Category Archives: Genetics

Echoes from the past (May-9-2013)

I am getting updated with a rather long backlog, so I will speed things up placing here in nearly telegraphic style the informative snippets that require less work. This does not mean that they are less interesting, not at all, just that I have to adapt to that elusive quality of time…

Middle Paleolithic

Toba supervolcano only had short-term climate effectBBC.
Research on Lake Malawi’s sediments shows that the climate-change effect of the catastrophic eruption was limited. Droughts previously believed to be from that period have been revised to be from at least 10,000 years before, corresponding to the end of the Abbassia Pluvial rather than to Toba super-eruption.

Upper Paleolithic

Altai rock art and early astronomy from 16,000 BPSiberian Times, Daily Mail.
Sunduki (Khakassia), here there are what are surely the oldest rock art of Northern Asia, representing people hunting or interacting among them, which are from just centuries ago, however other petroglyphs are apparently much older like this horse:

Prof. Vitaly Larichev (Institute of Archeology and Ethnography, Russian Academy of Sciences) has detected a whole astronomical structure implemented in the landscape.

He claims to have found ‘numerous ancient solar and lunar observatories around Sunduki’.

‘This square pattern of stones on the ground shows you the place’, he
told visiting author Kira Van Deusen. ‘I knew there would be an
orientation point, but we had to search through the grass for a long
time to find it.

‘Now look up to the top of that ridge. You see a place where there is
a crack between the rocks? If you were here on the summer solstice, you
would see the sun rise right there. Or you would if you were here 2,000
years so. Now the timing is slightly differen’.

High on one cliff wall is a rock engraving showing dragon heads in one direction, and snake heads in the other.

‘If the sun were shining, we could tell the time,’ he said. ‘In the
morning the shadow moves along the snake’s body from his head to his
tail, and in the afternoon it comes from the other direction along the

‘From the same observation point you can determine true north and south by sighting along the mountains’.


Vietnam: early cemetery dug in Thahn HoaAustralian National University.
Some 140 human remains of all ages have been unearthed at the site of Con Co Ngua, estimated to be 6-4000 years old. Cemeteries of this size and age were previously unknown in the region. The site has also revealed a dearth of artifacts. 
The people were buried in fetal position with meat cuts of buffalo or deer.


India: 4000 y.o. stone tools unearthed in Bhopal (Madhya Pradesh, Narmada river)India Today.
  • Some of them are decorated with aquatic animals.
  • 150×200 m. mound in Birjakhedi
  • Terracotta game pieces
  • Pottery (incl. jars, pots, dishes)
  • Stone and ivory beads
Bell Beaker rich lady’s burial unearthed in Berkshire (England)Wessex Archaeology.
The middle-aged woman wore a necklace of tubular golden beads, amber buttons on her clothes and a possible lignite bracelet. She was accompanied by a bell-shaped beaker of the “corded” type (oldest and roughest variant, of likely Central European inception).
The chemical signature of the gold beads is coherent with deposits from Southern Britain and SE Ireland. 

Giza pyramid construction’s logistics revealed Live Science.

Caesar beat the Gauls.
Was there not even a cook in his army?

Bertolt Brecht (A Worker reads History)

Now we know that at the very least the famed early pharaohs Khafra, Khufu and Menkaure, who ordered the massive pyramids of Giza to be built as their tombs did have some cooks in charge of feeding the many workers who actually built them, stone by stone. 
These workers were housed in a village some 400 meters south of the Sphinx, known as Heit el-Ghurab. In this place archaeologists have found a cemetery, a corral with apparent slaughter areas and piles of animal bones. Based on these, researchers estimate that more than 2,000 kilograms of meat were eaten every day during the construction of Menkaure’s pyramid, the last and smallest one of the three geometric mounds. 
The figures estimated for such a logistic operation border disbelief: 22,000 cows, 55,000 sheep and goats, 1200 km² of grazing land (roughly the size of Los Angeles or 5% of the Nile Delta), some 3500 herders (adding up to almost 20,000 people if we include their families). 
A curious detail is that most of the beef was destined to the building of the overseers, while the common workers were mostly fed sheep or goat instead. Another settlement to the East of apparently local farmers ate most of the pork. There were also temporary tent camps closer to the pyramids.

