On the bottleneck of Males 8 kya (Karmin et al.)

A paper (A recent bottleneck of Y chromosome diversity coincides with a global change in culture, (2015) Monika Karmin et al. Published in Advance March 13, 2015, doi:10.1101/gr.186684.114 Genome Res. 2015.) suggests that the evolution of farming reduced the number of reproducing males to a minimum, and thus created a bottleneck in Y chromosome diversity as many male lineages became extinct as they could not pass on their genes (and Y chromosomes) to the next generation.

The idea is that as humans became sedentary some 10 kya, some males became dominant and accumulated wealth, power and, as expected, this gave them access to the women and excluded the other less "fit" males. The ratio reported for that period is as many as 17 women reproducing for every one man who passed on his genes.

The paper is paywalled, but the Supplementary Material is free. So I peeked at it and was surprised by the following figure (S4B):

Fig. S4B from Karmin et al..

Yes, All populations (But one) see a dip in the effective population size between 10 and 3 kya., followed by a rebound and growth. The only group to show another trend: Andean natives, whose population just steadily declines from 3 kya onwards.

First let's read the Abstract:

Abstract
It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50–100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192–307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47–52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.

But let's not forget that the analysis is based on saliva swabs taken from extant males around the world and the genetic data was then subjected to statistical processing which yielded an evolution of the reproductive populations both male and female.

In other words we are "guessing" how the diversity of Y chromosomes evolved over time in different regions. It is not like they sampled ancient remains and did a direct measurement. This is again, a conjecture based on statistic inferences.

In other posts I have expressed my doubts regarding these methods. Here I express them again.

The "Andeans" that were surveyed were Colla (or Kolla) who inhabit what is now Bolivia and Peru, and raised llama and alpaca camelids and grew crops of corn, potatoes, peppers, squash, tomatoes, cotton, quinoa among others. The other "Andean" group actually lived in the Chaco savanna region, a flat area that lies to the North of Argentina. They grew squash, melon.

What made these people so different from the rest of humans? An explanation is needed.

Maybe the whole dip is just a statistical artifact.

But assuming it is real. Are we to expect that the development of farming (something so labour intensive) would lead to some males prevailing over others and inseminating all available women?

Can we imagine a primitive farmer society with men gathering on average 17 women each, in harems and, obviously dispossessing the other 16 males of women with which to mate with?

How about a world that just became sedentary, with higher ratios of diseases associated to sedentary life, with naturally weaker males dying in their childhood, or later during their teens and early adulthood in inter-tribal warfare? Women, subjected to plunder and rape by the victors would bear the children of the new dominant groups while the other men became slaves with no reproductive rights...

Are we to imagine that Wichi and Colla in South America were less warlike people? or had some other tendencies?

I don't think so, and propose an alternate explanation (admitting that it is not a statistical artifact). It is very unlikely, but somehow explains the bias against men and the drop of diversity... As I wrote in my post on Neanderthal - Human admixture:

Haldane’s law [2] which states that:
“When in the offspring of two different animal species one sex is absent, rare or sterile, that sex is the heterozygous sex”
Heterozygous sex meaning the offspring with two different sex chromosomes: XY, that is, the male. In plain english Haldane is saying that a male (Neanderthal) and a female (Homo sapiens) would have had more daughters than sons (boys would be rare). These few, if any (absent) boys would be carrying their Neanderthal father’s Y (Neanderthal) chromosome and, they would be very probably sterile and therefore did not have children and could not pass on their Y chromosome to their sons.

In other words, humans and Neanderthals mixed and the male Neanderthals passed on Their Y to boys who were sterile and therefore the Y diversity was reduced (every Neanderthal mating was one less human one)...

What about the Andeans... their slump came later and continued... were there relict Neanderthals in America? By the way, look at the curves of the Central Asians and Africans, they dropped and actually, never recovered while the others did. Would this reflect a later admixture in those locations?

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2015 by Austin Whittall © 

On Mutations, mutation rates and Ust'-Ishim

A week ago I read the Supplementary Information on the 45 ky old Ust'-Ishim gene sequencing and also several posts that dealt with this very interesting paper.

I was intrigued by two points: one was their estimation of human mutation rates and the other was the autosomal "diversity" of modern and ancient humans as shown in SI 12. So I decided to write a post on each of those subjects. Today's post looks into the question of "mutation rates", the diversity issue will be the subject of a future post.

Molecular clocks and mutations

It is no secret that I am very skeptical about molecular clocks which tick with a constant rate and therefore allow us to measure the timing of past events such as splits between species or the dates when a given haplogroup appeared. So please read on with this in mind: I don't trust molecular clocks.

The key issues in today's post are:

1. Mutations in humans take place at different rates. Yes, mtDNA, Y chromosome and autosomal DNA mutate at different rates when compared to each other, and that is ok, and explainable. What I mean by different rates is that when we compare the same kind of genetic material: mtDNA against mtDNA or autosomal DNA against autosomal DNA, in different human samples, the rates are different.
2. Genetic mutations grow at different paces in men and women.
3. The DNA of our closest relative, the chimpanzee mutates at a different rate, when compared to ours.
4. More genetic diversity may not mean "older" populations but simply quicker mutation rates that accumulate in a population of the same age as a less diverse one.
5. The concept of a molecular clock is unsustainable.

The "molecular clock" that is used to estimate past events in human evolution is based on the simple assumption that: mutations take place in our DNA at a certain fixed pace and that by comparing the quantity of mutations by which specimen A and specimen B differ, we can calculate the time that has elapsed since they shared a common ancestor.

Neat. But what exactly does it mean? and even more important: is it really a clock?

First of all, lets see what a mutation is:

We are all familiar DNA and its role in inheritance. DNA is a polymer that is found inside each and every one of our cells, inside the cellular nucleus. It is shaped like two intertwining coils (a "double helix") and these spirals are stabilized by molecules known as "nucleobases" (or "bases" for short) which link the coils together.

One base is attached to one of the coils and another base is attached to the other coil; and both bond together to form a "base pair".

Fortunately these bases come in four kinds: adenine (abbreviated A), cytosine (C), guanine (G) and thymine (T) and they link up in a very simple manner:

A only bonds with T and C only links up to G. So the "steps" of the ladder that joins the two spiral strands is made up of base pairs such as:

....
AT
TA
CG
CG
AT
GC
TA
....

During replication, the DNA strands within the nucleus of the cell, "unwind", unzipping each strand. The exposed bases attract a new pair and form the other complementary spiral. The "unpaired" Adenine will attract thymine and link to it while the guanine will bond to cytosine and so forth. This bonding takes place on each of the unzipped strands, so from one (1) initial DNA molecule, two (2) "identical" copies are obtained.

Copies and errors, causes

Well, not exactly "identical", there are some sequence errors, and this takes place even though cells have proofreading abilities and mismatch repair mechanisms that compare original and copied DNAs.

These errors in the transcription mean that the "daughter" DNAs are not an exact replica of the "mother" DNA. So maybe an AT is lost or replaced by a GC or a duplicate is inserted so TA becomes TA TA...

In other words these are natural spontaneously occuring mutations.

Other external factors known as "mutagens" can interact with the DNA and alter the nucleotide sequence producing mutations:

• High Energy Electromagnetic radiation. For instance X-rays or Ultraviolet light (UV).
• Oxidizing agents (or free-radicals).
• Chemicals, such as alkylating agents, heavy metals, solvents, monomers, agrochemicals.

These factors can disrupt the sequence of a DNA strand resulting in a "new" (mutated) chunk of genetic information, either due to deletion or addition of base pairs.

There is also a process known as "Recombination" by which two DNA molecules merge in certain sections and produce a totally new variety of DNA.

Where (and when) do mutations take place?

Those terrible summer sun-burns that I suffered as a child back in the 70s, and the accumulated doses of UV radiation that my skin has received over the years, may result in a mutation that causes skin cancer (I keep my fingers crossed and visit my dermatologist once a year just in case).

The same could be said about the X-rays that have zapped me at my dentist or during my medical check-ups or the cosmic rays that incessantly criss-cross my body. Some pesticides that I ingested via fruits or cereals, those glasses of red malbec (and its metabolized by-products) or the cigarrettes that I used to smoke are also packed with mutagens... which disrupt my DNA here and there.

