An intro to Y chromosome haplogroups

My last post mentioned the possibility of Denisovans being linked to Haplogroup P of the Y chromosome, and the possible presence of haplogroup P in America. I thought that it would be straightforward to associate Denisovans with haplogroup P. But after giving it some thought, it isn't. So I decided to recap and go back to the basics and try to find out if it is feasible to associate Denisovans with any human Y chromosome haplogroup.

Transmission and Mutations of Chromosome Y

Chromosome Y is inherited in a patrilineal manner. All men carry one chromosome X and one chromosome Y, they inherit the X from their mothers and the Y from their fathers. In human beings, carrying a pair of X and Y means you are a man. If you inherit the X from both parents, you are a woman.

Base Pairs

Like all chromosomes, Y is made up of DNA (Deoxyribonucleic acid) a molecule that is made up of two counter-spiraling helicoids (like a winding circular stairway), both strands are made up of sugar-phosphate and are the backbone onto which four different compounds (bases) attach. These are Adenine (A), Cytosine (C), Guanine (G), and Thymine (T); these are the steps of the stairway. The bases bind in a particular way, A with T and G with C.

DNA carries the instructions that the cells can read and use it as a template to build proteins.

The bases are laid down in a certain sequence along the spirals, for instance one strand could have: A T G C C T A G T... and the opposing one would have the complementary bases (a T for every A, a C for each G, and viceversa): T A C G G A T C A...

Each pair of linked bases (the rungs of the stairway) is a base pair, for instance A—T. There are 60 to 300 million base pairs in each of our 46 chromosomes, a total of around 3 billion of them in our genome.

Chromosome Y is the smallest in terms of base pairs: roughly 60 million on average.

Genes

Genes are a specific sequence of aligned base pairs in one chromosome. They are the basic unit of heredity. A gene has the codes required to produce special molecules known as RNA or specific proteins.

When cells replicate, or in the case of our sexual gametes (ovarian eggs and sperm), the chromosomes undergo a process of splitting and the DNA strands unwind and replicate. With 3 billion base pairs, copying the new strands can lead to alterations in the base pairs: mutations.

Some base pairs are lost (deletions) others are copied twice (duplications). This alters the blueprint and may have an impact on how the gene that contains these mutations functions. Mutations can be negative (deleterious), neutral, or even positive. As we will see below, mutations in chromosome Y are problematic, as they accumulate.

Hominin Evolution

Our closest primate relative is the common ancestor that we share with chimpanzees, who lived between 6 and 8 million years ago.

This distant ancestor evolved, through a series of mutations into our homo ancestors: Homo habilis and Homo erectus, and others, reaching the common ancestor of Neanderthals, Denisovans, and Homo sapiens.

The original male hominins living 3 or 4 million years ago, carried certain base pair sequences in their Y chromosomes. We can imagine a small population with a few hundred males sharing identical base pairs (this is of course an over simpification, they differed). These "men" then passed their Y chromosomes with these same sequences to their sons. Some of them probably died in their childhood and did not mate, others only had daughters, so their Y chromosomes were lost, only those who had sons passed them on to the next generation.

Mutations

Each generation went through the same process, but the sequences that were passed on, changed over time as chance and external factoes introduced random mutations in the base pairs of the DNA strands of the Y chromosome.

Below are some of the factors that cause mutations:

• Chance, random mutations.
• Age of conception, those men who reproduce later will have more male germ-cell divisions, and each division entails the risk of a failed copy in the sequence. Formation of sperm (or spermatogenesis) implies constant cellular division over a man's lifespan. Female oocytes that result in eggs are all produced at birth, in one go.
• Methylation, the addition of a methyl group (—CH₃) to the DNA strand due to epigenetic (lifestyle or external) factors such as stress, famine, or toxins (alcohol, chemicals, smoking).
• Oxidative stress. Sperm are also modified by inflammation, heat, radiation (cosmic rays) which can produce free radicals which are oxidants and degrade the DNA.
• Inadequate repair systems, although the Y chromosome has limited repair mechanisms as it is mostly non-recombining (it has no partner like the other non-sexual chromosomes and does not recombine with the X chromosome). It has limited ability to fix glitches due to its high content of repeat sequences called palindromes.

Unlike other chromosomes, mutations can't be purged in Y chromosomes, so if they are harmful, they will accumulate and lead to genetic malfunction (sterility, illness, death, stillborn boys, and miscarriages). The chromosome will not work as expected. Mutations can reverse, undoing the original variation, but it is an unusual event.

The hominins evolved, but the basic structure of their Y chromosomes was similar, only the accumulated mutations, those that had allowed viable offspring survived, the others vanished as those who carried them died.

The whole genome is subjected to mutations, the X chromosome, and the other chromosomes, and natural selection acts, promoting the survival of the mutations that provide an advantage to those carrying them. It is possible that certain Y chromosomes, even though they were fit and possibly provided survival benefits, were eclipsed by deleterious mutations in other chromosomes. This led to the loss of many Y chromosome variants that had evolved over millennia.

The image Below shows an extremely oversimplified version of a Y chromosome. The original, ancestral version is (1) it has 50 million base pairs (not shown), but one mutated, say an A for a T (shown with the red band). It survives in the following generation and after many generations during which othe over the years, and today, when we look at the global population and sample the men, we find the variants marked (2) to (8), each one carries the original "red" mutation but have added others, each identified with a different color (blue, black, orange, green, violet, and gray).

Y Chromosome markers explained. Austin Whittall ©2026

Haplogroups

Here is where modern geneticists and anthropologists use their computer software tools, algorithms, and theory to build phylogenetic trees. They choose certain base pair mutations known as SNPs as "markers" that define "haplogroups" that split populations into branches from a main trunk (the basal one). Assuming that there are no back-mutations, and that repeat mutations are extremely uncommon, they propose that each marker (a mutation at a given base pair) that is fixed in a given population arose in a sequential manner.

In the example shown above, the phylogenetic tree would be the one shown below, assuming that mutations accumulate and don't reverse:

Caveats

We could argue that (8) resulted from (4) that lost its "blue" mutation, but as mentioned further up, orthodoxy considers that back mutations are rare so they ignore them. Problems also arise when we ask which mutation came first, (2), (7), or (8) they are all just one mutation away from the ancestral root.

In the real world, this is far more complicated, especially when we sequence the Y-chromosome of Neanderthals and Denisovans, which have degraded, decayed, and are incomplete. The strands of DNA of ancient remains are full of voids, and bases that have switched, or flipped. Comparing them with modern strands is done with software that "matches" them and points out the differences.

Toomas Kivisild (2017) highlights the complexity of analyzing haplogroups in ancient Y-chromosome samples: "it can be challenging to distinguish true mutations from those induced by damage, particularly in case of C to T and G to A substitutions", contamination is another factor, and the errors caused by low quality readings caused by "coverage" (how many sites were measured in a sample for comparison with a reference genome) and "sequencing depth" (how many reads covered the sample). All of them can lead to incorrect branch lengths, tree inferences, and dating.

SNPs

And mutations can appear in markers leading to mistaken identifications, like the ones reported by A.T. Fernandes, R. Goncalves, and A. Brehm (2004), in the Azores, where "It was found that some individuals share the same haplotype but belong to different Y-chromosome haplogroup suggesting that SNP mutations may occur frequently." SNPs are Single Nucleotide Polymorphisms (a switch in one base, like an A for a T). This paper notes that "The human Y-chromosome haplogroups are characterized by several mutations according to the phylogeny and nomenclature proposed by the Y-chromosome Consortium. Haplogroups are considered to be stable due to the very low mutation rate of most binary markers (SNPs), around 10⁻⁹ per base per generation, showing evidence of recurrent mutation at only 6 of 240 SNPs." This study involved 240 unrelated men and found "three individuals that share an haplotype with a double duplication suggest[ing] that a recurrent mutation occurred in SNP M78 because the duplication event is rare and it is unlikely to occur twice. For the individuals sharing the same haplotype but belonging to different haplogroups two explanations can be possible: recurrent mutations in several SNP namely in M78 and M81 (E3b1/E3b2) and M172 (J/J*) or several STR mutations may have occurred." So much for haplogroups and the assumptions that they are based on! 6 in 240 may seem a low frequency but it is high, 2.5%.

