contributor to the Nile in volume and the responsible of seasonal floods). -> PhysOrg.

Bronze and Iron Age city unearthed in Jordan, NE of the Dead Sea (near modern Kafrein, just across the Jordan river from Jerico). -> Tall el-Hammam (dig site), -> Popular Archaeology.

Three genetic papers

Follow titles, links and abstracts of three open access genetic papers that I feel are interesting enough to mention but are too technical and distant from my main focus to be discussed meaningfully here:

What is a species? The example of lemurs

Matthias Markoff et al., On species delimitation: Yet another lemur species or just genetic variation? BMC Evolutionary Biology 2011. [LINK]

Abstract (provisional)

Background

Although most taxonomists agree that species are independently evolving metapopulation lineages that should be delimited with several kinds of data, the taxonomic practice in Malagasy primates (Lemuriformes) looks quite different. Several recently described lemurs are based solely on evidence of genetic distance and diagnostic characters of mitochondrial DNA sequences sampled from a few individuals per location. Here we explore the validity of this procedure for species delimitation in lemurs using published sequence data.

Results

We show that genetic distance estimates and Population Aggregation Analysis (PAA) are inappropriate for species delimitation in this group of primates. Intra- and interspecific genetic distances overlapped in 14 of 17 cases independent of the genetic marker used. A simulation of a fictive taxonomic study indicated that for the mitochondrial D-loop the minimum required number of individuals sampled per location is 10 in order to avoid false positives via PAA.

Conclusions

Genetic distances estimates and PAA alone should not be used for species delimitation in lemurs. Instead, several nuclear and sex-specific loci should be considered and combined with other data sets from morphology, ecology or behavior. Independent of the data source, sampling should be done in a way to ensure a quantitative comparison of intra- and interspecific variation of the taxa in question. The results of our study also indicate that several of the recently described lemur species should be reevaluated with additional data and that the number of good species among the currently known taxa is probably lower than currently assumed.

Horizontally acquired genes: breaching the gate is not getting the treasure automatically, you may also end in the dungeons

H. Deborah Chen et al., Ancestral Genes Can Control the Ability of Horizontally Acquired Loci to Confer New Traits. PLoS Genetics 2011. [LINK]

Abstract

Horizontally acquired genes typically function as autonomous units conferring new abilities when introduced into different species. However, we reasoned that proteins preexisting in an organism might constrain the functionality of a horizontally acquired gene product if it operates on an ancestral pathway. Here, we determine how the horizontally acquired pmrD gene product activates the ancestral PmrA/PmrB two-component system in Salmonella enterica but not in the closely related bacterium Escherichia coli. The Salmonella PmrD protein binds to the phosphorylated PmrA protein (PmrA-P), protecting it from dephosphorylation by the PmrB protein. This results in transcription of PmrA-dependent genes, including those conferring polymyxin B resistance. We now report that the E. coli PmrD protein can activate the PmrA/PmrB system in Salmonella even though it cannot do it in E. coli, suggesting that these two species differ in an additional component controlling PmrA-P levels. We establish that the E. coli PmrB displays higher phosphatase activity towards PmrA-P than the Salmonella PmrB, and we identified a PmrB subdomain responsible for this property. Replacement of the E. coli pmrB gene with the Salmonella homolog was sufficient to render E. coli resistant to polymyxin B under PmrD-inducing conditions. Our findings provide a singular example whereby quantitative differences in the biochemical activities of orthologous ancestral proteins dictate the ability of a horizontally acquired gene product to confer species-specific traits. And they suggest that horizontally acquired genes can potentiate selection at ancestral loci.

Author Summary

The traits that distinguish closely related bacterial species are often ascribed to differences in gene content, which arise primarily through horizontal gene transfer. In some instances, the genes mediating a new trait act as independent entities that function in a variety of organisms. However, the ability of a horizontally acquired gene product(s) to operate on an ancestral pathway might be constrained by subtle differences between orthologous ancestral proteins. Here, we examine why the horizontally acquired pmrD gene product post-translationally activates the ancestral PmrA/PmrB two-component system in Salmonella enterica but not in the closely related species Escherichia coli. This allows Salmonella, but not E. coli, to transcribe PmrA-activated genes including those conferring antibiotic resistance when grown in low Mg2+, which is a condition that promotes PmrD expression. We now demonstrate that, paradoxically, the E. coli PmrD protein activates the PmrA/PmrB system in Salmonella even though it fails to do so in E. coli. We establish that quantitative differences in the biochemical activities of the PmrB proteins from Salmonella and E. coli dictate the functionality of PmrD, which protects phosphorylated PmrA from PmrB's phosphatase activity. Our findings demonstrate that ancestral genes can control the ability of horizontally acquired genes to confer species-specific traits upon different organisms.