But all of these mutations which are taking place in some of the 40 trillion cells that make up my body would only affect me and therefore would not be passed on to future generations unless they took place in certain cells and, during a specific time frame which differs for men and women.

The new DNA information created by mutations would pass on to my progeny only if it mutated inside my "germ cells" (sperm in my case since I am a man or, for women: their ova).

Mutations that are inherited: Meiosis

Normally our cells reproduce by a process known as "Mitosis", and its outcome are two cells, each carrying the same genetic information that the mother cell had, as well as the same number of chromosomes.

We humans are dipolid organisms and as such, our cells carry two homologous copies of each chromosome, one inherited from our mother, the other from our father. Our cells therefore have 23 pairs of chromosomes of which 22 pairs are autosomes, one pair are the sex chromosomes (the X and Y chromosomes, paired XX in women and XY in men ). The grand total is 46 chromosomes per normal human cell

But our "germ cells" are different, they can only carry half of the genetic information of each parent so that the combination of the father's sperm and the mother's ovum with their chromosomes add up to exactly the full number of chromosomes.

This process of germ cell formation is known as "Meiosis", and it takes place differently in males and females:

• Females. Meiosis in females is known as "oogonia", and consists of a series of divisions of the "original" oogonium with the complete set of chromosomes, the outcome is an an ovum with half the quantity of chromosomes.
  Meiosis in females takes place during the formation of the embryo (after the fourth week of pregnancy), as soon as the primordial germ cells migrate to the ovary, and they will lie dormant inside a protective follicle until the woman reaches puberty, when her menstrual cycle begins.
• Males. The process in males is known as "spermatogenesis", and takes place in a continuous manner, after puberty, until death. Meiosis produces spermatozoa in the seminiferous tubes inside the testicles.

Implications

Since male germ cells are produced in a constant manner, the different mutagens that interact with an individual during is whole adult life, (meiosis is a continuous process in men) may cause mutations. Furthermore, males have a very poor DNA repair mechanism, so these mutations are more likely accumulate, without being "fixed", and therefore more likely to get transmitted to their offspring.

The female ova, on the other hand are produced during fetal growth, and are placed in hybernation for many years until the onset of puberty. But despite this long period during which external mutagens could interact with the ova's DNA producing mutations, females have a very efficient repair mechanism for postmeiotic stages which can repair DNA until after fertilization. [3]

This means that sperm accumulate more mutations than ova, and men transmit more mutations to their offspring than women do. This has been corroborated by separate studies both in humans and in chimps:

Chimpanzees, our closest relatives have different mutation rates

Chimps are our closest primate relatives, and a recent paper (Venn et al., 2014) [1] found that "mutation rates and patterns differ between [our] closely related species", Venn reported that male chimpanzees pass on between seven and eight times more mutations to their offspring than do female chimps. This means that roughly 88% of the mutations found in their offspring have a paternal origin and 12% are maternal.

Also, the older the father, the more the mutations in the paternal genes ageing adds "three mutations per year of father's age"[1].

In humans on the other hand "every additional year of father’s age contribut[es] two mutations across the genome and males contribut[e] three to four times as many mutations as females." [1], so males provide between 75 and 80% of the mutations and females 20 - 25%. /p>

This increased mutation contribution by males was reported in a genetic study by Campbell et al., 2012 [7] which found among Hutterite families that 85% of the new mutations were of paternal origin. Which is higher than those mentioned by Venn for humans and very close to those of chimps.

Campbell reported the following figures:

SNV mutation rate: 1.20 × 10^-8, (95% confidence interval 0.89 – 1.43 × 10^-8) mutations per basepair per generation. And 0.96×10^-8 for the most recent generation.

The lower mutation rate for the latest generation was justified by "the relatively young age of the father of the trios analyzed here (21–30 years old at the time of the child’s birth)" [7], meaning that a younger father had accumulated less mutations than an older one.

Calculating Mutation Rate

The mutation rate can be calculated using the following formula:

Mutation Rate = # of mutations observed ⁄ (# of generations x # of base pairs sequenced) [a]

By comparing the discrepancies in the gene sequences of two related individuals separated by a given time span the mutation rate can be calculated (i.e. father - son pairs or comparisons of the DNA between living individuals and that sequenced from his ⁄ her ancestors).

Roach et al., (2010) [8] analyzed the full genome sequence of a family (two children and their parents) and calculated a mutation rate of 1.1 x 10^-8 per position per haploid genome.

But what does this mean? Look at it this way: humans have about 6 x 10⁹ base pairs (six billion), so it is very straightforward to work out the number of mutations that will appear in a child, inherited from its parents. They are (see [a] above) directly proportional to the number of bases, the number of generations - in this case = 1 - and the mutation rate. So, using [a] we can calculate:

# of mutations observed = Mutation Rate x # of generations x # of base pairs

So, replacing the terms with actual numbers:

# of mutations = 1.1 x 10^-8 x 1 x 6 x 10⁹

# of mutations = 66 (the new mutations in a child, compared to its parents).

Comments

Out of these 66 mutations, roughtly 80% (or 53 are parental, the other 13 maternal). Since paternal mutations grow at a rate of 2 per year [1], we can see that the child of an "old" dad aged 45 would receive 2 x (45-20) = 50 "extra" mutations in its genome in comparison to the child of a "young" 20 year old father.

So the baby of "old" dad would have 66 + 50 = 106 mutations while the baby of the "young" dad would have only 66 mutations.

Looking at a society where older parenting prevails (young males are not successful in mating with the women, or they die off before bearing children, or their children die off before reaching maturity) we would find that mutations would have accumulated at 106 mutations⁄generation. While a society where young males exclude older ones from bearing children, the mutations would accumulate at a rate of 60 mutations⁄generation.

After "n" generations the situation would be:

Old men society: n x 106 mutations. Time span: n x 40.
Mutations per year: n x 106 ⁄ n x 40 = 106⁄40 = 2.65

Young men society: n x 60 mutations. Time span: n x 20.
Mutations per year: n x 60 ⁄ n x 20 = 60⁄20 = 3.00

On a "per generation" basis there are 76.7% more mutations in the "old men" society, but on a "per year" basis, the mutation rate is 13.2% higher in the "young men" society.

This should be a word of caution when using "generations" to gauge ancient events. The conclusions will be very different in one case or the other.

The variability of Mutation Rates

The problem is that the mutaton rates are quite "variable". A paper by Wang, J. et al., (2012) [9], sequenced individual sperm cells in a 40 year-old individual. They obtained mutation rates of 2.0 to 3.8 x 10^-8, which, are different from other values measured in other studies:

Hutterites (mentioned above): their "SNV mutation rate [was] 1.20 × 10^-8 (95% confidence interval 0.89-1.43 × 10^-8) mutations per base pair per generation." [7]

Pedigree. Xue et al., (2009) [6] compared the mutations detected in the Y chromosme of two members of the same family separated by a span of 13 generations. They reported that "The mutation rate is ... 1.0 × 10^-9 mutations ⁄ nucleotide ⁄ year (95% CI: 3.0 × 10^-10 – 2.5 × 10^-9), or 3.0 × 10^-8 mutations ⁄ nucleotide ⁄ generation (95% CI: 8.9 × 10^-9 – 7.0 × 10^-8)" [6] .

Just look at Xue et al.'s enormous Confidence Interval: it is almost one order of magnitude, that is the upper limit is nearly 10 times the value of the lower limit! This is like saying that we estimate the weight of the stone to be 10 pounds, with a CI of 3 lb - 25 lb.

The range between the minimum and maximum values of these studies goes from 0.89 to 7 x 10 ^-8 mutations ⁄ base pair ⁄ generation. A big window indeed.

Variability between families

Additional proof of the variability of mutation rates comes from a paper (Conrad et al., 2011) [5] which confirms that there is "considerable variation in mutation rates within and between families". The authors compared female and male germline and non-germline de novo mutation rates and found that "in one family [...] 92% of germline DNMs were from the paternal germline, whereas, in contrast, in the other family, 64% of DNMs were from the maternal germline." [5]

Against the constancy of mutation rates

We could imagine that additional research will refine those values and come up with a more reliable rate, but there is another problem: the mutation rate is not constant. It fluctuates accelerating and slowing down over time.

A paper by Amos W., (2013) points out a that "tendency for Africans to have diverged more from chimpanzees than non-Africans is unexpeced under classical theory." [4] Since we all derived from chimps, and have had the same time to accumulate mutations, why do Africans appear more distinct?