STR, mentioned above is a Short Tandem Repea, a snip of 2 to 6 base pairs long that is repeated two or more times in a location along the DNA strand.

The Branches of the Haplogroup tree

Another factor to consider when looking at ancient and modern DNA is that a man who died 50,000 years ago shows us a picture of a lineage that stopped accumulating mutations then. During the following 50,000 years all other lineages continued adding mutations to their DNA strands at a rate of 10^-9 per base per generation (I am using the SNP haplogroup marker value given above). So assuming generations of 25 years, in 50 ky, there are 2000 generatons, and with 50 million base pairs in a Y chromosome, we can calculate 50 x 10⁶ x 2 x 10³ x 10^-9 = 100 mutations.

When we look at our last shared common ancestor with the Denisovan group who lived ~550,000 years ago, if we assume no mixing with these people since then. After 500 ky, when we met them again in Asia during the Out of Africa migration, each branch, ours, and theirs would have accumulated an average of 1000 mutations (1000 in 50 million base pairs is a very low proportion: 0.002%). With Neanderthals from who we split later, around 350 kya, and met during our first Out of Africa 150 kya, only 400 mutations would have accumulated during the 200 ky we remained apart.

Intra Homo sapiens comparisons like the ones that compare a modern Chinese or a Native American from the Amazon, with an African San, are comparing lineages that have accumulated mutations since they split, probably 60 ky (Chinese and Amerindian) ago from the African line, accumulating mutations separately since then ~120 mutations in each line. And Native Americans with a 30 ky split from Chinese would have added 60 mutations.

Branch Shortening

Finally, and this will be the subject of my next post, mutations do not accumulate at the same rate. Africans have "shorter branches" on the phylogenetic trees. A paper by Petr et al, (2020) using data from an ancient man found in Siberia, Ust’-Ishim, 45,000 years old and modern humans noticed that the number of mutations from the root of each "branche" that leads to Africans and Non-Africans differed, implying different mutation rates (or, in my opinion, incorrect dating of the root, or fork): "Importantly, we discovered that the branch-lengths in Africans are as much as 13% shorter compared to non-Africans, which is consistent with significant branch length variability discovered in previous studies and suggested to be a result of various demographic and selection processes. Notice how they attempt to explain the issue away with "various" processes.

Further reading. Though old and dated, it is short, clear, and comprehenisive. Mark A. Jobling and Chris Tyler-Smith, (2003). The human Y Chromosome an evolutionary marker comes of age, Nat Rev Genet. 2003 Aug;4(8):598-612. doi: 10.1038/nrg1124.

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2026 by Austin Whittall © 

On the diversity of Native American genes

Native Americans are described as the least diverse human beings in the world, bottlenecks along the way depleted variation in their genetic stock, and the small founding population that reached America carried a tiny part of the originally diverse set of genes that they started out with.

However, it seems that there were different waves that reached America, and each one carried diversity, the Amerindians had plenty of varibility but this vanished when the Europeans reached America in 1492.

Eduardo Tarazona-Santos, Denise R. Carvalho-Silva, et al., (2001) in Genetic Differentiation in South Amerindians Is Related to Environmental and Cultural Diversity: Evidence from the Y Chromosome. AJHG, Vol 68:6, June 2001, Pages 1485-1496, https://doi.org/10.1086/320601, argues that it did not cause much difference, that diversity was lost in the distant past, not during European discovery and conquest:

They admit that the population reduction was more severe in Eastern South America than in the Andean region, yet argue that the reduced diversity was not caused by contact with Europeans, instead they suggest that "it has been shown that reduction of gene diversity (i.e., in average expected heterozygosity) began several generations later (Maruyama and Fuerst 1985; Cornuet and Luikart 1996). Therefore, the recent demographic depletion undergone by Amerindian populations 20–25 generations ago could not account for the differences in gene diversity evidenced in the present study, which are more likely to be related to more-ancient (i.e., pre-Columbian) demographic events."

I disagree. The current distribution of natives was also impacted by the European conquest, populations were displaced in the Andean region, from rural areas to cities, from farms to mines, from their homeland to "reducciones" (Spanish word for subduing by force and concentrating in one spot, for easier control an domination), some were over 1,600 km (1,000 mi) from the natives' original homeland, like the Quilmes people, who walked from the Andean foothills in Tucumán to what is now a suburb of Buenos Aires, named after them, Quilmes. See the image (the map is from my website -in Spanish- on Argentina's Ruta 40 highway).

Even the Incas moved people from one part of their empire to another, to settle the newly dominated regions (Mapuches in Chile received an influx of Andean settlers, also the Chachapoyas.) This altered the original genetic patterns and still distorts modern samplings.

Further proof on the drastic decline of Native American populations can be found in Arnaiz-Villena et al., (2025): "After Columbus’s arrival in 1492 AD, the Amerindian population from Alaska to South America (about 80 million) was drastically reduced by 1552 AD (8 million) because of new European-borne diseases (mainly influenza, smallpox, and measles) and war. This drastic population reduction likely caused a genetic bottleneck, which explains why modern Amerindian HLA profiles do not always follow strict geographic patterns. The loss of genetic diversity may be attributed to the selective survival of certain alleles in populations able to present peptides derived from newly introduced pathogens."

The interesting note is the natural selection effect, as the natives died out but some adapted to the new environment, and this promoted the selection of certain genes, resistant to the new diseases, starvation, and exertion of forced work for the conquerors. The real survival of the fittest. 72 million people out of 80 million died, 90% of them! A gigantic loss of genetic diversity.

A similar argument is put forward by Michael H. Crawford (1998) in his work "The Origins of Native Americans: Evidence from Anthropological Genetics" (Cambridge: Cambridge University Press, 49–51, 260–261), quoted below:

"The Conquest and its sequelae squeezed the entire Amerindian population through a genetic bottleneck. The reduction of Amerindian gene pools to from 1/3 to 1/25 of their previous sizes implies a considerable loss of genetic variabilty in New World populations. Who survived the epidemics? It is highly unlikely that survivorship was genetically random."

He then makes the point that those who survived didn't do so by chance, but by natural selection of fitter traits:

"If Amerindians of today are different from their pre-Conquest ancestors with respect to many genetic systems, most likely those genetic traits that confered some selective advantage under the conditions of the Conquest are more numerous among contemporary Amerindians. Thus, the present gene-frequency distributions of Amerindian populations may be distorted by a combination of effects stemming from genetic bottlenecks and natural selection."

An additional factor mentioned by Crawford is the inflow of African slaves and Europeans: "In addition, the gene frequencies of the native populations were further modified by the massive gene flow or admixture with Europeans and Africans, thus possibly obscuring the pre-Conquest patterns. As a result, great care should be exercised in the interpretation of sophisticated multivariate analyses of gene-frequency distributions among New World populations based upon samples collected by various researchers utilizing a diversity of sampling techniques."

Crawford then asks why were Amerindians more susceptible to the diseases brought by the Europeans. In fact, these diseases were also lethal in the Old World, and the African ones, like Yellow fever also wiped out Europans, just as it killed the Native Americans.

He suggestst that "...the death toll from measles was no different than what was observed in European populations that had not been repeatedly exposed to the same disease.... In Europe, epidemics caused by smallpox, yellow fever, and influenza were extremely severe with high mortality. The mortality was somewhat higher in the New World because the disease effects were further exacerbated by starvation, slavery and physical exhaustion. Thus, it has been argued that Amerindians did not have any special sensitivity or susceptibility to imported Old World diseases." This is a novel idea for me, as I had imagined that in Europe and Asia, perhaps those equipped with a fine-tuned immune system, inherited from those who survived epidemics, and through epigenetic changes, created a population that was less susceptible to these diseases. It seems that the situation is different.