Iron Age

Late Indus Valley Civilization was overcome by violenceNational Geographic.

Harappa (CC by Shephali11011)
The Late Indus Valley Civilization (Cemetery H cultural layer, usually attributed to the Indoeuropean invasions) was, unlike in previous periods, quite violent, new evidence highlights. 
The evidence from the bones also highlights the arrival of many non-local men, who apparently married local women. But the most shocking element is the striking evidence of widespread violence:

The skull of a child between four and six years old was
cracked and crushed by blows from a club-like weapon. An adult woman was
beaten so badly—with extreme force, according to researchers—that her
skull caved in. A middle-aged man had a broken nose as well as damage
to his forehead inflicted by a sharp-edged, heavy implement.
Of the 18 skulls examined from this time period, nearly half showed serious injuries from violence …

Gaming pieces of Melton Mowbray (England)Science Daily.

Excavation of a hillfort at Burrough Hill revealed ancient gaming pieces, among other materials. 

Funerary chamber found near the original location of the Lady of Baza (Andalusia)Paleorama[es].

(CC by P.A. Salguero Quiles)
The tomb has an access gate and is estimated to be from the 5th or 4th centuries BCE (Iberian culture) and, unlike most burials of the time, the corpse was not incinerated. 
The finding highlights the need for further archaeological work in all the hill but the severe budgetary cuts threaten this development. 
Baza (Granada) hosts a dedicated archaeological museum inaugurated in 2011. 

Tocharian mummy buried with marijuana hoardPaleorama[es].

Some 800 grams of the psychedelic plant, including seeds, were found at the burial place of a Tocharian man, presumably a shaman, at Yanghai (Uyghuristan), belonging to the Gushi culture and dated to at least 2700 years ago. The plant belongs to a cultivated variety.
Some of the oldest cannabis evidence are also from that area (Pazyrk culture c. 2500 years ago) and also from Nepal (Mustang, similar dates). Later in Southern Central Asia it was used in combination with opium and ephedra, from where soon migrated to South Asia and many other parts of Eurasia.


New device radically reduces costs and time in DNA extractionScience Daily.
Researchers from the University of Washington and NanoFacture Inc. have developed a device, which looks like a kitchen appliance, able to extract DNA from tissues (like saliva or blood) in minutes at low cost and without using the toxic chemicals habitual in the field.
The prototype is designed for four samples but can be scaled for the lab standard of 96 samples at once.


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. Open accessLINK [doi:10.1038/nature11968]


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, respectively6, 7. Although rates of spontaneous variation in DNA methylation and mutation can be decoupled in the laboratory8, 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 known15, 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.

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Posted by on March 16, 2013 in epigenetics, evolution, Genetics, plant genetics


Non-additive genetic models and the problem of stasis (relative stability of the genomes) and missing heritability

A simple and classical approach to genetic understanding of phenotype variability is to assume that allele influence is additive. However this may be just a mirage of imperfect methodology.
In any case the additive model approach has reached a point when it is quite obvious not enough to explain the genetic background of phenotype heritability.
Gibran Hemani et al., An Evolutionary Perspective on Epistasis and the Missing Heritability. PLoS Genetics 2013. Open access → LINK [doi:10.1371/journal.pgen.1003295]

The relative importance between additive and non-additive genetic variance has been widely argued in quantitative genetics. By approaching this question from an evolutionary perspective we show that, while additive variance can be maintained under selection at a low level for some patterns of epistasis, the majority of the genetic variance that will persist is actually non-additive. We propose that one reason that the problem of the “missing heritability” arises is because the additive genetic variation that is estimated to be contributing to the variance of a trait will most likely be an artefact of the non-additive variance that can be maintained over evolutionary time. In addition, it can be shown that even a small reduction in linkage disequilibrium between causal variants and observed SNPs rapidly erodes estimates of epistatic variance, leading to an inflation in the perceived importance of additive effects. We demonstrate that the perception of independent additive effects comprising the majority of the genetic architecture of complex traits is biased upwards and that the search for causal variants in complex traits under selection is potentially underpowered by parameterising for additive effects alone. Given dense SNP panels the detection of causal variants through genome-wide association studies may be improved by searching for epistatic effects explicitly.
It is difficult for me to explain (or even understand well in some aspects) the issues under debate here but some excerpts from the text do ring very true in my mind:
There exists a paradox in evolutionary biology. Despite a near-ubiquitous abundance of genetic variation [1]
traits under selection often evolve more slowly than expected and,
contrary to expectation, genetic variation is maintained under
selection. This problem is known as ‘stasis’ [2], [3], and it is particularly evident in fitness-related traits where the genetic variation tends to be highest [4] yet there is commonly no observed response to selection at all [5][7].
After hundreds of genome-wide association (GWA) studies [11]
a picture is emerging where the total genetic variation explained by
variants that have been individually mapped to complex traits is vastly
lower than the amount of genetic variation expected to exist as
estimated from pedigree-based studies, a phenomenon that has come to be
known as the problem of the ‘missing heritability’ [12].
Again, there are probably numerous contributing factors, and ostensibly
the most parsimonious explanation is that complex traits comprise many
small effects that GWA studies are underpowered to detect [13], [14], but whether this is the complete story deserves exploration.

