Another post on dental enamel protein AMBN 273V or M in Denisovans, Neanderthals, and Humans

In three different posts I mentioned dental enamel protein as a tool to investigate ancient ancestry, admixtures, and archaic introgressions.

The first post looked into a paper by Quiamei Fu, et al., 2026, Enamel proteins from six Homo erectus specimens across China, published in Nature on May 13, 2026 (vol. 655, pp 141–147 https://doi.org/10.1038/s41586-026-10478-8), it suggests archaic introgression from Homo erectus into Denisovans, and from them, into modern humans, which shared a protein found in teeth enamel, named AMBN(M273V) from erectus via Denisovans to us, Homo sapiens.

The second post mentioned another protein found in teeth, called COL17A1 that is found in its ancestral form in Paranthropus robustus and Homo naledi, and in derived form in--Denisovans, Neanderthals, and modern humans. Suggesting that naledi may not be a homo (see Madupe P, Taurozzi A, Koenig C., et al., Proteomic analysis of dental enamel from 20 Homo naledi individuals shows no male markers. Cell, 2026; 189, 4415-4424.e11).

The third post mentioned another recent paper that questions the archaic introgression hypothesis proposed by Fu et al. and suggesting other alternatives for the presence of AMBN 237V in Denisovans and humans, that don't require an introgression with Homo erectus (see No signal of a super-archaic origin of the Denisovan AMBN gene, a comment on the protein affinity of Homo erectus and Denisovan enamel proteins, Ioannis Patramanis, Frido Welker, Laurits Skov. bioRxiv 2026.08.11.744165; doi: https://doi.org/10.64898/2026.08.11.744165).

Today I will discuss a fourth paper on the subject of dental enamel proteins, published last week, on August 26, 2026 by Paula Kotli; Enamel Palaeoproteomics Successfully Distinguishes between Denisovans and European Neandertals (bioRxiv 2026.08.22.746388; doi: https://doi.org/10.64898/2026.08.22.746388).

Kotli compared DNA from the Penghu jawbone, dredged up from the sea in Taiwan, and a Neanderthal from Portugal and found that the AMBN V273 variant (with a Valine aminoacid substitution there —hence the "V") was exclusively Denisovan while the Neanderthal carried a Methionone aminoacid there (M273 variant). These two proteins can serve as markers to identify the origin of ancient teeth when DNA is not correctly preserved; tooth peptides last longer than DNA.

Most modern humans carry the M273 variant, shared with Neanderthals, while not only Penghu, but other Denisvoans (like the Denisova 3 specimen) carry the V273 variant. Unsurprisingly, the region with the highest levels of Denisovan admixture, the Philippines, also has the highest level among all modern humans of the V273 variant: It reaches "a notably elevated frequency of ∼21% in modern Philippine populations (compared to <1% globally)."

Africans and archaic admixture

While researching about ancient teeth proteins and their prevalence among modern humans, Neanderthals, and Denisovans, I came across a good paper on the subject: Zanolli C, Hourset M, Esclassan R, Mollereau C. Neanderthal and Denisova tooth protein variants in present-day humans. PLoS One. 2017 Sep 13;12(9):e0183802. doi: 10.1371/journal.pone.0183802. PMID: 28902892; PMCID: PMC5597096. In it, they mention the presence of rare variants found in Denisovans and Neanderthals, inside Africa. This is quite unexpected because both of those ancestral lineages are not known to have existed within Africa and the current view is that they admixed with the humans that left Africa in the Out of Africa migration. So, how did these rare variants find their way into the genes of Africans?

Zanolli et al. write (highlight is mine): "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. 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" The final comment is expected: these rare alleles could be the faint trace of the last common ancestor shared by Humans, Neanderthals, and Denisovans. I choose to believe that they are the result of admixing between archaics and recent Africans within Africa.

The ENAM G389S variant is, according to the supplementary material found at rates of zero in Europe, South Asia, and East Asia, at 5% in Africans, and at 0.3% in America. So how did it exist in Neanderthals but leave no trace elsewhere, but in Africa and America (Maybe slave trade brought it to America?). The other variant, the Denisovan CEMP1 R80H is found at zero levels everywhere except Africa where it reaches 0.5%. Denisovans in Africa?

