Patagonian monsters: May 2015

Saturday, May 30, 2015

Unique Amerindian Genetic Trait

My previous post dealt with the anomalous prevalence of Alzheimer's Disease among American Natives, today's deals with another "unique" Amerindian genetic trait, that extends to what in USA are known as Latinos (people with mixed ancestry that includes Native Americans): one that protects against breast cancer.

Breast Cancer incidence by Race USA. From [1]

The table above clearly shows how American Natives and Latinos have the lowest incidence of Breast Cancer among American women.

The cause according to a paper [2] by Laura Fejerman et al.,(2014) is a mutation in chromosome 6: "Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 5′ of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53–0.67, P=9 × 10−18), originates from Indigenous Americans and is uncorrelated with previously reported risk variants at 6q25."

This mutation is the reason that "Latina women, those with a high proportion of Indigenous American ancestry are at a lower risk of developing breast cancer..." [2].

This mutation must have appeared in America otherwise the purported ancestors of Amerindians (as per the Out of Africa theory) would also carry this variant. By the way, the prevalence of Cancer among Amerindians is almost 1/3 of that found among White American women and half of that found among African American women. The Asian Americans' ratio is also almost twice that of American Natives. (these are supposedly the closest genetic relatives to Amerindians).

Is this also due to a bottleneck? or is did it appear during the "Beringian standstill"?

What does the genome of Neanderthal or Denisova tell us about this mutation? I have tried to find information but have not found anything. It may be a mutation inherited from them. Found only in America.

But what about Papuans, who have a high proportion of Denisovan genes? I found two papers (here) and (here) which inform extremely low levels of cance: roughly 8 to 20 times lower than the ratio among Ameridians"!: from 1958 to 1988, the incidence of breast cancer was betwenn 6.9 and 2.4 per 100,000 women.

Do Papuan women have a genetic mutation that protects them too? or is it just lifestyle? Or are these numbers not adjusted by age?

I found another interesting source (global Cancer atlas) which lists cancer prevalence among all human populations. I selected Breast Cancer Incidence and got this map:

Clearly this differs from the other information: dark blue= EU, Australia, America and NZ, Argentina... countries with a high prevalence of White Europeans that eat beef. And low prevalence in "poor" countries where fatty foods are not so common... Asia, Africa, Bolivia. The quality of the data is also variable, ranging from "A" in the US to "C" in China or "G" in Bolivia (19.2 per 100,000 cases) so it makes me wonder how reliable this information is.

Anway, the intersting point is the mutation in Chromosome 6 found among Native American women.

Sources

[1] Zhang and Olopade in Hereditary Breast Cancer. Edited by Caludine Isaacs, T.Rebbeck. pp.234
[2] Laura Fejerman, et al.,(2014). Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25, Nature Communications 5, Article number: 5260 doi:10.1038/ncomms6260

Tuesday, May 26, 2015

Alzeimer's and Amerindian population

Alzheimer's disease (AD) or senile dementia is a disease that, in a world with an ageing population is growing quickly. A study published in biorxiv.org: Chronological Atlas of Natural Selection in the Human Genome during the Past Half-million Years, (2015) Hang Zhou et al., looked into the roots of this disease.

The study finds that "signals of brain evolution in AMH [Anatomically Modern Humans] are strongly related to Alzheimer’s disease pathways." in other words, the genetic changes that led to our advanced brain, as we evolved into modern H. sapiens, also led to our susceptibility to Alzheimer's.

Humans are the only species known to develop Alzheimer's; (AD) the disease is absent even in our closest living relatives, the chimpanzees.

Another paper by Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. (2013), The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013 Jan;9(1):63-75.e2. doi: 10.1016/j.jalz.2012.11.007., gives us an idea of the prevalence of the disease among modern human populations:

"...metaanalysis to estimate the prevalence and numbers of those affected, aged ≥60 years in 21 Global Burden of Disease regions.
RESULTS:
Age-standardized prevalence for those aged ≥60 years varied in a narrow band, 5%-7% in most world regions, with a higher prevalence in Latin America (8.5%), and a distinctively lower prevalence in the four sub-Saharan African regions (2%-4%). It was estimated that 35.6 million people lived with dementia worldwide in 2010, with numbers expected to almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050. In 2010, 58% of all people with dementia lived in countries with low or middle incomes, with this proportion anticipated to rise to 63% in 2030 and 71% in 2050."