Beyond the realm of complex trait genetics it appears that epistasis
does appear to be common. For example in molecular studies it is routine
to observe ‘phenotypic rescue’ where the phenotypic effect of a gene
knockout can be masked by a second knockout (e.g. [31]). Another commonly encountered form of epistasis is ‘canalisation’ [32], where phenotypes exhibit robustness to the knockout of one gene, requiring a second knockout to elicit a response (e.g. [33]).
At the macroevolutionary scale, epistasis is also of central
importance, for example it has recently been shown that an advantageous
substitution in one species is often found to be deleterious in others,
thus the substition’s effect on fitness is dependent upon the genetic
background in which it is found [34]
The results suggest that we should expect significant levels of
non-additive variation to be maintained in fitness-related traits.
One of the criticisms seems to suggest that studying homogeneous populations in GWAS is inefficient because linkage disequilibrium (LD) masks the non-additive effect of the alleles, making them appear, erroneously, as additive. 
… it was observed that even with modest reductions in LD between causal
variants and observed SNPs all testing strategies tended to decline in
performance rapidly.
The example of the single locus case, overdominance, is central to processes of heterosis and inbreeding depression [52], [53], and has been identified in molecular studies also [54], [55].
Indeed, heterozygote advantage plays an important role in evolutionary
theory, as it confers segregational load on a population, and this type
of load cannot be purged due to balancing selection, potentially
rendering populations susceptible to accumulating a critical mass of
such polymorphisms [56].

It is important to note that the processes underlying stasis and missing
heritability are unlikely to be caused by any single factor. For
example, a compelling argument is that though most traits exhibit
genetic variation, selection acts upon multidimensional trait space in
which there is no genetic variation [59], and this will hold under an additive model of genetic variation.
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Posted by on March 2, 2013 in Genetics, human genetics


Hominid speciation: sudden or gradual?

It depends apparently: bonobos may have diverged quite suddenly while in other cases, including the Pan-Homo split, the process of speciation appears to have been more gradual.

Thomas Mailund et al., A New Isolation with Migration Model along Complete Genomes Infers Very Different Divergence Processes among Closely Related Great Ape Species. PLoS ONE 2012. Open access LINK [doi:10.1371/journal.pgen.1003125]


We present a hidden Markov model (HMM) for inferring gradual isolation
between two populations during speciation, modelled as a time interval
with restricted gene flow. The HMM describes the history of adjacent
nucleotides in two genomic sequences, such that the nucleotides can be
separated by recombination, can migrate between populations, or can
coalesce at variable time points, all dependent on the parameters of the
model, which are the effective population sizes, splitting times,
recombination rate, and migration rate. We show by extensive simulations
that the HMM can accurately infer all parameters except the
recombination rate, which is biased downwards. Inference is robust to
variation in the mutation rate and the recombination rate over the
sequence and also robust to unknown phase of genomes unless they are
very closely related. We provide a test for whether divergence is
gradual or instantaneous, and we apply the model to three key divergence
processes in great apes: (a) the bonobo and common chimpanzee, (b) the
eastern and western gorilla, and (c) the Sumatran and Bornean
orang-utan. We find that the bonobo and chimpanzee appear to have
undergone a clear split, whereas the divergence processes of the gorilla
and orang-utan species occurred over several hundred thousands years
with gene flow stopping quite recently. We also apply the model to the Homo/Pan speciation event and find that the most likely scenario involves an extended period of gene flow during speciation.