Applying the formula [a] it is quite simple to see that if the number of mutations is higher for Africans, then either the number of generations and ⁄ or the mutation rate must be higher for them than among non-Africans. Amos finds no reason to imagine a shorter generation time in Africa (shorter duration means more generations in a given time span). Clearly something is influencing the mutation rates in Africa.

So for Amos, this implies that the anomaly may be due to two reasons "local effects that vary across the genome due, for example, to natural selection, and genome-wide effects arising from a mutator allele impacting mutation rate or demographic influences that alter generation time." [4], the paper suggests that the mechanism that is acting to distort mutation rates is known as the "heterozygote instability" (HI) hypothesis.

Under the HI hypothesis:

mutation rate increases at and near heterozygous sites where the two homologous chromosomes differ in sequence [...] [4]

This means that "gene conversion events focused on heterozygous sites during meiosis locally increase the mutation rate [and] As humans left Africa they lost variability, which, if HI operates, should have reduced the mutation rate in non-Africans. [4]

In other words, the bottle necks that decimated humans (and also their Neanderthal and Denisovan) predecessors as they moved out of Africa and across Eurasia, led to reduced diversity and this in turn decelerated their mutation rate in comparison to those that remained in the African homeland whose diversity remained higher.

"Under the HI hypothesis, this demographically-induced reduction in heterozygosity should create a parallel reduction in mutation rate such that Africans have diverged more than non-Africans from their common ancestor" [4]

I will go over this in detail in my next post on "African diversity vs. non-African lack of diversity", but focusing on this post's subject, how does this impact on mutation rates?

Simple: mutation rate grow with increasing heterozygosity. Also "When population size is constant, smaller populations will experience lower mutation rates than related larger populations" [4].

Summary on mutation rates

DNA mutates at different rates:

• In male or female germ cells
• In different families
• In less diverse populations vs highly heterozygous populations (HI hypothesis)
• In chimpanzees (vs. humans)
• In older men's sperm vs. younger men's sperm
• In large populations vs. small populations

And as we will see below, ancestral DNA (obtained from the remains of ancient humans) show different rates when compared to the pedigree rates calculated by using sequences of recent modern families.

Ust'-Ishim and its estimates on mutation rates

And now, we get to the paper on the Ust'-Ishim remains (Fu, et al., 2014) [2]. Besides a wealth of data on admixture and mtDNA & Y chromosome haplogroups also deals with mutation rates, and reaches some very interesting conclusions (Below I will refer to the Supplementary Information freely available online):

Autosomal Mutation Rates Estimates

The paper measured how many mutations are "missing" in this 45 ky old individual when compared to contemporary humans. The logic behind this calculation is that we kept on evolving during that period of time and accumulated new mutations (see SI 15). Since the bone was carbon dated (41,410 ± 960 BP or 45,000 cal BP) and the substitutions can be measured, the calculation was relatively simple.

As expected, the DNA of Ust'-Ishim is around 0.6% shorter than the A-Panel (a low-coverage of 24 - 32%) modern humans and 0.35% for B-Panel samples (with a higher coverage of 35 -42%). So the autosomal mutation rates are: "0.80-0.91 × 10^-9 ⁄ bp ⁄year for panel-A and 0.44-0.63 × 10^-9 ⁄ bp ⁄ year for the B-panel." [2]

The authors therefore "estimate a nuclear mutation rate of 0.44 -0.63 × 10^-9 ⁄ site ⁄ year, which is lower than the value that has been widely used in the past (1 × 10^-9)." they do point out that the "lower quality A-panel individuals give significantly different results, indicating that this measure is sensitive to quality differences between the compared genomes" [2]

Indeed "different", the values differ by a factor of 2! Notice that they are also giving their figures in mutations per site per Year, further up, the figures we mentioned were "per Generation". Conversion from one to other depends on the time span assigned to a Generation which can range from 19 to 40 years!

Comparing Ust'-Ishim (ancestral) and Xue's pedigree values [4] there is a two-fold spread between the minimum and maximum values.

• 0.44 - 0.63 x 10^-9 ⁄ bp ⁄ year (Ust'-Ishim)
• 0.30 - 2.50 x 10^-9 ⁄ bp ⁄ year (Xue's data)

Mitochondrial DMA mutation rates

Using the mtDNA (SI 8), Fu et al., (which by the way, the mtDNA "appears to be most closely related to the direct R sub-clades R* (P, B, F, T, J)" [2]), they also estimate a mutation rate of "2.53 × 10^-8 substitutions per site per year (95% HPD: 1.76 -3.23 × 10^-8) for the complete mtDNA" [2]. Notice that it differs from the autosomal mutation rate calculated above by a factor of about 50 corroborating that mtDNA mutates rapidly.

Y-chromosome mutation rate

The team also sequenced Ust'-Ishim's Y chromosome and found that it "clusters with the K(xLT) haplogroup." [2], they estimated its mutation rate as "0.76 × 10^-9 substitutions per site per year (95% HPD: 0.67-0.86 × 10^-9)". Which was higher than the rate reported in the controversial paper by Mendez et al. (2013) which discovered a new Y chromosome lineage (A00) with a Most Recent Common Ancestor (TMRCA) of 338 ky, far older than the oldest anatomically modern human fossils.

Table S9.1, shows that the (TMRCA) for all Y-Chromosomes as 153 ky old (range: 132-175 ky).[2], since the mutation rate used is higher, the TMRCA is much more recent than the figure calculated by Mendez (153 ky vs. 338 ky).

A novel calculation of the mutation rate

Fu et al., devised a new method of calculating the mutation rate "assuming the population size history of the ancient sample is identical to that of present humans prior to the death of the archaic individual" [2] , and estimated a muation rate of 0.43×10^-9 per site per year, with a 95% CI (0.38×10^-9 - 0.49×10^-9).

This value coincides with their estimate based on another method and is much lower than other previous values. The fact that the mutation rate is lower and therefore slower means that more time is necessary to accumulate the mutations that we carry, in other words it suggests an older date for the split between modern and ancient humans.

Another recent paper on Mutation Rates

A few days after Fu's paper, another one (Rieux et al., 2014) [10] was published, it reported an improved calibration of the mtDNA clock, and calculated a TMRC for modern humans as 143 ky (95% CI 112 - 180 ky), which agrees pretty well with Fu's estimate.

They ratified the "acceleration of substitution rates in recent times" (for mtDNA mutation rates) which is explained by the " 'time-dependency of molecular rates' hypothesis, which postulates an acceleration over recent times in coding sequences due to the time needed for selection to purge slightly deleterious mutations" [10].

They used two types of estimations, one based on the dates of the fossil remains of ancient humans (tip-based-estimates) and another calibrated on nodes, which mark peopling events such as the peopling of America, New Zealand, Madagascar, etc. They noticed that:

tip-based rate estimates are slower (by a factor of 0.63-fold) than the ones obtained using internal node calibration by Endicott and Ho (2008) but are faster (by a factor of ~1.5-fold) than previous fossil-calibrated rates
[...]
the variance over individually calibrated substitution rates is 11 times smaller for tips than internal nodes. Moreover, all of the 21 substitution rates estimated from aAMH sequences had overlapping 95% HPD (fig. 3). The situation is strikingly different for node-based calibrations, where substitution rate estimates strongly depended on the demographic episode used for dating, with only four out of ten individually calibrated rates having overlapping HPDs.
These results strongly suggest that tip calibration estimates are far more consistent than internal node-based ones. However, tip-based calibration also point to slower mean substitution rates than those based on internal nodes. Thus, one important question we need to answer is whether tipbased calibrations are affected by some systematic bias that might lead to slow (and homogeneous) substitution rates. [10]

In other words, the "nodes" or estimated dates of demographic events have a larger variance than those of the "tips" (reliably dated fossil remains). The 95% HPD interval obtained for each independent ancient sequence overlapped the others while the "nodes" only overlapped in 40% of the cases. (See their Fig. 3). The ancient remains are therefore more reliable than the estimated dates for peopling events! (something I have written about several times suggesting an ancient peopling of America). Additionally the fossils indicate a slower mutation rate meaning a more ancient date for all events (African - non-African split, Sapiens - Neanderthal split, etc.).