So, nowadays, when we look at the genes of "Native Americans" we are looking at what was left of the original diversity, distorted by natural selection over the 433 years elapsed since European discovery, and also, certain admixture of European, African, and also, Asian genes.

A study (Jorge Lindo et al., (2018). Patterns of Genetic Coding Variation in a Native American Population before and after European Contact. The American Journal of Human Genetics, Vol 102:5, 3 May 2018, pp 806-815. https://doi.org/10.1016/j.ajhg.2018.03.008) took a look at current Amerindian genes and the ancestral genetics (from samples taken from pre-contact skeletal remains) belonging to a group of natives, the Coast Tsimshian people living in Prince Rupert Harbour, British Columbia, Canada.

These people have lived there at least for the past 6,000 years and suffered a drastic drop in population after contact with the Europeans which in this part of America was later than in others. In the 1800s they were struck by smallpox epidemics and roughly 175 years ago their population declined by 57%. Then they admixed with people who were not Tsimshian, mainly natives of other groups, and Europeans.

The authors noted that diversity (genetic variation) is the outcome of mutation, recombination, migration, genetic drift, and natural selection, all of these factors played a role among these people.

They found that the ancient natives, compared to the modern ones, had "higher levels of mean observed heterozygosity within coding regions (mean heterozygosity across modern 1.230 × 10⁻⁴ versus ancient 4.935 × 10⁻⁴ individuals)." This is a fourfold difference.

Unexpectedly, the authors expected genetic drift to increase the frequency of certain alleles. The genetic drift would be a consequence of the collapse and slow recovery. However, they found that this didn't happen. They attributed this to the "relatively short evolutionary timescale within which these events occurred; and, second, the recent admixture with both indigenous and non-indigenous populations, which may have increased genetic diversity and countered the deleterious effects of reduced population size"

Another study by O'Fallon BD and Fehren-Schmitz L., (2011) (Native Americans experienced a strong population bottleneck coincident with European contact. Proc Natl Acad Sci USA. 2011 Dec 20;108(51):20444-8. doi: 10.1073/pnas.1112563108. Epub 2011 Dec 5. PMID: 22143784; PMCID: PMC3251087) looked into the effects of European contact: "We find that indigenous Americans experienced a significant contraction in population size some 500 years before the present (ypb), during which female effective size was reduced by ∼50%, thus suggesting that the impact of European colonization was both widespread and severe... the scale of the contraction suggests that the depopulation was not localized to particular regions or communities, and instead, was likely to have been widespread or to have had an especially severe impact on the most populous regions."

Comments

For all of these reasons I am always skeptical on genetic conclusions that are based on admixed, heavily diluted, Native American genes such as those using data coming from CLM: Colombians from Medellín, Colombia, PUR: Puerto Ricans from Puerto Rico PEL: Peruvians from Lima, Peru, or MXL: Mexican Ancestry from Los Angeles, California.

And when a paper uses DNA collected from an Amazonian tribe, the data is usually considered inadequate due to genetic drift and founder effects!

Sampling of ancient, and therefore "pure" Native American genes could provide a real, clear view of the rich diversity lost after 1492.

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2026 ny Austin Whittall © 

Long strands of Denisovan and Neanderthal DNA in Melanesians

Most of us, non-Africans, carry tiny snippets of Neanderthal DNA inside of us, as part of our genome. This is because our ancestors had sex with Neanderthals as they moved across Eurasia, the children born from this admixture carried both Homo sapiens and Neanderthal DNA. Selection weeded out the nasty genes and dilution after countless generations of intra-human breeding watered down the Neanderthal DNA in our genomes, but we still carry roughly 1 to 3% of their DNA in us.

Humans also interbred with the mysterious Denisovans (in Asia), and Melanesians carry roughly 3 to 5% Denisovan DNA with them.

A paper by Ping Hsun Hsieh et al. published today, (Adaptive archaic introgression of copy number variants and the discovery of previously unknown human genes Science - 18 Oct 2019 Vol. 366, Issue 6463, eaax2083 DOI: 10.1126/science.aax2083) took a closer look at this admixture in Melanesians.

We usually carry small snippets of archaic DNA, moswt of these are merely single nucleotide changes, which is a switch in a "letter" of our genetic code, where one molecule (nucleotides are molecules that contain a phosphate group, a sugar group and a nitrogen base) changes for another, for instance an adenine nucleotide (A) changes for a thymine nucleotide (T) altering the genetic sequence.

These single nucleotide changes don't have much of an evolutionary impact, they are therefore immune to selection.

This paper looked for more significant changes: deletions and duplications, formally known as "Copy Number Variants" or CNVs.

And they found that Melanesians carry long strands of archaic DNA in their genes.

The images below are from the paper:

Deletions are parts of a DNA molecule that have been lost during replication. In general deletions are more deleterious than duplications.

Duplications are sections of DNA that are duplicated, as if they were copied and pasted. They are four times more common than deletions. They can be pasted adjacent to the original chunk, and this is known as "tandem duplication" -which are quite rare in humans- or somewhere else ("displaced duplication").

A duplicated section of DNA will of course be passed on to the descent of the mutant carrying it, and will be subjected to the forces of natural selection. If the mutation is beneficial, it will be conserved, but if it alters the metabolism of the person carrying it, selection will weed it out (the person may die or not have viable offspring).

This paper reported 37 CNVs in Melanesians, of which 19 came from Neanderthals and Denisovans. For instance two large chunks of archaich DNA: in chromosome 8, which came from Neanderthals, and in chromosome 16, inherited from Denisovans.

• Chr. 8: Neanderthal with a duplication (38,000 base pairs -bp- long, carried by 44% of Melanesians), and a deletion (6,000 bp long.
• Chr. 16: Denisovan, with two duplications. The first is 380,000 bp long and is found in 79% of the Melanesians that were sampled.

As a point of interest, the first Denisovan duplication lies next to DNA sequences linked to autism (Chromosome 16p11.2 critical region, are associated to roughly 1% of human autism cases).

Also, related to autism, is the region in chromosome 8 (8p21.3) affected by the Neanderthal CNVs. (see more).

The fact that these CNVs have survived tens of thousands of years means that they have contributed some positive trait, that helped those carrying it survive beter than those lacking it. Selective pressure therefore retained these changes as they provided an advantage to the "mutants".

As the paper is behind a paywall I have not been able to read the particulars, but I wonder why do Melanesians carry such large snippets of archaic DNA? Do we all carry long snippets of Neanderthal DNA and it hasn't yet been detected in Eurasians because nobody has looked for it or, on the other hand we don't carry any?

Did Melanesia have specific conditions that favored keeping these duplications while the rest of the world didn't? (certain diseases for instance which can be averted thanks to these CNVs).

The medical significance of these mutations will have to be investigated.

One of the images from the paper suggest that these particular mutations are very rare among non-Melanesians:

The CNVs had first been studied in a paper Global diversity, population stratification, and selection of human copy-number variation, by Peter H. Sudmant et al., (2015) published in Science 11 Sep 2015: Vol. 349, Issue 6253, aab3761 DOI: 10.1126/science.aab3761. It too noticed the high level of Denisovan CNVs, in Melanesians, but not in Australian Aboriginals. They calculated its origin 440 kya among the Denisovans. They mention a chr 16 duplicaton:

"a duplication polymorphism restricted to modern Oceanic populations yet also present in the genome of the archaic Denisova hominin. This 225–kilo–base pair (kbp) duplication includes two microRNA genes and is almost fixed among human Papuan-Bougainville genomes".

This paper (Sudmat el al.,) also studied CNVs among modern humans and were surprised to find that when comparing the difference between Africans and non-Africans regarding deletions and duplications using a parameter they named "Deletion load", "... Africans exhibited an apparent higher deletion load than non-African populations ... Duplications showed no such effect."