Day and night cycle in our cells, the clock inside us and its epigenetic synchronization

William J. Belden et al., CHD1 Remodels Chromatin and Influences Transient DNA Methylation at the Clock Gene frequency. PLoS Genetics 2011. [LINK]

Abstract

Circadian-regulated gene expression is predominantly controlled by a transcriptional negative feedback loop, and it is evident that chromatin modifications and chromatin remodeling are integral to this process in eukaryotes. We previously determined that multiple ATP–dependent chromatin-remodeling enzymes function at frequency (frq). In this report, we demonstrate that the Neurospora homologue of chd1 is required for normal remodeling of chromatin at frq and is required for normal frq expression and sustained rhythmicity. Surprisingly, our studies of CHD1 also revealed that DNA sequences within the frq promoter are methylated, and deletion of chd1 results in expansion of this methylated domain. DNA methylation of the frq locus is altered in strains bearing mutations in a variety of circadian clock genes, including frq, frh, wc-1, and the gene encoding the frq antisense transcript (qrf). Furthermore, frq methylation depends on the DNA methyltransferase, DIM-2. Phenotypic characterization of Δdim-2 strains revealed an approximate WT period length and a phase advance of approximately 2 hours, indicating that methylation plays only an ancillary role in clock-regulated gene expression. This suggests that DNA methylation, like the antisense transcript, is necessary to establish proper clock phasing but does not control overt rhythmicity. These data demonstrate that the epigenetic state of clock genes is dependent on normal regulation of clock components.

Author Summary

Circadian rhythms facilitate daily changes in gene expression via a transcriptional negative feedback loop. In eukaryotes, chromatin remodeling is an integral part of transcriptional regulation and is proving to be one of the major determinants for the proper timing and amplitude of clock-gene expression. We describe here the action of chromodomain helicase DNA–binding (CHD1), one of two ATP–dependent chromatin-remodeling enzymes required for normal circadian regulated gene expression of the central clock gene frequency (frq). Molecular analysis of strains lacking chd1 indicates that CHD1 is required for remodeling chromatin structure at the frq locus as a part of the daily clock cycle. Moreover, we discovered DNA methylation in the promoter of frq that diminishes over time in the absence of light/dark cycles and determined that normal DNA methylation appears to require a functional clock. The DNA methyltransferase DIM-2 is responsible for this DNA methylation, and the DNA methylation is required for proper phasing of clock gene expression. Collectively, these data demonstrate a close connection among chromatin remodeling, DNA methylation, and clock gene expression.

Season of birth affects circadian clock

At least in mice, season of birth seems to imprint behavioral cue, affecting the circadian clock (internal time schedule). Some of the effects are notoriously similar to some disorders observed in humans, suggesting that the effect may be extensive to our species (not so distant from mice anyhow). 

Cristopher M. Chiarello et al., Perinatal photoperiod imprints the circadian clock. Nature Neuroscience, 2010. 

A maybe more easy to comprehend press release is available at Science Daily.

The effects of the environment on the expression of our genes seems to be quite extensive. While we still know too little, there is some steady advance in this most intriguing research field.

While the principal finding is technically limited to the circadian clock its overall effects may be more ample. Co-researcher Douglas McMahon explained that:

We know that the biological clock regulates mood in humans. If an imprinting mechanism similar to the one that we found in mice operates in humans, then it could not only have an effect on a number of behavioral disorders but also have a more general effect on personality.

While it seems easy to compare with simple Astrology, McMahon warns:

It's important to emphasize that, even though this sounds a bit like astrology, it is not: it's seasonal biology!

Well... whatever. What matters is that there is empirical evidence for a quantifiable imprinting effect of psycho-biological effect that is determined by season of birth, and that the extent of this environmental modulation may well extend to all the psyche, affecting the personality. 

But if this happens and exactly how is yet to be researched.

Some population structured SNPs and also one epigenetic factor

Another more complex, yet still interesting, paper related with population structure in this last issue of PLoS ONE is:

Jingyu Liu et al., Identification of Genetic and Epigenetic Marks Involved in Population Structure. PLoS ONE 2010. Open Access. 

They have detected some SNPs, mostly related to appearance, that seem to weight specially high in population structure at global levels. Interestingly they have also located an epigenetic marker that weights somewhat in the European+African vs. East Asian+Native American axis.

The most relevant population structure SNPs are by this order:

1. Rs16891982, strongly related to the West Eurasian type of depigmentation (SLC45A2), and logically structured along the West Eurasian-Others axis in an almost true/false type of structure, excepting admixed populations.
2. Rs535878, not yet reported at SNPedia. It is structured along the Native American vs. African American+East Asian axis, with West Eurasians and admixed populations being intermediate (but closer to Native Americans). So Native Americans (and West Eurasians to some extent) seem to have the derived allele.
3. Rs13013484, again not reported in SNPedia yet. The structure runs between African Americans and East Asians. With other populations being intermediate (but except Latinos all closer to African Americans). So East Asians (specially) have the derived allele. However notice that the East Asian sample of just one individual is somewhat inconclusive.

There are more SNPs pondered (see table 1) with factor ranking 22nd being 48 methylation sites in 44 genes of 18 chromosomes, affecting specially West Eurasians and Native Americans in opposite senses. In particular the PM20D1 methylated site seems to have some weak but significant selective pressure among West Eurasians (and admixed populations) - see fig.2B.