Rieux et al. recognize that carbon dated remains are much more reliable than the estimations of dates regarding peopling events (allow me to quote them extensively) :

the uncertainty around dated nodes is far more complex and multifactorial and is likely to lead to different degrees of reliability associated to each node. First, there is generally considerable uncertainty associated with the age of the colonization⁄migration event including error in the dating of the archaeological, anthropological, and historical evidence. The age of the oldest evidence for human presence is unlikely to coincide exactly with the demographic expansion. Very generally, we would predict to see a delay in the appearance of traces of human presence after the expansion of AMHs into any new area (Signor and Lipps 1982).
[...]
Second, even if a demographic event had been accurately dated, the age of the node in the phylogenetic tree might not coincide with it for a number of reasons (Edwards and Beerli 2000; Ho and Phillips 2009; Balloux 2010; Firth et al. 2010; Crandall et al. 2012). For instance, the phylogenetic node of interest may correspond to the most recent common ancestor (MRCA) of the sampled sequences rather than the split of the population of interest.
[...]
the population might have experienced a reduction in size later on, so that the TMRCA could coincide with this subsequent population bottleneck. We could think of additional scenarios and the situation would become even more complex if we considered a possible effect of natural selection. To summarize, node calibration can be affected bymany sources of error, and it is thus nearly impossible to model the age uncertainty around nodes satisfyingly. [10]

In other words, the nodes will give "later" dates for cases like America, subjected to a drastic bottleneck. Even so, I am quite happy to see the dates that they estimated using ancient genomes gave a much older date for the peopling of America than the usual "orthodox" 13 - 17 ky:

Table 2 in [10]. Coalescence Times for Major Haplogroups Involved in the Colonization/Migration Events Considered.

Yet the authors are aware of their "early" dating and try to explain the "discrepancy" to conform to orthodoxy: "However, in the case of the Canary Islands, Remote Oceania, New Zealand, and the Americas, the estimated coalescence times were systematically older than the archaeological evidence. Potential explanations for such discrepancies include ancestral polymorphism in the founding population or complex demographic histories involving multiples wavesof colonists" [10].

Finally their dating of the Divergence between Humans and Chimpanzees was 4.14 Ma (95% HPD 2.991 - 5.448). Which they admit "... may appear too young when compared with the dates that are generally derived from the fossil record." [10] . The authors attempt to explain this "recent" date as due to (i.e. "...more complex speciation scenarios where an initial split was followed by an extended period of gene flow before the final separation..."). But I do not think that it is due to a flaw in their method, but to the dissimilar mutation rates of humans and chimps, as pointed out by Venn et al., in June 2014, [1]:

Under a model in which the mutation rate increases linearly with parental age, the rate of neutral substitution is the ratio of the average number of mutations inherited per generation to the average parental age. We predict the neutral substitution rate to be ~0.46 × 10^-9 per base pair (bp) per year in chimpanzees, compared to estimates in humans of ~0.51 × 10^-9 bp^-1 year^-1 (9). These results are consistent with near-identical levels of lineage-specific sequence divergence (12) but surprising given the differences in paternal age effect. In the intersection of the autosomal genome accessible in this study and regions where human and chimpanzee genomes can be aligned with high confidence, the rate is slightly lower (0.45 × 10^-9 bp^-1 year^-1) and the level of divergence is 1.2% (13), implying an average time to the most common ancestor of 13 million years, assuming uniformity of the mutation rate over this time (95% ETPI 11 to 17 million years; table S11). [1]

This is in agreement with the estimate of Langergraber et al., (2012) who dated the Pan-Homo divergence to between 6.78 and 13.45 Ma.

An earlier human-chimp split renders useless the calculations that calibrate molecular clocks based on that event. If it took place 13 Ma instead of 6, the clock's ticking rate has to be adjusted and all events derived from such a clock would actually be much older than currently accepted. Including the peopling of America.

More to follow, on the differing diversity of humans Africans and non-Africans

Sources
[1] Oliver Venn, et al., (2014). Strong male bias drives germline mutation in chimpanzees. Science 13 June 2014: Vol. 344 no. 6189 pp. 1272-1275 DOI: 10.1126/science.344.6189.1272
[2] Fu, Q. and many others. (2014). Genome sequence of a 45,000-year-old modern human from western Siberia. Nature, 514, 445-450. doi:10.1038/nature13810
[3] Andrew J. Wyrobek et al., (2007) Assessing Human Germ-Cell Mutagenesis in the Postgenome Era: A Celebration of the Legacy of William Lawson (Bill) Russell. Environ Mol Mutagen. Mar 2007; 48(2): 71–95. doi: 10.1002/em.20284
[4] William Amos, (2013) Variation in Heterozygosity Predicts Variation in Human Substitution Rates between Populations, Individuals and Genomic Regions. April 30, 2013DOI: 10.1371/journal.pone.0063048
[5] Donald F Conrad, et al., (2011). Variation in genome-wide mutation rates within and between human families. Nature Genetics 43, 712–714 (2011) doi:10.1038/ng.862. Published online 12 June 2011
[6] Yali Xue et al., (2009). Human Y Chromosome Base-Substitution Mutation Rate Measured by Direct Sequencing in a Deep-Rooting Pedigree. Curr Biol. Sep 15, 2009; 19(17): 1453–1457. doi: 10.1016/j.cub.2009.07.032
[7] Catarina D Campbell, et al., (2012). Estimating the human mutation rate using autozygosity in a founder population. Nature Genetics 44, 1277–1281 (2012) doi:10.1038/ng.2418
[8] Roach JC, (2010). Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science. 2010 Apr 30;328(5978):636-9. doi: 10.1126/science.1186802. Epub 2010 Mar 10
[9] Wang J, Fan HC, Behr B, Quake SR, (2012). Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm. Cell. 2012 Jul 20;150(2):402-12. doi: 10.1016/j.cell.2012.06.030
[10] Adrien Rieux, et al., (2014). Improved Calibration of the Human Mitochondrial Clock Using Ancient Genomes. Molecular Biology and Evolution, 2014, 2780-2792, DOI: 10.1093/molbev/msu222

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2014 by Austin Whittall © 

Y chromosome Haplogroup R in America

The overlooked lineage

There is a very particular Y chromosome haplogroup in the Americas which is often ignored, overlooked or clumped together with "others" since it is not considered a founding lineage: haplogroup R. with its M173 mutation.

I believe that there are several reasons for this omission, one well founded in common sense, others shielded in political correctness:

• The logical reason is simple: Since modern Eurasian populations are predominantly haplogroup R, the Spaniards and Portuguese, French and British have a high proportion of hg. R in their genes. It was these people who discovered and conquered America so their admixture with the conquered American Native races will surely be reflected in contemporary Native Americans' Y chromosomes by the presence of typically European R haplotypes.
• The politically correct reasons are several: for instance wacko white supremacist claims of European pre-clovis presence in America via a trans-Atlantic Ice Age crossing (Solutrean hypothesis). Then there are some religious beliefs involved (Mormons) with lost tribes reaching America, and things can get even worse: Atlantean migrations... you get it, sci-fi junk. These strange theories are frowned upon by mainstream scholars and even a slight formal support to any of these notions is academically unacceptable. As an example see Stanford and Bradley (2012) who support the trans-Atlantic route [1] and a rebuttal of their theory (Erena et al., 2013) [2].

Then we have the political issues, those involving race, past discrimantion and guilt for the actions of our predecessors regarding their racism and the atrocities that they committed against the natives. It also involves an overly sensitive Native American society, overreaction which is often impeding the course of science and the advancement of mankind's knowledge as a whole. As examples of this I can cite the legal battles at court as allowed by U.S. law (Native American Graves Protection and Repatriation Act - NAGPRA), which have removed from further study ancient remains not even distantly related to contemporary plaintiff tribes.

It is, I believe, for these reasons that any hypothesis that suggests the presence of any kind of Europeans (even the Paleolithic ones) among the ancestors of Native Americans is, to put it mildly, discarded. No wonder the Kennewick man and the Windover Bog remains in Florida did not provide clear evidence of their sexual chromosome haplogroups. I don't believe in conspiracies, but botching up the sequencing twice, especially by a Federal organization of contested remains is indeed rather odd!

But let's get back to our post: we will try to look into this thicket of New World R haplogroup and see what can be made out of it.