Which is rather surprising, if we suffered a bottleneck when we left Africa (according to the OOA theory), most diversity should be found there, in Africa, and the genes that lead to Alzheimer's should prevail there too... but no, it is lowest in Africa and highest in... America, not in the US where you may expect some other external factor at work, no, it was found to be highest among Latin Americans, a mix that has a very high content of Amerindian genes.

But Zhou et al. find Negative Selection (NS) highest among Africans (YRI) compared to Chinese (CHB) or Europeans (CEU): "Regarding the NS signals, a much higher genomic proportion of NS was observed in YRI (~10%) than in CEU (~2.5%) and CHB (~1.9%). One possible reason is that ancient signals of coalescent compression were eliminated by bottlenecks in nonAfrican populations"... which is at odds with AD being more frequent among the supposedly "youngest" population: American Natives.

They also look into Positive Selection (PS) and conclude: "The enrichment of PS signals in brain function beyond 55kya supports the notion that human brain has experienced rapid evolution before OOA. Surprisingly, the 5 ancient brain signals specific to AMH all seem to play important roles in AD pathogenesis. In fact, AD remains arguably a disease unique to humans, as full pathological evidence of AD, particularly AD-related neurodegeneration, are lacking in great apes29. Emerging evidence indicates that AD vulnerability is strongly associated with hyperconnectivity, augmented synaptic and metabolic activities, as well as functional plasticity30. We speculate that the gain of brain function during AMH emergence might have mainly affected synapse networking and neuroplasticity, and this gain was not without a price: it might have led to an increase in structural instability and regional metabolic burden that resulted in a higher risk for neurodegeneration in the aging brain. For the more recent history, the sudden increase of PS signals in stress response in YRI seems to strongly coincide with the emergence of agriculture..."

Once again, PS shaped our brains but also aided development of AD, and again PS is higher among Africans. But they don't have the highest ratios of AD.

I am not quite sure what to make of this. But clearly Africans have the lowest frequency of AD and Latin Americans have the highest. Why? Did a bottleneck make the Amerindians concentrate all the "bad" genes? Is there some external factor that triggers the disease? Does admixture of Amerindians and European settlers increase the risk of AD? It would be interesting to get some data on other groups: Papuans for instance.

Here we have a factor that sets Latinos apart from the rest of the world.

Thursday, May 21, 2015

As they were found in Africa they are tools...

A paper published in Nature describes the finding of the most ancient stone tools, and informs that they predate the genus "Homo". So it was not old Homo habilis who made the first tools. Instead it was made by some other hominin. The authors propose the name Lomekwian for this pre-Oldovan lithic technology.

Below are some photos, of the tools and the site (yes, like my previous post, this one too was inspired by news that I read today in bbc.com)

Lomekwian tools and the site. From BBC.com

The paper (can be read in full) is: Harmand, S. et al. 3.3 Million-Year-Old Stone Tools from Lomekwi 3, West Turkana, Kenya. Nature, published online May 21, 2015

It is an exciting find, pushing back the origin of tool making to the very first of our kin. But it also makes me wonder about the prejudice in science. Similar stones found in America, at the Calico site would be dismissed as geofacts, made by nature, flash floods knocking stones together in a desert environment. Nobody even suggests such an origin for African stones. After all, oldest hominin fossils come from Africa so any old chipped stone found in the area where these people lived must surely have been made by them.

Below are some stones from Calico (source)

They look man-made don't they? However they are considered as natural.

In America, on the other hand, we all know that Siberians migrated there some 15 kya after spending some time isolated in Beringia so anything found in America that does not resemble a modern Homo sapiens "advanced" tool is not even identified by those looking for stone tools (Mousterian, Acheulean or Oldovan tools are not considered when seeking stone tools in America).

We need scientists with an open mind, seeking the truth, not just seeing what they were taught to see...

On the Antiquity of Dogs

I read a very interesting article in bbc.com today and after reading it, remembered having written a post about the antiquity of dogs and the peopling of America.

In it I questioned the authors point of view and wrote: "In my opinion what is missing in the charts is the growth and transition phases of the "S" curve. Dogs did arrive in the New World, but not 9 kya, they arrived 20 or 30 kya, or probably earlier; they probably even originated there and spread to Asia.".