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2019 by Austin Whittall © 

On the genes that regulate teeth, archaic hominins and Africans

A paragraph in this paper: Neanderthal and Denisova tooth protein variants in present-day humans) by Clément Zanolli , Mathilde Hourset, Rémi Esclassan, Catherine Mollereau (Published: September 13, 2017https://doi.org/10.1371/journal.pone.0183802) caught my eye. It pointed out an anomaly: Africans sharing a trait with Neanderthals and Denisovans!

This is what it says:

"The finding in living Africans of rare derived polymorphisms that were present in Neanderthals (Fig 2: ENAM G389S, 5%) or Denisova (Fig 3: CEMP1 R80H, 0.5%) is difficult to reconcile with the fact that interbreeding of AMH with Neanderthals occurred out of Africa [75, 76]. However, as mentioned above, this could be explained by the inside Africa admixture between the ancestors of AMH and archaic hominins, or by the possible back migration of Neanderthal gene flux. Further genome analysis of the Neanderthal and Denisova polymorphisms in AMBN, ENAM, and CEMP1 certainly deserves attention as they could trace back an African ancestor common to Neanderthals, Denisova and early anatomically modern humans."

Well, it is not "difficult to reconcile" if the fact is wrong and AMH interbred with Neanderthals inside Africa...

The ENAM G389S variant is found not only in Africa at 5% but also at very low frequencies in the Americas 0.3% (maybe imported by African slaves or perhaps a genuine Amerindian-Neanderthal admixture). Its global prevalence is only 1.3% and is virtually absent in Asia and Europe. Denisovans carried the ancestral "G" type, found in chimps and gorillas. Neanderthals and modern humans carry the derived "S" type.

They also found a some proteins in Denisovans (K55 E variant) that appear at 26% frequency among Africans and 7% globally (the highest outside of Africa being in America at 2% and far lower elsewhere). This is the ancestral type, found in Denisovans, chimpanzees and modern humans, but it was not found in Neanderthals.

The paper also hints at an admixture in Africa between H. Sapiens and some archaic homo 35,000 years ago:

"Most of the amino acid changes are found in the dentin and enamel proteins that are encoded by genes located in two close clusters on the chromosome 4 (Fig 4) and supposed to derive from an ancestral gene encoding a secretory calcium-binding protein [68]. These clusters fall apart from known haplotypes on chromosome 4 and do not correspond to candidate Neanderthal or Denisovan gene flow regions in non-African living humans [69, 70]. However, a signal of archaic introgression in the locus 4qMB179 on chromosome 4 has been evidenced in Central African populations, and is supposed to result from admixture with an archaic Homo some 35 kya [71]."

Admixture with archaic hominins in Africa would "enrich" the diversity of African DNA and therefore contradict the prevailing theory that Africans are more diverse and therefore they are the "original" source of humanity.

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2018 by Austin Whittall © 

On some misconceptions regarding mutations and "antiquity"

This website in an attempt to explain DNA diversity that allows us to identify "older" genomes from more "recent" ones, says the following:

"There are parts of your (our) genome where random mutations won’t generally kill you. Random mutations tend, therefore, to accumulate there. Since have some pretty decent estimates for how often random mutations occur, comparing the mutations in two different populations lets us estimate how long ago they split. For example, let’s suppose you get one random mutation per hundred years, and we’re comparing two populations that split 300 years ago and haven’t seen each other since. Population A should have gotten 3 mutations during that 300 years, and Population B should have gotten 3 mutations. So if we look at a third population, C, and find that they have 5 mutations that they don’t share with A or B, then we conclude that C split off from some ancestral population 500 years ago. We can reconstruct this as: 600 years ago, there was a group called ABC, but 500 years ago, it split into Group AB and Group C. 300 years ago, Group AB split into Group A and Group B."

Sounds great, so clear, so logical... but... This is a typical explanation for diversity in Africa vs. out of Africa and to put it bluntly, it is Wrong!!. And this is why:

It says there was an ancestral group, ABC which split 500 years ago into AB and C. Since the split, group C accumulated 5 mutations. And group AB split 300 years ago. Each sub group, A and B, accumulated 3 mutations each, which made them different. So as C has 5 mutations but A and B only 3 each, C is "older" than A or B. Did you see the mistake in this logical explanation?

The error is that although they postulate a random mutation every 100 years, the group AB which split from ABC 500 years ago did not accumulate any mutations from then until the split of A and B 300 years ago.

AB group did not accumulate a single mutation over 200 years, but C did, it added 2.

Then, A split from B, and both of them kept on mutating at 1 mutation every hundred years. Final score: C = 5 mutations and A & B only 3.

Actualy AB would have accumulated mutations over those 200 years, different mjtations from those of C. In fact all groups A, B and C would have accumulated 5 mutations over those 500 years.

All humans are equally ancient, we all carry the original DNA, and after we split into separate groups, our random mutations led us to split apart a bit more, but we all have roughly the same amount of mutations, unless, of course these mutations are not random, but are mobilized by selection, but that will be discussed in another post.

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Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2018 by Austin Whittall © 

On the direction and root of phylogenetic trees

When I see a phylogenetic tree (also known as an evolutionary tree), I always wonder why do we believe that those branches, trunk and the root which anchors it, are correct. I ask myself why is it assumed that the mutation took place in one direction and not the other. And this trivial question is fundamental because the branches open up from other branches based on the differences between the DNA as you move along them.

Below is a very simple example of what I mean. Imagine we reach a planet, and come across a species whose DNA is sequenced and reveals the folowing genes: A, B and C.

We then take a sample of individuals, and sequence their genome. The nine individuals in our sample come from different continents and the "order" of the genes is different in each individual:

AAAAA, AACAA, BAAAA, BAAAB, BBAAA, CACAA, AACAB, BAACB and BABAB.

We assume that mutations take place at random so a B can spontaneously mutate into C or A, an A into B or C and a C into A or B. So, a group of scientists after looking at the genomes assumes that AAAAA is the oldest group of that species and that the other populations are the result of mutations that modified the original genome. They build tree (1) shown below. The most distant population is the one with the BABAB genome.

The red arrow marks the "founding" population and the green arrow the "newest" group, descended from them.

But another group of scientist based on some ancient remains and other assumptions, says "No, the original population is not AAAAA, it is the people carrying the BABAB genes" (exactly the opposite to what the first group of scientists have proposed and proven in Tree (1).

The second group builds Tree 2, where as we can see (the green arrow shows the original population and the red one shows us where they place the population AAAAA. For this second group of scholars, populations AACAB and CACAA are the "most recent" populations. The tree below shows the mutated gene in red:

Two different trees built from the same genome samples. Copyright © 2018 by Austin Whittall

The scholars could then identify haplogroups where the A to C or the B to A mutation marks a haplogroup and theorize on how these haplogroups evolved one from the other... Does this sound familiar? Yes, it is how the mtDNA and the Y chromosome DNA haplogroups were created -by adopting certain mutations as key indicators for branches and defining that it took place in a certain way (in our DNA, for instance, an aadenine (A) switch for a cytosine (C) may mark a haplogroup. A for C but, we could also -as in our thoretical planet imagine that the C switched for an A and that the supposed parent genome is actually the child and not the other way round.

Thus the "new" American genomes could actually be the oldest and the African ones the youngest (like switching from tree 1 to 2 above).

This is of course an oversimplification, but we do have the DNA of Neanderthals, Denisovans, Homo sapiens from different sites around the world, and anchors from our ape relatives, the chimps. But often, when I look at the sequences (CGACGGAATACG... and so on - see this image below (from Nature where a standard human sequence -top row "Reference"- is compared to Neandertal sequences in the bottom two rows), I wonder how true and accurate are our "reconstructions". Which base mutated first, which later?...

And also See this image, which compares Denisovan, Neandertal and some apes and monkeys.

Trees are created by computer programs that use "assumptions" and theoretical considerations built into them by the scientists that programmed them. They supposedly work using statistically sound calculations, which are so complex that I doubt anyone can verify them without the help of computer software... so maybe some bias is built into them, for instance assuming that AAAAA is the "original" genome in our distant planet, or here, assuming that the DNA of an African is "older" than that of an Amerindian...