Haplogroup R in the World

Officially there are two Y chromosome haplogroups accepted as founding lineages in America: haplogroup Q, which prevails among Amerindians with a 92.9% frequency and a less frequent haplogroup C, which is found at a much lower 7.1% frequency among indigenous American men, mostly in North America, but also with a patchy distribution in South America.

Then we have Haplogroup R which is considered by some to also be another Y chromosome founding Amerindian haplogroups. See, for instance Schurr et al., (2004) who add haplogroups P-M45, F-M89 and R1a1-M17 to hgs. Q and C as founding lineages. [13]

But others such as Zegura et al., (2004) [8] are quite convinced that haplogroup R in Native Americans is of a recent European origin and that it admixed into the local natives during the last 500 years, after the discovery of America in 1492.

This is a reasonable assumption: Hg. R is found among Europeans at very high frequencies. But, it is also found all over the world, so why would it be absent in America?

It is believed to have originated after the OoA (Out of Africa) migration of modern humans some 50 kya, in some part of Western Asia, from where it mutated and spread into Europe, Siberia, India, Eastern Asia, Southern Asia and even Australia. Surprisingly it is also found in Africa, as (according to mainstream science) the outcome of a back-migration from Asia.

Although the presence of hg. R in South eastern Asia and Australia could also be attributed to European colonization (the Spaniards in the Philippines, the French in Indochina, the Dutch in Indonesia, and the British in Australia, etc.), but actually there is no serious academic objections to the notion that these are local Asian haplotypes and not the outcome recent admixture. The table below combines data from three papers to show the frequency of hg. R in certain parts of the Old World and the Americas [14][11][8]:

The table is quite enlightening: the Asian frequencies are relatively low (2.5 to 8.6%), furthermore haplogroup R has not been detected in the highlands or coastal areas of Wests New Guinea and Papua New Guinea, New Britain, Moluccas, Vietnam (surprising since this was actually a French Colony) Taiwan or China.

The American data on the other hand is quite different; the frequencies are much higher among some groups (12.6 to 100%), and lower in others (2.5 to 8.3%), at levels similar to those found in Asians. And, yes, some Amerindians do not carry hg. R: Seminole, Shawnee, Kickapoo, Fox, Omaha, Mixe, Ngobe, Kuna and Emberra. Did they escape this suggested European admixture by some miracle?

This panorama indicates, in my opinion that America has the basic ancient coating of haplogroup R at Asian levels which was later overlain by additional hg. R from the European settlers. There are also some local hotspots with much higher frequencies due to the original peopling and distribution wave of native Americans in the New World and not as we will see below, due to higher admixture with Europeans in those regions. The problem is that mainstream science places all hg. R natives into the "mixed - races" category and dismisses haplogroup R as a founding lineage among Native Americans.

Haplogroup R in America

Haplogroup R is found at very high frequencies in Northern North America and is widely dispersed among most native groups: "In total, 73% percent of the populations analyzed exhibited haplogroup R, which ranges in frequency from 4 to 88%" [12], which is quite significant.

The following map is the one that awoke my interest on haplogroup R among Amerindians, and the reason for it is the very odd distribution gradient of hg. R in North America.

Take a look at the map (and the one below it which compares current population densities and hg. R's frequencies): you would expect a higher frequency of European haplogroup R in the regions where contact took place, that is, within the territories of the European colonies (which basically coincide with those that nowadays have the highest population densities). But the maps show something very different!

Native American frequencies of R haplogroup, From [12]

As you can see the highest frequencies are in the area just south of Hudson Bay in Canada (around lakes Winnipeg and Manitoba), and across N.W. Canada into Alaska. In the U.S., they fall off towards the South West. Mexico in general is a low frequency region with a slight increase among the Maya in Yucatan and the Pima and Seri close to the base of the Californian Peninsula.

The distribution does not coincide with current highs in population density or with those of the past in either Mexico or Canada or the US. So how did this supposedly European haplogroup enter the native genome? Physical proximity with a European for intercourse and baby-making is critical for admixture.

The paper (Malhi et al., 2008) [12] in which this map was published attributes this frequency distribution to : "... the earlier occurrence of European contact in Northeastern North America, which has provided a longer period of time for admixture to occur." [12]. I disagree for several reasons:

1. Hudson Bay and Manitoba of all places, were a zone of pelt trappers not thickly populated regions where Europeans and Natives could have had the chance to admix as for instance in coastal New York state or Maryland.
2. The same can be said about British Columbia and the Northwestern Territories
3. Additionally, long before the founding fathers reached the U.S. during Elizabethan times, Spanish conquistadors had been criss-crossing what is now southwestern US (at that time part of the Spanish Viceroyaty of Nueva España which comprised California, New Mexico, Arizona, Texas, Utah, Nevada and parts of Wyoming, Kansas and Oklahoma) and Mexico (since the early 1500s). These chaps would have definitively left their imprint in the local women... Yet, we can see that this region has an even lower frequency than that of the Canadian wilderness.
4. The whole of Mexico which has a very dense population and a history of admixture (more on this below) of Spaniards with Native Americans and also (but to a lesser extent, African slaves) has a very low frequency of haplogroup R. Why?

The map shows, in my opinion, no correlation whatosever with the European colonies and the quantity of hg. R found in the natives' genomes.

On Mexico, Latin America and Spanish open mindedness

Spaniards have a high frequency of hg. R and were particularly keen on mingling with the locals (natives) and with the African slaves (in Northern South America and Central America mostly), to an even greater degree than the more Puritan New England settlers (which according to Malhi are those who mixed with the natives!).

Admixture was due to a very concrete cause: women did not want to cross the oceans and settle in the New World. The few that did were wives of the Royal government officials. So the only available source of women were the local natives. Initially Spanish colonies were based on exploiting the local natives in mines and smeleters to produce precious metals for export back to the Metropolis. The conquistadors were men whose aim was to make a quick fortune and return home to wife and family. Their relationships in America were basic and obviously had only one outlet: the local women. Only much later would European women migrate to America but again, they would only wed within their social circles.

So quite soon, Spanish American societies had plenty of mixed -race people: Spanish with Indian resulted in Mestizo, Spanish and Mestizo in Castizo, Mestizo and Indian: Coyote, a black and a Spanish woman: Mulato, and so on....

To maintain social order, each group had its privileges and obligations marked out by the Crown's law (for instance Mestizos could not bear arms or have Indians given to them as encomienda -a form of serfdom) [5], these legal inequalities eventually festered into the independence revolutions that began in 1810 and led to the creation of Spanish Americas Republics, ran by Criollos (descendants of Spaniards, but born in America) and Mestizos.

The image below show a Mestizo, the mixture of White European and Native American. According to a Mexican Colonial period painting (1700s).[4] (See more admixture examples, Casta paintings)

Mestizo. Castes in Colonial Latin America

So, why is the prevalence of R haplogroup lower in Mexico and their former Colonial territories in S.W. USA? Do Spaniards have less proportion of haplogroup R than the French (in Canada) or the Britons (in the Eastern Seabord states)?

No they don't. Current Spaniards have between 51 and 85% haplogroup R. [6], similar to the frequencies found among English and French. So this is not the cause of the unequal cline. And we have seen above that there was no reluctance on their part towards mingling with the natives.

What is more, the Spanish colonial system was based on a firm grip over the natives: they replaced the theocratic Aztec, Inca and Maya states with their own bureaucracy (plus the Catholic church), and the lives of the natives remained virtually unchanged (something easy to verify by travelling around rural Latinamerica). Native villages (Pueblos de Indios) in Spanish America would have been very apropriate for admixture, far more better than the nomad camps or N.E. American natives. But the map shows us otherwise...

I believe that the reason for this is that haplogroup R was already present among the natives as a founding clade in America, introgression with Europeans added some percentage points to the mix, and very likely it incorporated new European R haplotypes, but there was a substantial presence of hg. R among North American natives. These appear as we will see below in the joining-network trees as outliers with unique haplotypes not shared with Europeans. The exceptions that confirm the rule.

The issue can be easily settled. An in depth sequencing of native hg. R haplotypes would help distinguish the "American" lines from those haplotypes that are surely "European", however this has not been done. There is a clear preconception - prejudice among scholars that simply ignores the option that hg. R is a founding lineage among Amerindians.