Blood groups A and B inherited from simian ancestors

A new study has found that blood group A and B alleles have been stable (albeit in likely dynamic equilibrium) in the primate family since… always.

Laure Ségurel et al., The ABO blood group is a trans-species polymorphism in primates. PNAS 2012. Pay per view (6 months embargo) ··> LINK [doi:]


The ABO histo-blood group, the critical determinant of transfusion incompatibility, was the first genetic polymorphism discovered in humans. Remarkably, ABO antigens are also polymorphic in many other primates, with the same two amino acid changes responsible for A and B specificity in all species sequenced to date. Whether this recurrence of A and B antigens is the result of an ancient polymorphism maintained across species or due to numerous, more recent instances of convergent evolution has been debated for decades, with a current consensus in support of convergent evolution. We show instead that genetic variation data in humans and gibbons as well as in Old World monkeys are inconsistent with a model of convergent evolution and support the hypothesis of an ancient, multiallelic polymorphism of which some alleles are shared by descent among species. These results demonstrate that the A and B blood groups result from a trans-species polymorphism among distantly related species and has remained under balancing selection for tens of millions of years—to date, the only such example in hominoids and Old World monkeys outside of the major histocompatibility complex.

Razib has some more details on the matter (being PPV, I haven’t read it). Still he wonders what kind of disease or otherwise evolutionary pressure may have been so virulent as to keep the whole order of primates (or at the very least all simians) on our toes all these millions of years.
The answer may well be known already: it seems that type A blood protects against the plague, while type B protects against smallpox, both great historical killers of those without enough defenses. However they may favor other less important health problems like blood clots or cancer, enough to exert a mild pressure in favor of a return to the basic type zero (“O”), which would have evolved by loss of function once and again. 
Whatever the case I find fascinating that these immune mechanisms may be so extremely persistent and I wonder if the bacterian mechanisms they confront may be more generic than just an specific disease.
See also: maps of distribution of major blood types.

Update: a pre-print copy of the paper is available at arXiv.


Convergent evolution towards big brains in humans and dolphins

From Not Exactly Rocket Science (via John Hawks’ Weblog):

Every whale and dolphin evolved from a deer-like animal with slender, hoofed legs,
which lived between 53 and 56 million years ago. Over time, these
ancestral creatures became more streamlined, and their tails widened
into flukes. They lost their hind limbs, and their front ones became
paddles. And they became smarter. Today, whales and dolphins –
collectively known as cetaceans – are among the most intelligent of
mammals, with smarts that rival our own primate relatives.

Now, Shixia Xu from Nanjing Normal University has found that a gene
called ASPM seems to have played an important role in the evolution of
cetacean brains. The gene shows clear signatures of adaptive change at
two points in history, when the brains of some cetaceans ballooned in
size. But ASPM has also been linked to the evolution of bigger brains in
another branch of the mammal family tree – ours. It went through similar bursts of accelerated evolution in the great apes, and especially in our own ancestors after they split away from chimpanzees.

It seems that both primates and cetaceans—the intellectual
heavyweights of the animal world—could owe our bulging brains to changes
in the same gene. “It’s a significant result,” says Michael McGowen,
who studies the genetic evolution of whales at Wayne State University.
“The work on ASPM shows clear evidence of adaptive evolution, and adds
to the growing evidence of convergence between primates and cetaceans
from a molecular perspective.”

… continue reading at Not Exactly Rocket Science

Note: it is one of the microcephalin genes, if you wondered.