I don't believe in snake oil, but I do believe that we should look at facts with open eyes (like the two trees that can be built using those nine sequences in our distant planet. Same data different conclusions) and not be biased by a prejudice (prejudice = Pre Judgement, we use the data to prove what we believe to be true, not to prove the facts...).

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

Heterozygosity for dummies

Heterozygosity is lower in all non-Africans when compared to Africans.

What does this mean?

First of all what is Hetrerozygosity?

Heterozygosity

We all have two copies of each gene. That is because we got half of our chromosomes (with their respective genes) from each of our parents), making one copy from each of them.

Genes come in different variants, known as alleles.

So if there are two possible alleles: "b" and "B" (one per gene) you may have any of the following combinations arising from the mixing of your parent's genes

• bb
• bB
• Bb
• BB

That is four options, two in which each gene has the same allele (bb, BB) and therefore you are Homozygous and two in which you have different alleles (bB, Bb) which makes you Heterozygous.

It is evident that homozygosity implies less genetic variability (being BB you lack the "b" allele or if you are bb, you will lack the "B" allele). And this may have consequences regarding your health and surviveability.

Populations.

We must also take into account that the proportion of "b" and "B" in can be different, in other words they are present at different frequencies: "p" and "q" respectively which are not necessarily the same.

In other words the frequency of each genotype (bb, Bb, or BB) in a given population (known as "allele frequency") will depend on the frequencies of each allele:

In a very large (infinte) population where individuals mate at random, we can calculate the allele frequency using the Hardy-Weinberg Theorem using this formula to calculate the frequencies (f) of each of the three genotypes (bb, BB, Bb):

• f(bb) = p²
• f(bB) = 2pq
• f(BB) = q²

And since they are "all" the genotypes, their sum must add up to 100% of the populaton:

100% = p² + 2(pq) +q²

Say b is present at p = 30% and B has a frequency of q= 70% (both frequencies must aldo add up to 100%), then:

100% = (30%)² + 2(30% x 70%) + 70%²

100% = 9% + 42% + 49%

So the frequency of bb alleles is only 9% meaning that 9% of the population is homozygous for b. 42% is heterozygous and 49% is homozygous for B.

But in a real world, humans don't mate randomly: they choose partners for different reasons, or, due to cultural rules may marry within their group (endogamy).

Also some homozygous alleles may cause genetic diseases such as cystic fibrosis, Tay-Sachs or phenylketonuria which may kill individuals before they become adults and reproduce, here selection is actively working to modify zygosity.

As populations are not infinte but finite, there is not an endless genetic pool, but a discrete one so in smaller or isolated populations, heterozygosity will fall due to random events (imagine adults that have no offspring, eliminating their alleles from the genetic pool).

The opposite effect is when two isolated populations admix, adding new alleles to the gene pool, increasing heterozygosity.

So, the factors that provoke homozygosity are:

• Inbreeding
• Geographic isolation
• Genetic Drift
• Cultural practices -i.e. consanguineous marriage or endogamy
• Positive evolutionary selection

It can fall, on the other hand if there is an isolation-breaking event such as the mixing of two previously isolated populations.

Let's take a look at each of these factors:

1. Interbreeding

The taboos that forbid marrying your next of kin have a genetic basis: those closely related to you will carry many genes identical to yours. Since relatives share alleles, inbreeding will bring together identical copies of an allele more frequently than breeding between unrelated mates, and this increases homozygosity:

"F", the Inbreeding coefficient is the probability that two alleles are identical copies of an allele from a common ancestor. It is also, the proportion of the population that is inbred (having two alleles identical by descent).

We can take the expression used above and adapt it to calculate the frequencies of alleles in an inbred population:

• f(bb) = p²+2Fpq
• f(bB) = 2pq (1-F)
• f(BB) = q²+Fpq

All must add up to 100% of the population.

So if inbreeding coefficient is 20%, the relative frequencies of bb, BB and Bb would be (we will use the same frequencies as in the original example: b is present at p = 30% and B has a frequency of q= 70%):

100% = (30%)² +2 x 20% x 30% x 70% + 2(30% x 70%)(1-20%) + 70%² +2 x 20% x 30% x 70%

100% = 13,2% + 33,6% + 53,3%

So the comparison is:

• bb increases from 9% to 13.2% of the population
• BB increases from 49% to 53.3% of the population
• Bb falls from 42% to 33.6% of the individuals

Heterozygosity drops due to inbreeding even though the same alleles are present.

Since some genetic traits are recessive, and manifest themselves only when the two alleles are present, that is, homozygosity for those alleles is present, inbreeding increases the frequency of these recessive traits, which could be as benign as blue vs. dark eyes or nasty as congenital diseases.

Genetic drift

Imagine a population which starts off with p = q = 50%. In other words, the proportion of B and b is identical. Applying Hardy-Weinberg Theorem we can calculate the genotype frequencies:

100% = (50%)² + 2(50% x 50%) + 50%²

100% = 25% + 50% + 25%

So50% are heterozygous (Bb) while the other half is equally homozygous: 25% are BB and 25% are bb.

But this is in an infinte population and also, the frequencies p and q are probabilities.

Real life may reflect these probabilities in a different way. Look at it this way: when you flip a fair coin there is an equal chance (p=50%) of getting heads and or tails (q=50%). But in practice we all know that you could throw 3 heads in a row and get only 2 tails in a series of five tosses. Which is not a 50 ⁄ 50 proportion. it is 66% ⁄ 40%. You may even get 3 heads in a row in a series of 3 tosses (100 ⁄ 0).

So in small series it is unlikely that the actual real frequency is close to the theoretical probability (p or q).

However, when you use larger series, for instance if you tossed the coin 1,000 times, the ratio would be closer to 50 ⁄ 50 (say 494 tails and 506 heads).

This same effect applies to the probability frequencies in small populations: two heterozygous parents (bB) could have all four offspring that are homozygous (bb) just by chance.

So, in small populations this phenomenon known as "Genetic drift" just by random forces -not by natural selection or deliberate interbreeding- can change the frequency of some alleles in very short time, making them extremely common ("Fixing them") or making them disappear.

Founder Effect

Founder events take place when a small sub-population of a larger one migrates and establishes a new settlement (hence "founder" population). It is obvious that not all the alleles present in the original population will be present in this smaller group. Those left behind will not appear in the new one, this reduces the total quantity or "allele richness" of the new subpopulation.

Liken it to randomly taking 4 M&M's from a bag holding 500 candies, it is probable that you will not pick all the available colors. So if the M&Ms in the bag are red, yellow, green, blue and brown in equal proportions, you could very well have picked: 2 yellow, 1 green, 1 red and no brown or blue candies. So this does in effect reduce the "diversity" or "richness" in the subpopulation but, it may not impact on heterozygosity:

Imagine the population we mentioned befor where 9% were homozygous for b (bb), 42% were heterozygous (Bb) and 49% were homozygous for B (BB). Now lets imagine that a small group from this original one forms a colony elsewhere, and just by chance, 60% of the individuals carry the Bb heterozygosity, while the remaining 40% are BB homozygous.

This new subpopulation will therefore have a higher heterozygosity than the original population (60% vs. 49%), but it will surely be less rich or diverse due to the alleles left behind (M&M analogy).

Founder effect impacts on the "allelic richness" by reducing it but it may no have much effect on hetrerozygosity. This is because the richness is based on the presence of the alleles and not on the internal diversity within them. A rare allele lost during a founder effect reduces the diversity but will probably have little impact on heterozygosity.

Bottleneck

This is a drastic reduction in a population. It could be caused by disease or a natural catastrophe (drought, volcanic eruption, fire, Ice Age, global warming).

Those that survive will carry only part of the genetic diversity of the original population, as those lineages that perished, are gone forever. But this does not mean that heterozygosity drops. Actually, allelic richness falls faster than heterozygosity because bottlenecks usually wipe out ,any low-frequency alleles and this causes an excess of heterozygosity in selectively neutral loci compared to normal populations subjected to genetic drift.