Bias and preconceptions

Since most studies consider haplogroup R as a non-Native American line, it is "often removed from phylogenetic analysis" [10]. As an example I quote a paper (Malhi et al., 2008) which describes the methodology: "All individuals that did not belong to haplogroup Q and C were excluded from the Haplotype data set because these haplotypes are likely the result of non-native admixture" [12]. And that is that; the data that is inconvenient is not even analysed.

In all fairness, some studies have included Amerindian hg. R in their data (to disprove it as a founding lineage) and others have proposed it is a founding lineage, but that was long ago and has not been forwarded lately:

Lell et al., (2002). [9] reported the presence of the R-M173 marker, which indicates haplogroup R1, adding that it was "only found in the M45 Y chromosomes of the eastern Siberians and North and Central American natives and not in those of the Middle Siberians or South Americans". Since M45 is a marker of P haplogroup, and R1 is downstream from P, Lell's comment is correct. Unfortunately his suggestions have been disputed.

For instance [8] assigns a post-1492 origin to 96,2% of the natives belonging to Hg. R. (by the way, R accounted for 13.4% of the total haplogroups). This leaves open the door for the remaining 3.8% as belonging to an ancient non-European R haplotype, but this option is not discussed in the paper.

Network comparisons as the one shown below (Fig. 5 in Zegura et al., 2004) [8] compares Asian, American and European individuals. The paper uses the nomenclature of that time, before marker M343 was discovered and used to identify Hg. R1b, so they refer to SNP P25 to identify R1b (it was used from 2002 to 2004 for this purpose). Since the authors are using a marker close to the root they encompass all of R1b (from the most common European lineages - R1b1a2a - to other Asian ones which are less frequent).

The tree is the following: [8]. It only shows groups that cluster more than two individuals (if it had included those with only one individual, would the picture be different?). Branch length is proportional to the number of one-repeat mutations separating any two haplotypes.

The authors point out that the shared Euro American central node (which includes Sioux, Mixtec, Cheyenne, Wayu, Greek, Italian, Russian, and Briton) has a common haplotype different to the Asian model haplotype in two markers. They also add that "Extensive sharing of haplotypes between Native Americans and Europeans is evident throughout the network".

Based on this and a non published analysis which showed that "five European populations formed a distinct cluster with five of the seven Native American groups. In contrast, none of the four Asian populations were part of the European–Native American cluster" [8], the authors concluded that haplogroup R found in Amerindians was due to European admixture.

Which sounds reasonable but... Looking at the figure, there is a very long exclusively American haplotype on the bottom of the image which has several mutations. Then there are the uniquely American ones on the top (marked with red dots). These are distinct and not "shared" with Europeans. Furthermore, the Euro-Asian group on the right (marked with a blue dot) shows substantial admixture between Asians and Europeans and is also linked to haplotypes shared by Amerindians. This clearly shows an Asian link to America.

The other information that is reported in the paper, (but whose data is not shown) is also curious: it states that 2 out of 5 (or 40%) of the Native American groups do not form a distinct cluster with the European populations. This means that they are "separate" from Europeans...How can that be explained in terms of a uniquely European source for Hg. R? (No wonder the data is not shown).

Finally there is the alleged "modal haplotype" shared bye Europeans and Native Americans mentioned in the paper [8], actually, the following table, from [10] indicates a wide variety of haplotypes and not one of them (they are from Central America and Chibchan natives) belongs to this "modal haplotype" yet all of them are R1b haplotypes. For comparison I added the "modal haplotype" as the first row, in red:

The paper [10] also includes a joining-network for hg. R1b among Mesoamerican natives and finds it similar to that of hg. Q3 (a recognized founding lineage) interestingly it shows "better segregation among male lineages" but the haplotype diversity (which can be seen in the table above) is attributed to "over 500 years of European contact in the region". Interestingly, one population did not have any R1b, the Maléku. (Why? were the Maléku reclusive? their women ugly or unfriendly towards Europeans? or simply because they were a distinct ethnic group that did not have this haplotype) Remember the Seminole mentioned at the beginning of this post? They had no haplogroup R either. How can that be explained in the framework of the Euro-admixture-model?

Another paper [7] also compares haplotypes (and does not including the data either) and finds "exact or near matches between the haplotypes of nonindigenous lineages and those haplotypes of Europeans. Hence, although these men are Aboriginal, some of their genetic ancestry traces back to Europe", once again these "near matches" should be interesting since it is in the differences where we will learn something. Furthermore the paper overlooks something very interesting: 28.3% of the populations sampled belonged to hg. R., the majority were R1b1a2, but 2 individuals out of the 40 belonging to hg. R, were typed as being R1a1a1*. This is an uncommon paragroup identified by the mutations M17 (for R1a1a) and M417 (for R1a1a1), both are very basal and are found in men living in a vast area: Northern India, Slavic countries, Siberia, and, evidently America. This is not the typical R1b Western European haplotype, it is a rare variety.

Of course, the authors [7] do not analyse the R hg. samples at all. They declare it foreign and then focus on the accepted Amerindian lineages (Q and C).

Getting back to network comparisons, Bolnick et al., 2006, [11] find hg. R present in 31.0% of their sample and openly admit that "Haplogroup R-M173 likely represents recent (post-1492) European admixture, as may P-M45*", they point out that the median-joining network (their Fig. 6, which I include below, colored to highlight some points) "shows no clear-cut patterns. Haplotypes in this network do not cluster by population, culture area, language family, or geography. This lack of structure is consistent with the hypothesis that haplogroup R-M173 represents recent (post-1492) European admixture in eastern North America rather than a founding Native American lineage" [11].

Actually the fact that they are not linked to any other variable is similar to that of Hg. C in its pan-global range and may have a similar ancient origin that predates culture or language barriers among Amerindians.

Image caption: (b) Pink circles represent haplotypes shared with Europeans, striped circles represent haplotypes that are one mutational step away from European R-M173 haplotypes, and red circles represent haplotypes not shared with Europeans. TMC, Turtle Mountain Chippewa; WC, Wisconsin Chippewa; Sio, Sisseton/Wahpeton Sioux; CA, Cheyenne/Arapaho; Mic, Micmac; OC, Oklahoma Red Cross Cherokee; SC, Stillwell Cherokee; Chic, Chickasaw; Crk, Creek; Sem, Seminole.

It is clear as the authors point out that the most common American haplotypes are shared with Europeans (pink circles) but there are also those (red circles) that are uniquely American. They are not shared with Europeans and do not conform to geographic restrictions either (see Fig. 6 a in [11]).

The authors support the Euro-admixture theory stating that a total of 62 R haplotypes found in Eastern North America are "rare or absent in Asia" or that "the most common R-M173 haplotype in eastern North America is also the most common R-M173 haplotype in Europe, but this haplotype is rare in Asia (and therefore unlikely to be a founding lineage)" [11]. But this overlooks the devastating effects of Old World disease on the native Americans which may have selected negatively against those Asian-American haplotypes while favoring the Euro-American ones. Not because of the haplotypes themselves, but to other genes received from European fathers.

Sequencing the Y chromosome hg. in remains of Amerindians will also let us glimpse the variety and frequency distribution present among pre-discovery natives. I fortell that we will be surprised by those studies.

We should always remember that we are looking at those who survived and not the millions who perished and took their haplotypes with them to their graves.

The authors dismiss the "14 [haplotypes that] are one mutational step away from known European haplotypes [and the] Five haplotypes [that] are 4–8 mutational steps away from European haplotypes... they probably also stem from recent European admixture: the median-joining network suggests that they derive from separate European haplotypes." [11]. This is because they do not cluster together (maybe they did - pre conquest genocide, evidence erased from current populations).

Yet it is remarkable that 14 haplotypes differ from the purported European sources while 5 are even more mutated still! The reasons for this are not given and no explanation is attempted. For instance: they are older and therefore had more time to diversify; they arrived via Asia, and are different to those that came via Europe.

But, having said all this, the authors are not too emphatic against an Asian origin: "Thus, few, if any, R-M173 haplotypes in eastern North America are likely derived from founding lineages of the Americas." [11], they leave the window open.

Closing comments

Having looked at the frequency distribution map in North America and the academic interpretation of European admixture, I am surprised at how "active" the British and French settlers were in their socializing with the natives. Their degree of admixing with them is well above that of the Spanish in the rest of Latin America (and South Western US) as well as the Portuguese in Brazil.

Which seems highly unlikely due to the nature of the Puritan British in the North which would have precluded such introgression and the well documented Spanish - Native mixing in the South.