I am a "dog person" and enjoy their company greatly, and most of all, that of my boxer "daughter" Kika. So when the antiquity of dogs is discussed, I have the gut feeling that dogs and humans have enjoyed quite a long and fruitful relationship, not one just 15 ky old, but something much older, in the tens of thousands of years.

The article I read today in bbc.com (DNA hints at earlier dog evolution By Pallab Ghosh) says: "A genetic study indicates that dogs may have begun to split form wolves 27,000 years ago.". It cites a paper by Skoglund, Ersmark, Palkopoulou and Dalén, which can be read in full, has some very interesting findings:

We find that calibration using the most commonly assumed mutation rate of 1 × 10−8 per generation and a 3-year gray wolf generation time would imply that the Taimyr wolf diverged from the Chinese wolf 10,000–14,000 years ago (Figure 3), which is incompatible with its calibrated direct radiocarbon date of ∼35,000 years BP. Instead, the mutation rate must be substantially slower in order to be compatible with the age of the Taimyr individual, and we find that the Taimyr divergence can be accommodated by a mutation rate of 0.4 × 10−8 per generation (Figure 3). However, it should be noted that this assumes that the Taimyr wolf is directly ancestral to the Chinese gray wolf. If there was structure between the ancestors of the Chinese wolf and the Taimyr wolf, the mutation rate would have to be even slower, and as such a rate of 0.4 × 10−8 per generation is conservative. We emphasize that this mutation rate is for non-CpG sites, since SNPs in CpG dinucleotide context were excluded from the variants called in the present-day genome. Alternatively, our results could indicate that the generation time is longer than 3 years, or some combination of slower mutation rate and a longer generation time. Regardless, this direct evidence suggests a longer timescale of wolf-dog population history and thus implies that the 11,000−16,000 years ago wolf-dog divergence inferred in a previous study [15] should be recalibrated to ∼27,000–40,000 years ago.[1]

So they question the mutation rate (the molecular clock that I have criticised so often) and suggest it should be slower. They also question generation length.

They conclude that dogs and wolves split 27 to 40 kya. That is much older than the mainstream 15 kya.

They add that: "Such an early divergence is consistent with several paleontological reports of dog-like canids up to 36,000 years old, as well as the evidence that domesticated dogs most likely accompanied early colonizers into the Americas".

And that is what I believe and surely we will find more proof of an early presence of dogs in America. By the way, the tree published as part of the paper shows American dogs closer to the root of the tree than other Old World ones...

Sources:

[1] Ancient Wolf Genome Reveals an Early Divergence of Domestic Dog Ancestors and Admixture into High-Latitude Breeds (2015), Pontus Skoglund, Erik Ersmark, Eleftheria Palkopoulou, Love Dalén, Current Biology. DOI: http://dx.doi.org/10.1016/j.cub.2015.04.019

Monday, May 18, 2015

We did mix, repeatedly and persistently with Neandertal and Denisovan relatives

A paper published in Nature today, "The diverse origins of the human gene pool" by Svante Pääbo (Nature Reviews Genetics 16, 313–314 (2015) doi:10.1038/nrg3954) is behind a paywall but is quite intriguing, at least to me: the abstract states that:

Analyses of the genomes of Neanderthals and Denisovans, the closest evolutionary relatives of present-day humans, suggest that our ancestors were part of a web of now-extinct populations linked by limited, but intermittent or sometimes perhaps even persistent, gene flow.

In other words... there was flow between Humans and our other relatives. Furthermore this website gives more details:

Human origins debate: Did diversity evolve exclusively in Africa?
Svante Paabo | May 18, 2015 | Nature
Analyses of the genomes of Neanderthals and Denisovans, the closest evolutionary relatives of present-day humans, suggest that our ancestors were part of a web of now-extinct populations linked by limited, but intermittent or sometimes perhaps even persistent, gene flow.
For decades, paleontologists intensely debated how ‘modern humans’ — that is, the direct ancestors of all humans alive today — originated. One view was that modern humans emerged recently in Africa from which they spread worldwide and replaced all other forms of humans, or ‘hominins’, without mixing with them — a process that ended some 30–40 thousand years ago. Another view favoured regional continuity under which hominins in different parts of the world evolved more or less independently over hundreds of thousands or millions of years into present-day humans, with some gene flow between them. This debate was so intense because it bears on the fundamental question of when and where modern humans originated, but it is also of importance for guiding how we should think about the genetic variation in the current human gene pool — does it all go back to variation that accumulated exclusively in Africa, or does it have deep roots elsewhere as well?