Leberg (1992) investigated loss of heterozygosity and allelic variation experimenting with mosquitofish and found that a decrease in heterozygosity only happens when the bottleneck is extreme and prolonged.

Selection

After the population reduction in founder effects or Bottlenecks & Geographic Isolation (which may also lead to inbreeding due to the smaller population), diversity will increase again due to chance mutations.

Another factor that may modify the genetic patterns is Natural Selection: the bottleneck may have caused the fittest to survive -imagine a disease that those equipped with some genetic advantage manage to survive while the others perish- and therefore selection increases the frequency of certain genes in the new population, when compared to the pre-bottleneck one.

Geographic Isolation

Similar to Bottlenecks, it is the separation of one group from the main population, as when there is a founder event.

Heterozygosity and Human Evolution

So when defenders of the "Out of Africa" theory use heterozygosity to support an African origin for Mankind, they point out that Africans have the highest heterozygosity of all human populations: the others (non-Africans) have lost it as they migrated out of Africa in small bands (founder effect), separated widely (geographic isolation), were more prone to fall prey to natural catastrophe (bottle necks), inbred more frequently as they were smaller populations and in doing so lost heterozygosity which the original basal population in Africa retained.

An example of this is shown in the image below which charts "heterozygosity vs. distance from Africa (Addis Ababa)" (from [1]):

This chart from [5] show more or less the same information:

Allelic Diversity

Having said this, we must point out that "Genetic Diversity" is not only measured by heterozygosity but also by the "number of alleles" present in a given population, that is "allele richness" or "allelic diversity" which is calculated as the average number of alleles per locus.

In other words a population may have a high heterozygosity compared to another and supposedly be "more diverse" but, overall have a lower number of alleles which makes it definitively "less diverse".

An example of this paradox is shown in this paper (Begoña Martínez-Cruz et al., In the heartland of Eurasia: the multilocus genetic landscape of Central Asian populations [1]) which has interesting data in its Table 2 which shows the "Average AR" - allelic richness- and "expected heterozygosity He" for each of the 26 Central Asian populations and other nearby regions:

AR He   Population
12.66 0.819 Central/South Asia
 8.60 0.820 Central Asia - TJK
 8.50 0.812 Central Asia - TJT
 8.50 0.774 Central Asia - UZB

The first two have the same He (heterozygosity) of around 0.82 but notably different allelic diversity (12.66 vs 8.60). The last two have the same allelic diversity (8.5) but different He (0.812 vs. 0.774).

Populations can have a richer genome despite having a lower heterozygosity, of course they could have mutated faster than another population and therefore increased the diversity in their genome adding new variants.

Does this mean higher heterozygosity in Africa mean that it is the cradle of humanity?

It means that heterozygosity is higher there. Just look at the archaic hominins, Neanderthals and Denisovans. Their heterozygosity is far lower than that of any extant human group, but we know that they predate Homo sapiens by several hundreds of thousands of years. They are less heterozygous but older and ancestral:

Prüfer et al. paper on Neanderthals [3] confirms this (highlighted in bold):

"The Neanderthal autosomal genome carries 1.7–1.8 heterozygous sites per 10,000?bp (Supplementary Information section 9). This is 84% of the number of heterozygous sites in the Denisovan genome, 22–30% of that in present-day non-African genomes, and 16–18% of that in present-day African genomes (Extended Data Fig. 1). When regions of homozygosity longer than 2.5?cM stemming from recent as well as long-term inbreeding in the Neanderthal are removed, 2.1–2.2 sites per 10,000 are heterozygous, similar to what is observed in the Denisovan genome. Thus, heterozygosity in Neanderthals as well as Denisovans appears to have been lower than in present-day humans and is among the lowest measured for any organism" [3]

Another paper by Meyer et al. on Denisovans [4] found the same diminshed heterozygosity:

"Denisovan genetic diversity. The high quality of the Denisovan genome allowed us to measure its heterozygosity, i.e., the fraction of nucleotide sites that are different between a person's maternal and paternal genomes (Fig. 5A). Several methods indicate that the Denisovan heterozygosity is about 0.022%. This is ~20% of the heterozygosity seen in the Africans, ~26 to 33% of that in the Eurasians, and 36% of that in the Karitiana, a South American population with extremely low heterozygosity. Because we find no evidence for unusually long stretches of homozygosity in the Denisovan genome, this is not due to inbreeding among the immediate ancestors of the Denisovan individual. We thus conclude that the genetic diversity of the population to which the Denisovan individual belonged was very low compared with that of present-day humans." [4]

This leads me to ask, what if African heterozygosity was enriched by recent admixture with other hominins in Africa? an inflow of different relic alleles elevated African diversity above that of non-Africans. Could current lower Amerindian heterozygosity reflect an ancient population just like that of Denisovans or Neanderthals?

We will look into these questions in my next post when we go over some recent papers on the possibility of an ancient Out of Africa event whose genes ended up in contemporary Papuans and Australians.

Sources

[1] Begoña Martínez-Cruz, Renaud Vitalis, Laure Ségurel, Frédéric Austerlitz, Myriam Georges, Sylvain Théry, Lluis Quintana-Murci, Tatyana Hegay, Almaz Aldashev, Firuza Nasyrova and Evelyne Heyer, In the heartland of Eurasia: the multilocus genetic landscape of Central Asian populations, European Journal of Human Genetics (2011) 19, 216–223; doi:10.1038/ejhg.2010.153; published online 8 September 2010.
[2] Paul Verdu, Trevor J. Pemberton, Romain Laurent, Brian M. Kemp, Angelica Gonzalez-Oliver, Clara Gorodezky, Cris E. Hughes, Milena R. Shattuck, Barbara Petzelt, Joycelynn Mitchell, Harold Harry, Theresa William, Rosita Worl, Ripan S. Malhi Patterns of Admixture and Population Structure in Native Populations of Northwest North America, PLOS Published: August 14, 2014 http://dx.doi.org/10.1371/journal.pgen.1004530
[3] Kay Prüfer, Fernando Racimo, Nick Patterson, Flora Jay, Sriram Sankararaman, Susanna Sawyer, Anja Heinze, Gabriel Renaud, Peter H. Sudmant, Cesare de Filippo, Heng Li, Swapan Mallick, Michael Dannemann, Qiaomei Fu, Martin Kircher, Martin Kuhlwilm, Michael Lachmann, Matthias Meyer, Matthias Ongyerth, Michael Siebauer, Christoph Theunert, Arti Tandon, Priya Moorjani, Joseph Pickrell, James C. Mullikin et al., The complete genome sequence of a Neanderthal from the Altai Mountains, Nature 505, 43–49 (02 January 2014) doi:10.1038/nature12886
[4] Matthias Meyer et al. A High-Coverage Genome Sequence from an Archaic Denisovan Individual, www.sciencemag.org SCIENCE VOL 338 12 Oct 2012
[5] Keith Hunley, Claire Bowern, Meghan Healy, Rejection of a serial founder effects model of genetic and linguistic coevolution, Published 1 February 2012.DOI: 10.1098/rspb.2011.2296

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

Denisovans. More information on their genetics

A paper by S. Sawyer et al., Nuclear and mitochondrial DNA sequences from two Denisovan individuals, PNAS, doi: 10.1073/pnas.1519905112 Published Nov. 16, 2015 has sequenced the nuclear and mtDNA of two Denisovans. Their findings are the following:

Abstract
Denisovans, a sister group of Neandertals, have been described on the basis of a nuclear genome sequence from a finger phalanx (Denisova 3) found in Denisova Cave in the Altai Mountains. The only other Denisovan specimen described to date is a molar (Denisova 4) found at the same site. This tooth carries a mtDNA sequence similar to that of Denisova 3. Here we present nuclear DNA sequences from Denisova 4 and a morphological description, as well as mitochondrial and nuclear DNA sequence data, from another molar (Denisova 8) found in Denisova Cave in 2010. This new molar is similar to Denisova 4 in being very large and lacking traits typical of Neandertals and modern humans. Nuclear DNA sequences from the two molars form a clade with Denisova 3. The mtDNA of Denisova 8 is more diverged and has accumulated fewer substitutions than the mtDNAs of the other two specimens, suggesting Denisovans were present in the region over an extended period. The nuclear DNA sequence diversity among the three Denisovans is comparable to that among six Neandertals, but lower than that among present-day humans.