Why is this admixture so strong around the Great Lakes and the vast empty forests of Central Canada? Those places are far away from the densely populated regions where introgression would have been easier... something is not right with the orthodox explanation. While the obviously simple explanation is very reasonable: that was where these people carrying hg. R settled after reaching America.

Though R haplotypes detected in the very limited studies conducted so far are "rare" in Asia and "identical" or "near matches" to European ones, there are unique Amerindian haplotypes which are not shared with Europeans. Furhtermore "rare" does not mean absent, and additionally, haplogroups that do not exist in Eastern Siberia are found in America and nobody is concerned about it. Lets use the same scales to measure our theories.

So this makes it probable that R1 reached America via Beringia in the wave that peopled America over 25 kya.

R and Q appeared in a similar region in Central Asia, descended from Hg. P., why would R spread across Siberia eastwards and remain on the brink but not enter America? (yes, there is an explanation, but I do not agree with the Bergingian standstill theory and the isolation of America). Add to this the rare high frequencies of mtDNA haplogroup X which are found precisely among the Northeastern North American natives, where R is preponderant! and it makes you ask: did mtDNA hg. X and Y chromosome R reach America together, carried by the pople who settled N.E. America? Maybe they did.

For those looking for other logical explanations here are some interesting ones:

• Escaped Slaves. An interesting suggestion was put forward by Clyde Winters (2011) [15], and suggests that the high frequency of R-M173 among Seminole and Ojibwa (groups with the highest values for R hg.) is due to admixture, but not with Europeans, instead it was the outcome of intimate contact with African males (escaped slaves). The logic behind the paper is that white Europeans were at war with the natives and would not have mixed with native women, but escaped slaves would have, as they found a safe haven to rebuild their lives.
• Pre Discovery contact. Perhaps the source of European genes were the Portuguese and Galician (Spain) who fished cod during the Middle Ages on the Terranova banks, just off the Eastern Seabord. We can imagine some castaways melting into the local natives and sowing their seed. Another option is the Vikings: they founded a village (L'Anse aux Meadows, Newfoundland) and may have raided and raped their way along the Northeastern shores of America...

Sources

[1] Stanford D. and Bradley B., (2012). Across Atlantic ice: the origin of America's Clovis culture. Berkeley: University of California Press
[2] Metin I. Erena, Robert J. Pattenc, Michael J. O'Briend and David J. Meltzer, (2014). Refuting the technological cornerstone of the Ice-Age Atlantic crossing hypothesis. Journal of Archaeological Science 40 (2013) 2934 - 2941 http://dx.doi.org/10.1016/j.jas.2013.02.031
[3] U. S. Census Bureau Maps of population density
[4] See more Images, Casta paintings, Lasalle University
[5] Norma Angélica Castillo Palma, (2001). Cholula, sociedad mestiza en ciudad india: un análisis de las consecuencias demográficas, económicas y sociales del mestizaje en una ciudad novohispana (1649-1796). Plaza y Valdes
[6] Carlos Flores et al., (2004). Reduced genetic structure of the Iberian peninsula revealed by Y-chromosome analysis: implications for population demography. European Journal of Human Genetics (2004) 12, 855–863. doi:10.1038/sj.ejhg.5201225 Published online 28 July 2004
[7] Matthew C. Dulik, et. al., (2012) Y-chromosome analysis reveals genetic divergence and new founding native lineages in Athapaskan- and Eskimoan-speaking populations. www.pnas.org/cgi/doi/10.1073/pnas.1118760109
[8] Stephen L. Zegura, Tatiana M. Karafet, Lev A. Zhivotovsky, and Michael F. Hammer, (2004). High-Resolution SNPs and Microsatellite Haplotypes Point to a Single, Recent Entry of Native American Y Chromosomes into the Americas. Mol. Biol. Evol. 21(1):164–175. 2004 DOI: 10.1093/molbev/msh009
[9] Jeffrey T. Lell et al., (2002). The Dual Origin and Siberian Affinities of Native American Y Chromosomes. Am. J. Hum. Genet. 70:192–206, 2002
[10] Phillip Edward Melton, (2008). Genetic history and pre-Columbian Diaspora of Chibchan speaking populations: Molecular genetic evidence. Dissertation, Univ. of Kansas.
[11] Deborah A. Bolnick, Daniel I. Bolnick, and David Glenn Smith, (2006). Asymmetric Male and Female Genetic Histories among Native Americans from Eastern North America. Mol. Biol. Evol. 23(11):2161–2174. 2006. doi:10.1093/molbev/msl088
[12] Ripan Singh Malhi, (2008). Distribution of Y Chromosomes Among Native North Americans: A Study of Athapaskan Population History, AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 000:000–000 (2008)
[13] Schurr TG, and Sherry ST, (2004). Mitochondrial DNA and Y chromosome diversity and the peopling of the Americas: evolutionary and demographic evidence. Am J Hum Biol 16:420-39.
[14] Manfred Kayser, et al., (2003). Reduced Y-Chromosome, but Not Mitochondrial DNA, Diversity in Human Populations from West New Guinea, Am J Hum Genet. Feb 2003; 72(2): 281–302. doi: 10.1086/346065
[15] Clyde Winters, (2011). Is Native American R Y-Chromosome of African Origin?. Current Research Journal of Biological Sciences 3(6): 555-558, 2011

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2014 by Austin Whittall © 

Not he usual "Out of Africa" cline

A paper (Hai et al., 2012) [1] analized a very special and unconventional gene, miR-941, it immediately drew my attention because it goes against the usual decreasing gradient of variability from Africa outwards, which shows lower variability in the fringe regions that are further away from our purported Eden in Africa. This post will look into this oddity and its implications.

microRNAs or miRNA

Genes usually are in charge of producing proteins or RNA strands (i.e. tRNA) that in turn interact with gene expression pathways. But this is not the case with micro RNAs (miRNAs) which have very important roles in gene expression. miRNAs are short single-strands of RNA (20 to 24 nucleotides long), hence the name "micro".

The appearance of a new miRNA can impact on the expression of hundreds of genes, so for this reason, the the authors of the paper [1] set out to detect a human-specific miRNA and then tried to figure out its evolution and impact on modern humans. They sought microRNAs (miRNAs) specific to the human genome.

The older (archaic or more ancient) miRNAs tend to have higher expression levels than those that have appeared more recently, and a survey of several human-specific miRNA showed just that: low expression levels, a sure signal that they are quite recent. But there was an exception: miR-941 which was found in the human brain at very high expression levels, higher than other miRNAs found in humans and primates.

miR-941

More interesting was the fact that its expression was absent in macaques and chimpanzees showing that it evolved in the hominid line after we split from the chimps some 6 million years ago (Mya). Its upper limit is given by Denisovans, who do also carried it, and this split took place about 1 Mya. So the miR-941 evolved in our hominin ancestrors between 6 and 1 Mya.

What is exciting is the fact that it interacts with our brains, and the human intellect began to evolve during that time span: the "Human-specific effects of miR-941 regulation are detectable in the brain and affect genes involved in neurotransmitter signalling." [1] it is active in the cerebellum and the prefrontal cortex, which are two processing regions within our brains.

The media hyped up this paper based on its role as "making us human" and its impact on our brain-power, but, as we will see below its role is much deeper than that.