I am dying to read more... but will have to wait for others to disclose more details.

Friday, May 15, 2015

On when Humans and Neanderthals admixed

The journal Nature informs about a DNA analysis done to a jawbone found in a cave in Romania which could indicate a very recent admixture of Neandertal genes in humans:

Quote:

"Qiaomei Fu, a palaeogenomicist at Harvard Medical School in Boston, Massachusetts, told the meeting how she and her colleagues had sequenced DNA from a 40,000-year-old jawbone that represents some of the earliest modern-human remains in Europe. They estimate that 5–11% of the bone's genome is Neanderthal, including large chunks of several chromosomes. (The genetic analysis also shows that the individual was a man). By analysing how lengths of DNA inherited from any one ancestor shorten with each generation, the team estimated that the man had a Neanderthal ancestor in the previous 4–6 generations. (The researchers declined to comment on the work because it has not yet been published in a journal)."

This apparently "questions the idea that humans and Neanderthals interbred only in the Middle East, more than 50,000 years ago.".

It makes sense, if your dad or mom were Neanderthal 50% of your genes would be Neanderthal, if one of your grandparents was a Neandethal, you would have a 25% share of their genes, and if it was your great-grandfather or great grandmother it would drop to 12.5%. So if it is 5 - 11% it sounds reasonable to imagine 4 or 6 generations.

Now if we consider that "All humans who trace their ancestry beyond sub-Saharan Africa carry a sliver of Neanderthal DNA — around 1–4% of their genomes." does this mean that we mated with Neanderthals 6 to 10 generations ago? The maths does not seem correct to me.

This dilution depends on how the mixture took place, it is not so straightforward as the article tries to make it appear. Allow me to explain:

Imagine a population of humans and Neanderthals mix equally, 10 men and 10 women, their children will be 50% human and 50% Neanderthal, if we keep them breeding among themselves and we assume no natural selection favoring any genes, after "n" generations they will still have 50% of each genome, that is, 50, 100, 1,000 or 10,000 years later they will still be 50-50.

However if we allow some additional 100% pure humans to mix with them each generation, this will dilute the Neandertal content and increase the Human proportion. Or, on the other hand, if they mix with pure Neanderthal each generation, the opposite will happen, the Neanderthal genes will increase over the human ones.

Then we mus add natural selection which may select against or for certain genes and alter their prevalence at a quicker or slower rate!

I could simplify and say : if current ratio of 1-4% means they intermingled 50kya. Then 5 -11% means they admixed 100 kya... can you prove me wrong?

I have the feeling that Homo sapiens are older than the currently accepted age, and so are Neanderthals, and that we did admix long before 40 or 50 kya.

We will have to wait for the paper to be published.

Sunday, May 10, 2015

Face Mites and the peopling of America

Microscopic mites live on our bodies and faces. We, as hairy mammals offer an interesting habitat to these eight legged creatures related to spiders, scorpions and ticks (all have eight legs). They have been found on all mammals except the platypus and the echidna, hairy monotremes that lay eggs and live in Australia.

There are two distinct species of mites on our faces, inside the pores of our skin . One is short and chubby and lives inside sebaceous glands associated with vellus hairs, it is the Demodex brevis. The other, longer and slender lives above the sebaceous gland, it is the Demodex folliculorum.

We have quite a few per pore, so this means a lot of mites living on our faces. We pick them up after birth, due to contact with our mothers, and relatives. Towels, pillows, sheets... are all vehicles of transfer for the mites.

But it seems that the D. brevis and the D. folliculorum are not closely related to each other. D. brevis is closer to the dog mite, but (see further down, both may even be closer to the goat mite). We may have picked them up from these animals when we domesticated them, or maybe even earlier, from primates.

A paper published in 2013, [1] by Zhao et al. compared some mtDNA from samples of D. folliculorum from China and Spain, and found that: "The average sequence divergence was 1.24% among the five Chinese isolates, 0.94% between the two geographical isolate groups (China and Spain), and 2.15% between the two facial tissue sources (facial skin and eyelids)" their conclusion: "it appears that subspecies differentiation might not have occurred and that D. folliculorum isolates from the two geographical sources are of the same population. However, population differentiation might be occurring between isolates from facial skin and eyelids."