Take note of how large the Denisovan teeth are. From the paper

The paper notes that "Both Denisova 8 and Denisova 4 are very large compared with Neandertal and early modern human molars, and Denisova 8 is even larger than Denisova 4. Only two Late Pleistocene third molars are comparable in size: those of the inferred early Upper Paleolithic modern human Oase 2 in Romania and those of ObiRakhmat 1 in Uzbekistan"

The teeth though primitive looking also seem to differ from H. erectus teeth too. Which is quite interesting.

Denisova 8 is about 60,000 years older than Denisova 3 and Denisova 4 meaning that they are 110,000 years old. This is a long period of time in a same location.

The paper says the following about this long occupation: ", suggests Denisovans were present in the area at least twice, and possibly over a long time, perhaps interrupted by Neandertal occupation or occupations. Denisovans may therefore have been present in southern Siberia over an extended period. Alternatively, they may have been present in neighboring regions, from where they may have periodically extended their range to the Altai.".

The paper ends with an open question: " Given that the high-coverage genome from the Denisovan 3 phalanx carries a component derived from an unknown hominin who diverged 1–4 million years ago from the lineage leading to Neandertals, Denisovans, and present-day humans, it is possible that this component differs among the three Denisovan individuals. In particular, it may be that the older Denisovan population living in the cave carried a larger or different such component. It is also possible that the two diverged mtDNA lineages seen in Denisova 8 on the one hand and Denisova 3 and Denisova 4 on the other were both introduced into the Denisovans from this unknown hominin, as has been suggested for the mtDNA of Denisova 3. However, more nuclear DNA sequences from Denisovan specimens of ages similar to Denisova 4 and Denisova 8 are needed to address this question fully.".

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

More on Amerindians and Austro-Melanesians

Another paper on the peopling of America (Maanasa Raghavan, et al., (2015) Genomic evidence for the Pleistocene and recent population history of Native Americans Science, 23 July 2015 / Page 1 / 10.1126/science.aab3884) proposes that "the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (KYA), and after no more than 8,000-year isolation period in Beringia. Following their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 KYA, one that is now dispersed across North and South America and the other is restricted to North America."

No early peopling here, no ancient archaic Denisovans or pre-East Asians entering America long ago.

The founding populations were isolated in Beringia and then entered America and that is all there is to it!

But... they do recognize that some Native Americans are close to Austro-Melanesians:

"We found that some American populations, including the Aleutian Islanders, Surui, and Athabascans are closer to Australo-Melanesians compared to other Native Americans, such as North American Ojibwa, Cree and Algonquin, and the South American Purepecha, Arhuaco and Wayuu (fig. S10). The Surui are, in fact, one of closest Native American populations to East Asians and Australo-Melanesians, the latter including Papuans, non-Papuan Melanesians, Solomon Islanders, and South East Asian hunter-gatherers such as Aeta (fig. S10).
We acknowledge that this observation is based on the analysis of a small fraction of the whole genome and SNP chip genotype datasets, especially for the Aleutian Islander data that is heavily masked due to recent admixture with Europeans (28), and that the trends in the data are weak.
Nonetheless, if it proves correct, these results suggest there may be a distant Old World signal related to Australo Melanesians and East Asians in some Native Americans. The widely scattered and differential affinity of Native Americans to the Australo-Melanesians, ranging from a strong signal in the Surui to much weaker signal in northern Amerindians such as Ojibwa, points to this gene flow occurring after the initial peopling by Native American ancestors."

So they recognize the strong links between Austro - Melanesians and Amerindians but suggest it happened after the peopling of America... and that the signal may be due to a limited analysis of the genome (the small sample tested by some statistical fluke gives a high relationship between both populations, but maybe a larger sample of the genome may yield a different outcome).

I find this conclusion rather odd: "The widely scattered and differential affinity of Native Americans to the Australo-Melanesians, ranging from a strong signal in the Surui to much weaker signal in northern Amerindians such as Ojibwa, points to this gene flow occurring after the initial peopling by Native American ancestors".

Odd because it can also be interpreted as follows: South American Natives have a higer signal of Austronesian genes because they are what is left of an ancient migration that was overwhelmed by East Asians in North America.

The tide of Siberian people replaced almost all Austronesian genes in North America and also in South America but those living in relative isolation in the Amazon retained some of the original genes...

Both (theirs and mine) theories explain the gradient (high in S. America - low in N. America) in the Austronesian genetic signal... so which is the best explanation?

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

Denisovans Amerindians and Austronesians

A paper by Pengfei Qin and Mark Stoneking (Denisovan Ancestry in East Eurasian and Native American Populations bioRxiv preprint first posted online April 3, 2015; doi: http://dx.doi.org/10.1101/017475), takes a look at the Denisovan content in modern Homo sapiens genes.

Below is one of the maps posted in the supporting information (from page 8) which shows (blue shades) the higher introgression of Denisovan DNA into humans in Australia, New Guinea and Melanesia, while the Neandertal content is given by the red shades (higher in Asia, America and Europe. Green tint is the neutral African area.

Neandertal and Denisovan DNA in modern humans. From Fig. S4 B in Pengfei and Stoneking.

They put forward two possible ways for the admixture of Denisovan and Homo sapiens genes. Allow me to quote them:

"However, there are (at least) two potential alternate scenarios that could explain these results. First, Denisovan admixture could have occurred in a population that was ancestral to both EE/NA (East Asia and Native American) and Oceanian populations; second, admixture could have occurred in a population that was ancestral specifically to Mamanwa, Australians, and New Guineans (as suggested previously (2)), followed by a back-migration from New Guinea to mainland East Asia. This putative back-migration would then have spread both New Guinea and Denisovan ancestry throughout East Asia and Siberia, and ultimately to the Americas."

The first option (admixture in Siberia near Denisova), would be followed by additional dilution in East Asia of Denisovan genes when more modern humans migrated into East Asia and admixed with the population that had originally received the Denisovan input. While this did not take place in Oceanian peoples.

In my opinion the back-migration out of Australia is unlikely. But what if... there was a sizeable populations of Denisovans in South East Asia and Sahul. Humans arrived and mixed with them. The higher the density of Denisovans or ratio of Denisovans to H. sapiens, the higher their "input" of genes into the mixed offspring of human - Denisovan matings. So PNG, Australia had a higher ratio of Denisovans than East Asia... or America (why must we always assume that the introgression took place once in one place?). Because admixture could have taken place in several locations: America, Asia and Austronesia.

Who are these Denisovans? The most likely candidate is an ancestor that lived in Asia and had left Africa before Humans and before Neandertals... that spells Homo erectus. They did live in Sahul and China (maybe America but that is not considered by mainstream science).

The interesting thing is that Neanderthal (see the red hues in the map above) genes are very strong in America among Native Americans too, suggesting (a) Modern Humans mixed with them in Asia and brought the Neandertal genes with them into America or (b) Admixture took place in America: modern humans met and mated with Neandertals in the New World.

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

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 © 

Deeply Admixed East Asians and Neanderthals

A pair of papers behind paywalls deal with the issue of Neanderthal and Human admixture. I will share both abstracts:

1Complex History of Admixture between Modern Humans and Neandertals, Benjamin Vernot and Joshua M. Akey DOI: http://dx.doi.org/10.1016/j.ajhg.2015.01.006:

Recent analyses have found that a substantial amount of the Neandertal genome persists in the genomes of contemporary non-African individuals. East Asians have, on average, higher levels of Neandertal ancestry than do Europeans, which might be due to differences in the efficiency of purifying selection, an additional pulse of introgression into East Asians, or other unexplored scenarios. To better define the scope of plausible models of archaic admixture between Neandertals and anatomically modern humans, we analyzed patterns of introgressed sequence in whole-genome data of 379 Europeans and 286 East Asians. We found that inferences of demographic history restricted to neutrally evolving genomic regions allowed a simple one-pulse model to be robustly rejected, suggesting that differences in selection cannot explain the differences in Neandertal ancestry. We show that two additional demographic models, involving either a second pulse of Neandertal gene flow into the ancestors of East Asians or a dilution of Neandertal lineages in Europeans by admixture with an unknown ancestral population, are consistent with the data. Thus, the history of admixture between modern humans and Neandertals is most likely more complex than previously thought.