The paper suggests that our extended life span and a higher tendency to developing cancer (compared to chimpanzees and macaques) is probably due to this microRNA. So we should thank miR-941 not only our higher reasoning abilities but also our unusually long life span (yes, cancer is a terrible collateral effect). The authors put it this way:

"It is, therefore, appealing to speculate that emergence of miR-941 enhanced the maintenance of adult stem cell populations, thus supporting longer human lifespan, but rendering human cells more prone to malignant transformation. The role of miR-941 in the regulation of insulin signaling adds support to this notion. The insulin-signaling pathway was consistently implicated in lifespan regulation in many species, including humans. Notably, experimentally verified targets of miR-941 within this pathway include genes directly shown to be involved in lifespan extension in model organisms: IRS1, PPARGC1A and FOXO140 (ref. 40). Furthermore, FOXO1 was linked to extended human longevity." [1]

Not the usual cline though

Unlike many genetic markers which show a high diversity in Africa and then a decreasing gradient as you move away from our purported homeland, miR-941 shows quite a different picture:

Although it is found in all humans, the number of precursor copy-number, or repeats is quite variable: it ranges from 2 to 11 copies. This variaton is linked to geographical location too. Although there is a clear indication that the usual decreasing cline is not present in miR-941, orthodoxy compels the authors to affirm that there is a higher African variability and a West to East cline!:

"The average pre-miR-941 copy number decreased from the west to the east: from eight copies in sub-Saharan Africans to six copies in Eastern Asians. miR-941 precursor copy number variation was also significantly higher in sub-Saharan Africans compared with 'out of Africa' populations, with the exception of Oceanians and native Americans
[modern human carry] 2–11 copies of miR-941 precursor, with an average of 8 copies found in sub-Saharian Africa, an average of 7 copies in Europe, America, Oceania and most of Asia, and an average of 6 copies in East Asia." [1]

Look at the figure below (from [1]) and make up your own mind; it shows miR-941 precursor copy repeats in different populations:

The upper part of the image (c) shows that the variability is highest among South American Karitiana (5 to 9 counts), Papuans and Palestinians (4 to 7) folllowed by San (6 to 9). In other words, it is not higest among Sub-Saharan Aficans!

In the case of the Amerindians, it is a surprising find since they are, according to orthodoxy, supposedly a bottleneck population "lacking the diversity of the Africans" , the other Eurasian people -purported ancestors of the American Natives have less variability than Amerindians.

Part d reflects this, showing the average of each region with the highest count numbers in Oceania, Africa and among Native Americans. All other populations have a lower count.

The Variance (in part e) clearly shows the highest variances in Africans and Native Americans. This does not depict a west - east cline, actually it drops off in the middle and grows again as you move on east.

This is clearly at odds with the accepted notion that diversity drops off with distance to Africa, with the New World populations being the less diverse! The authors actually state this mainstream notion in their abstract: "... shows a trend for decreasing copy-number with migration out of Africa" [1] which is not what the facts in their paper shows. (preconceptions are so hard to erase aren't they?).

So even though the main text shows that diversity drops in Eurasia but increases in Oceania and America the authors overlook it and don't even try to seek an explanation for it.

Speculations and Copy-number variation (CNV)

The paper points avoids controversy and does not analyse the significanse of the different Copy-numbers, it merely points out that a different amount of repeats "is not unexpected, given general instability of genomic regions formed by tandem repeats" [1].

But it is not chance that is at play here but natural selection the authors point out tha when a new miRNA appears (obviously its initial appearance is due to chance), it may wreak havoc in the established network due to negative changes in gene expression. So the forces in natural selection would quickly get rid of it or modify the binding sites that produce negative effects. In the case of miR-941, since it was not eliminated, what changed were its binding sites, which were lost.

So if Amerindians have a higher Copy-number variation (CNV), there must be a selective pressure at work. Actually this is the case:

"The "high-degree of copy-number variation (CNV) ... among contemporary human ethnic populations, suggest[s] a high degree of functional variability even among humans. New cell biological funcions acquired because of the appearance of mR-941, for example, new controls over sonic hedgehog and insulin-signaling pathways (Hu et al., 2012), are likely to be important as CNV-dependent determinants of human-specific adaptations to the environment and to disease." [2]

In other words, CNV is important and should not be overlooked.

It is clear that Amerindians and Papuans have a wide range of CNV than Europeans or Asians, and comparable to those of Africans. Yet they are always depicted a population that originated from a founder effect and later went through a bottle neck which reduced its genetic diversity even further. Why is CNV higher among them?

I am at a loss to explain this, but it the high CNV in Oceanians and American natives is a well known phenomenon, and is an incongruity that is explained away as a sampling bias! [3]:

"higher-frequency CNVs were more common especially in Oceania and the Americas... in contrast with their usual reduced variation, populations from Oceania and the Americas had more CNV loci and more previously unobserved loci than most other populations." [3]

The authors try to explain this anomaly as due to "some bias may exist in CNV detection" and go into an elaborate explanation on sampling. Then they simply ignore this large variability in CNVs compared to the usual Out of Africa cline of decreasing diversity and conclude that: [3]

"despite a difference from SNPs in the frequency spectrum of the copy-number-variants (CNVs) detected - including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas- the global distribution of CNVs largely accords with population analyses for SNP data sets of similar size..." [3]

The image below, from [3] actually shows the opposite (peaks in America, Oceania and the Kalash -from Pakistan):

Since African CNV is low, it shows that the high CNV in the Americas is not due to admixture with Africans brought to the New World as slaves. It is due to another cause.

So why do Papuans and Amerindians have a higer CNV diversity?

CNVs can have a negative effect on health and provoke diseases (these will tend to be selected against as the carriers will have a burden which may impede them from having children). Other CNVs have a positive effect and may protect the carrier against disease and "other copy number variants carried by healthy individuals that seem to have no function might actually be evolutionarily retained in populations if they provide a selective advantage." [5]

Could the American and Oceanian variety in CNVs be due to the forces of natural selection retaining CNVs that have been lost by other populations?

Or did they receive these variants from other archaic populations that lived in these areas and admixed with them, receiving these extra CNVs which conferred them a selective advantage?

If so, then the archaic people were already living in America and Sahul when humans reached those regions.

More on the decreasing diverstity myth

When a population with a given diversity (Population A in the image above; diversity is shown by the different colored circles) splits and a sub-population (Population B) moves away, -shown in stage 1- diversity will decrease. In this case we took B as having the same mix as A, but it could have been different, reducing diversity even further (see Population C for instance). The smaller population is more prone to genetic drift which reduces diversity and will also be less likely to evolve new mutations as its size is smaller. It will also be subject to the risk of extinction or loss due to natural calamities than a larger population spread out over a wider territory. So even if the migrating group grows at the same pace as the original population (stages 2 and 3), the outcome will be a reduced diversity.

The acepted theory suggests that variation within a population is proportional only to n (the effective population size) and μ (the mutation rate) which should be the same across all human groups (is it?). [4] So size influences variation: bigger sizes, more variation. Which makes me ask (as an explanation to the higher CNV observed in the New World and Sahul): Did America and Oceania have a larger population in the past which later became extinct? Well, we know that the Americas suffered a devastating impact after its discovery by Europeans in 1492: its population was decimated and its diversity plummeted. Did something simila happen in Oceania? Probably not, as an Old World population they were well adapted to Old World diseases.

Another factor is that, before mutation-drift equilibrium is reached, the age of a population influences its diversity: older populations accumulate more variations. So could the observed CNV diversity be due to an early peopling of America or Oceania by one of our ancestors (Homo erectus? Neanderthal? Denisovans?). This would extend the timeline well beyond the accepted 50 kya for the OoA event or the 15 kya for the peopling of America and allow for diversity to develop.

And, as a closing grand finale look at these two images from Seielstad et al., (1999) [4], which also depict a close relationship between Africans and Americans instead of the usual "decreasing gradient away from Africa":

Yes, the paper (which looks into Y chromosome STR diversity), dates back to 1999 and its figures are extremely unsual but the paper nevertheless echoes the well known mantra of orthodoxy:

"A recent African origin for all humans is supported by a robust corpus of evidence. This evidence takes three major tracks: (1) increased genetic diversity in Africa versus the rest of the world, (2) phylogenetic analyses placing the deepest branches between African and non-African populations, and (3) indications that the age of the “genetic most recent common ancestor” is very young. The Y chromosome, like mtDNA and the autosomes, appears to support a recent African origin." [4]

Sources

[1] Hai Yang Hu, et al., (2012). Evolution of the human-specific microRNA miR-941. Nature Communications 3, Article number: 1145 doi:10.1038/ncomms2146
[2] Antonio Noronha, Changhai Cui, Robert Adron Harris, John C. Crabbe, editors. (2014). Neurobiology of Alcohol Dependence. Elsevier, May 2, 2014. pp 500
[3] Mattias Jakobsson et al., (2008) Genotype, haplotype and copy-number variation in worldwide human populations. vol. 451 doi:10.1038/nature06742
[4] Mark Seielstad, Endashaw Bekele, Muntaser Ibrahim, Amadou Touré, and Mamadou Traoré, (1999). A View of Modern Human Origins from Y Chromosome Microsatellite Variation. Genome Res. Jun 1999; 9(6): 558–567.
[5] Lobo, I. (2008) Copy number variation and genetic disease. Nature Education 1(1):65

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