In other words the D. folliculorum found in Spain and China are virtually identical, there was more diversity between Chinese specimens than between Chinese and Spanish ones... but those found on the face skin differ from those found on the follicles of the eye lashesf!

Another more recent study [2] (Thoemmes et al.) took anothe look at this issue and took samples which allowed them to build the tree shown below:

Demodex tree. From [2]

As can be seen the same individuals also carries different populations of D. brevis!

The paper gives a good reason for a greater diversity between geographic locations: D. brevis is buried deeper inside their hosts and this makes it more difficult for them to "jump" from one host to another. D. folliculorum is more superficial and therefore easier to pass on to another person: "D. brevis can be found more deeply embedded in sebaceous glands below the skin surface, in comparison to D. folliculorum that lives more superficially in the hair follicles. These contrasting habitat preferences may lead to more frequent transmission of D. folliculorum than of D. brevis, thus resulting in greater reproductive isolation and geographic structure in populations." [2]

It is very likely that we have carrid Demodex mites with us since we first appeared in Africa, and we carried them around the world with us. So if the American and Chinese mites are different this means that they have been separated for some time. But if European and Chinese mites are more similar [1], does this mean a later split?

When African mites are sampled (Demodex from African populations), will they appear closer to the tree's root? as the Out of Africa theory proposes? or will they be less diverse?

Thoemmes et al found that D. brevis "exhibited higher genetic diversity, not only between mites from the Americas and those from China [...] but also among mites collected from the same individual human [...]. Sequences of 18S rDNA from different D. brevis samples taken from the same face [...] exhibited more genetic variation [...] than those of D. folliculorum taken from Chinese and North and South Americans ..." [2].

They found that the "The Chinese D. brevis samples [and] samples from the Americas each form monophyletic clades with a relatively deep divergence between them [...] The distance between the two D. brevis clades suggests strong geographic isolation among populations of D. brevis. Based on sequence divergence, these two populations are as different as are many congeneric species and subspecies.".

Interestingly the paper [2] points out that: "Phylogenetic estimates based on 16S rDNA also find that dog-hosted Demodex mites share a recent common ancestor with a human-associated species, though in this case D. folliculorum and D. brevis are both more closely related to goat-associated mites, D. caprae. The known habitat of D. canis is deep within the pores and is most similar to that of D. brevis. It is tempting to posit that D. brevis may have colonized humans from wolves during their domestication but any such assertion would be premature. Until other primate species are sampled, the mystery of whether humans acquired Demodex mites from our ape/hominid ancestors or through other means such as our interactions with domesticated mammal species will remain.".

As there are 5,000 species of mammals and each may host 2 species of Demodex... this means 10,000 possible species of which only 13 have been sampled. Clearly we have a long way to go to be able to use them to define ancient human migrations. But the possibilities are enormous and intriguing.

Sources

[1] Ya-e-Zhao et al., (2013) Discrimination between Demodex folliculorum (Acari: Demodicidae) isolates from China and Spain based on mitochondrial cox1 sequences, Journal Journal of Zhejiang University SCIENCE B Volume 14, Issue 9 , pp 829-836
[2] Thoemmes MS, Fergus DJ, Urban J, Trautwein M, Dunn RR (2014) Ubiquity and Diversity of Human-Associated Demodex Mites. PLoS ONE 9(8): e106265. doi:10.1371/journal.pone.0106265

Friday, May 8, 2015

A Denisovan Bracelet?

A very short and interesting (I hope) post: Denisovan stone bracelet, oldest ever found the article with many photographs says that in the Denisova Cave, in the same level where the Denisovan "pinky" was found, the team led by Dr Derevyanko the delicate remains of the oldest bracelet in the world, and it must have been made 40,000 years ago, by Densiovans. A ring was also found, but no details were given.

the image below is from the article:

"In the same layer, where we found a Denisovan bone, were found interesting things; until then it was believed these the hallmark of the emergence of Homo sapiens,' he said. 'First of all, there were symbolic items, such as jewellery - including the stone bracelet as well as a ring, carved out of marble." said Dr. Derevyanko.

Clearly these Denisovans were no brutes, the skill required to work the green marble (imported from a distant site) is something you'd expect from a modern Homo sapiens.

It makes you wonder about who they were, and what were they like....

Another image, showing a reconstruction:

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