In other words Europeans and East Asians carry Neanderthal genes but this cannot be explained by a reduction of Neanderthal genes in Europeans due to the forces of Natural selection. Instead it may be due to either of the following: (i) a second admixture with East Asians and ⁄ or (ii) European admixture with another "ancient" population which watered down the Neanderthal component.

Either option is interesting, there have been hints at an archaic admixture event with a yet to be defined ancestral group (H. erectus? Denisovans?). Additionally Neanderthal presence is strong among East Asians and, may I point out: Amerindians. And this is surely due to a "deeper" admixtwure event.

2.Benjamin Vernot, Joshua M. Akey, Complex History of Admixture between Modern Humans and Neandertals The American Journal of Human Genetics, Available online 12 February 2015.

It has been hypothesized that the greater proportion of Neandertal ancestry in East Asians than in Europeans is due to the fact that purifying selection is less effective at removing weakly deleterious Neandertal alleles from East Asian populations. Using simulations of a broad range of models of selection and demography, we have shown that this hypothesis cannot account for the higher proportion of Neandertal ancestry in East Asians than in Europeans. Instead, more complex demographic scenarios, most likely involving multiple pulses of Neandertal admixture, are required to explain the data.

More evidence to the multiple admixture event in East Asia.

These papers make me wonder about the geographic range of Neanderthals.They have been found in Altai, but surely they expanded well East, into East Asia, Beringia and, why not? America.

Did they admix in the New World and back migrations returned their DNA to East Asia? Are the current time frames correct? When did these multiple admixtures take place? Are we to believe that they took place in the 60 -30 ky window between the purported Out of Africa event and the demise of the Neanderthals?

Additional studies will surely settle these issues.

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

Epigenetics, a new twist to inheritance

During a recent trip abroad, to kill the long hours of flight time, I bought a Scientific American -something I have done for the last 15 years, I always buy a Sci Am. when I fly. And besides a very intersting though probably far fetched article on the origin of our universe as the outcome of a stellar implosion in a four dimensional universe that lies beyond ours... I read an article on epigenetics.

I had never imagined that stress and chemicals can alter the switching-on and off of our genes without modifying our genetic code. The article proved that it can happen and in consequence, be a powerfull force driving evolution, one that is not recorded in our DNA.

Among the factors mentiones are, of course, the harmful chemicals and pesticides (DDT for instance) generated by our modern society. Pollutants cause mice to pass on disorders to their descent, not only their direct offspring but also to their great-great-grand-pups. And this without any trace in DNA changes.

Hunger and other causes of stress also alter the actions of genes. And this is intersting, because environmental factors, naturally occuring ones could impact on the inhibition or activation of our genes and be driving forces behind the evolution of species. The article summarizes this as follows:

If the environment can sometimes directly produce longterm, transgenerational changes in gene activity without first altering the DNA coding sequence, then the classical view of evolution ... wil have to be expanded.
... Epigenetic changes appear to occur 1,000 times more frequently [than advantageous genetic mutations]... Natural selection would then pick the best adapted among them to thrive and carry on - genome, epigenome, and all.

I am still pondering over this thought, because it does have direct impact in Human evolution: starving and stressed humans would have been very common during most of mankind's history (beasts and natural events causing famine, illness and death). And this would have prompted subgroups a and b of population A to survive while subroups c to n died out. All of them had the same DNA but a and b had some genes activated which gave them the edge and they survived...

How does this impact on the "molecular clock"?

Further Reading
A New Kind of Inheritance, Michael K. Skinner, pp. 45-51. Scientific American, Aug. 2014 vol 311, No. 2.

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

Homo Erectus and a recent admixture with modern humans

January is mid Summer in Argentina, holiday season so I have taken some time off to read and relax. And as usual I found an interesting article: Alan R. Rogers and Ryan J. Bohlender Bias in Estimators of Archaic Admixture, 23.Dec.2014. I will not bore you with the technical matters, I will go straight to the point:

Rogers and Bohlender take a look at the methods and assumptions used in estimating admixture of ancient humans (Denisovans and Neanderthals) in modern H. sapiens. They noticed that these methods "are sensitive to “ghost” admixture, which occurs when a population receives archaic DNA from sources not acknowledged by the statistical model". They detail different estimators and take the cases of Europeans and Melanesians for Neanderthal and Denisovan admixture to check their hypothesis.

They do find that " Such comparisons indicate that archaic gene flow into Europe came primarily from Neanderthals and support the view that archaic populations were much smaller than those of early modern humans, which supports their theory but, when it comes to Melanesians: they expose an inconsistency, and point out that "Although this inconsistency may be a statistical artifact,it could also result from an incorrectly specified model. For example, Homo erectus may have contributed genes to populations of Denisovans (Prüfer et al., 2014, p. 48) or to modern humans in Melanesia (Mendez et al., 2012)."

This is a very interesting conclusion, I don't recall having read anyone suggest that H. erectus mingled with Denisovans or with modern Humans in Melanesia... but it is, and always has been the best explanation.

How did the genes of a group of Denisovans living in Altai get into the lineages of a coast-hugging migration Out Of Africa on its way to Melanesia? If the ancestors of Melanesians did not cross the Himalaya and other mountain ranges to reach Altai then the Denisovans had to do the same, in the opposite direction... and this does not sound reasonable.

The simple explanation: a group of humans (H. erectus) who have been living in South East Asia and China for over one million years were the common link between Denisovans and Melanesians. They were directly in the path of the migrating humans. Ergo they admixed, humans and erectus.

And this is exactly what I suggested over a year ago in my post of Dec. 21, 2013 Denisovans interbred with Homo erectus after reading Prüfer et al. paper.

I had not seen, however, the other paper mentioned by Rogers and Bohlender:

Mendez, F. L., Watkins, J. C., Hammer, M. F., 2012. Global genetic variation at OAS1 provides evidence of archaic admixture in Melanesian populations. Molecular Biology and Evolution 29 (6),1513–1520.)

So I looked it up and read it, and to my surprise, they (Mendez, Watkins and Hammer) reached the same conclusion outlined above:

Another unanswered question concerns how gene flow occurred given the large geographic distance between the Denisova archeological site in the Altai Mountains and the likely route of migration of Melanesian ancestors. It is unclear whether individuals carrying Denisova-like sequences in the Altai region contributed directly or shared some genetic variation with the population that contributed to the ancestry of Melanesians.

Then they try to identify the source: " we suggest that the archaic ancestor contributing the deep lineage to Melanesians and the specimen from Denisova were members of genetically differentiated populations. Interestingly, the coalescent time of the human reference and deep lineage of 3.3 Ma is much older than the population divergence time of ∼0.3 Ma for humans and Denisova suggested by Reich et al. (2010).... These observations present the intriguing possibility that this deeply diverged region of OAS1 may have introgressed into the common ancestor of Denisova and Melanesians via admixture with an unsampled hominin group, such as Homo erectus. In fact, the introgression of a more archaic form into the ancestors of Denisova was also considered by Reich et al. (2010) to explain some archaic morphological features of the Denisova molar. However, without DNA from this “ghost” population or evidence from other loci showing a similar pattern of extreme haplotype differentiation, such a scenario is speculative.".

So what we need is DNA from H. erectus, for comparison, something which may be very unlikely, but who know, maybe a relatively recent H. erectus fossil may be found with viable DNA for sequencing... After all if the H. floresiensis survived until 17 kya, maybe H. erectus did so too... after all, they had to be there, in person, to introgress with humans.

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