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Posted by on September 12, 2012 in dolphin, Genetics, human evolution, mind


ENCODE: from mere protein-coding to true program-like understanding of the human genome

It is in the news these days: an intercontinental army of some 440 researchers have taken decisive steps to truly understand the human genome, our base program, helped by the much lower costs of genome sequencing achieved recently.
One of the most remarkable results is discarding that most of our genome is “junk DNA”. Until recently many though that only some 20% of the genome, the protein-coding segments, were meaningful, while the rest was useless “junk” mysteriously accumulated through the millennia. 
Nature is much more efficient than that, it seems, and the reality is that the remaining 80% of the genome is a maze of switches that actually regulate how cells, and the whole body, are built and maintained. A true biological program encoded in DNA.
The main product of this intercontinental effort is a threaded encyclopedia of the human genome, as well as three (freely accessible) articles in Nature:
In addition to all this you may want to visit the ENCODE site or read this one or this other article at SD, for example.
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Posted by on September 6, 2012 in Genetics, global genetics, human genetics


Adaptionism (humor)

From the often great comic strip (cum video theater) Saturday Morning Breakfast Cereal:

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Posted by on August 24, 2012 in biology, evolution, Genetics, humor


Increased complexity in certain regions sets apart human and chimp brains

Frontal lobe (CC-BY-SA-2.1-jp)
This paper looks like a very important research piece for the understanding of the human mind, of what makes our brains specifically human and ultimately of what makes ourselves what we are.
Genevieve Konopka et al., Human-Specific Transcriptional Networks in the Brain. Neuron 2012. (Freely accessible apparently) ··> LINK [doi:10.1016/j.neuron.2012.05.034]


Understanding human-specific patterns of brain gene expression and
regulation can provide key insights into human brain evolution and
speciation. Here, we use next-generation sequencing, and Illumina and
Affymetrix microarray platforms, to compare the transcriptome of human,
chimpanzee, and macaque telencephalon. Our analysis reveals a
predominance of genes differentially expressed within human frontal lobe
and a striking increase in transcriptional complexity specific to the
human lineage in the frontal lobe. In contrast, caudate nucleus gene
expression is highly conserved. We also identify gene coexpression
signatures related to either neuronal processes or neuropsychiatric
diseases, including a human-specific module with CLOCK as its hub gene and another module enriched for neuronal morphological processes and genes coexpressed with FOXP2,
a gene important for language evolution. These data demonstrate that
transcriptional networks have undergone evolutionary remodeling even
within a given brain region, providing a window through which to view
the foundation of uniquely human cognitive capacities.

Hippocampus (CC-BY-SA-2.1-jp)
For what I could understand, mostly from the press release, the authors unveiled increased complexity of the gene expression modulating three regions of our brains: the frontal cortex, the hippocampus and the striatum.
It is not a mere matter of size but specially one of much increased complexity in the wiring of these three regions what seems to make our brains unique. 
The research also reinforces the apparent importance of the much debated genes CLOCK (affecting circadian rhythms, mood, pregnancy and metabolism), FOXP1 and FOXP2 (related specially with speech), whose connectivity is much increased in humans in comparison with our ape cousins.

Denisovan and Neanderthal proviral DNA

A provirus is a strand of autosomal DNA that was inserted by a virus once upon a time and got lost in our genome as junk DNA, not being anymore active (would it remain active it’d be a retrovirus). Such insertions are thought to be unique phylogenetic events. 
New research has identified a provirus* (HERV-K-Ne1 = HERV-K-De6, inserted in Chromosome 5) shared by Neanderthals and Denisovans but not Homo sapiens. This is consistent with the previous data that placed their autosomal DNA closer to each other than to Homo sapiens.
Lorenzo Agoni et al., Neandertal and Denisovan retroviruses. Current Biology, 2012. Freely accessible (letter with supplementary material) at the time of writing this.
It must be noted however the mitochondrial DNA, inherited by pure matrilineage, is much closer among our species and Neanderthals than either one with Denisovans, what to me suggest that Denisovans are no new species but a hybrid of Neanderthal and Homo erectus. A theory not yet fully testable for lack of DNA from Asian Homo erectus.
Interestingly Denisovans have also several proviruses not found in Neanderthals, what could well support my theory of hybridization. The detected provirus could hence have migrated from Neanderthals to Denisovans in the hybridization episode (along with lots of other autosomal DNA), while the rest could have been retained from the H. erectus ancestors by the maternal line. 
However as the article is both very technical and succinct, I can’t be sure right now of how strongly or weakly can this info support the hybridization model (founded opinions welcome). 
In total the researchers detected three Neanderthal proviruses and 12 Denisovan ones, one of which is shared between both nominal species. It is convenient to remind that while the Denisovan genome was very well preserved and sequenced almost completely, the Neanderthal genome is only known in fragmentary form, amounting to about 60% of the actual genome.