K 55 E variant

Another ancient (ape variant) is found at surprisingly high levels in Africa, with 26%, but only at 2% in Americas, 0.2% in Europe, zero in East Asia, and 0.1% in South Asia. This variant is known as K55E (rs13331643) in CEMP1, and is commonly shared in this ancestral form with gorillas and chimpanzees.

So, basically, all modern humans in the rest of the world carry the derived allele of K55. Surprisingly, the ancestral variant, found in Africa at 26% frequency, is also found in Denisovans and Neanderthals. Again, a contradiction to the belief that Africans never mingled with those hominins.

The paper tries to explain this incongruity as follows (note that AMH means "anatomically modern humans"): "This suggests that the ancestral variant may have not been favorable to AMH outside Africa or, conversely, that the derived allele was specific to AMH and evolved out of Africa due to a founder effect. The ancestral archaic variant could also explain in part the tendency of people with African origins to have larger crowns and root volume and surface. Indeed, this variant is also found in Neanderthals teeth, characterized by high crown dimensions and frequent taurodontism. The presence of this variant in Denisova is also compatible with such traits."

Why would the non-Africans, who mated with Neanderthals and Denisovans not uptake their ancestral K55 variant in higher frequencies, and instead retain a mutation (the derived form), while Africans, who supposedly never met the Neanderthals & Denisovans, carry the ancestral variant?

I don't see how this fits in with the Out of Africa theory. The admixing of Denisovans in Asia can explain its presence there, and also in America, and Europe where Neanderthal admixture is higher, but why is it so prevalent in Africa? Maybe, the cause is an introgression of super-archics into the recent African populations.

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

Denisovans may not have admixed with erectus after all

A preprint published on August 11th, 2026 proposes an alternate explanation to the teeth protein shared by Denisovans and Homo erectus, suggesting different scenarios that could result in the same outcome and not require admixture or introgression from erectus into Denisovans.

This article was published in the non-peer-reviewed bioRxiv: No signal of a super-archaic origin of the Denisovan AMBN gene, a comment on the protein affinity of Homo erectus and Denisovan enamel proteins, Ioannis Patramanis, Frido Welker, Laurits Skov. bioRxiv 2026.08.11.744165; doi: https://doi.org/10.64898/2026.08.11.744165 and disputes the claims put forward by Quiamei Fu, et al., 2026, Enamel proteins from six Homo erectus specimens across China, Nature, https://doi.org/10.1038/s41586-026-10478-8

Background

Last May, I posted about the original paper by Fu et al., that reported that a variant of a tooth enamel protein (AMBN) found in 400,000 year-old Homo erectus specimens, known as (M273V) was also found in Denisovans, suggesting a "super-archaic introgression, some of which later passed to modern humans, are likely to have originated from H. erectus. Late Middle Pleistocene H. erectus may have coexisted with Denisovans in parts of East Asia, where these interactions are presumed to have occurred." However, this new research suggests other alternatives.

The image below is from the original paper (Fig. 4) and it shows "a possible model of gene flow related to AMBN(M273V) among H. erectus associated with the populations of Zhoukoudian, Hexian and Sunjiadong, Denisovans and modern humans." The red hexagon represents AMBN(M273V), which passes (right to left) from erectus into Denisovans, and through them, into modern humans.

The image also shows a new allele found only in erectus (yellow pentagon), called AMBN(A253G) absent in all other hominins (Denisovans, Neanderthals, Dmanisi, Homo antecessor, and modern humans).

Now those findings are disputed

The new paper by Patramanis et al., says that the erectus admixutre explanation of Fu et al., is based on an assumption: that the AMBN (M273V) variant found in Denisovans has a super-archaic origin (via erectus). The authors suggest that it isn't super-archaic. Instead, they say, there are four different possible explanations for the presence of that variant in both Denisovans and modern humans.

Below is Fig. 1 from Patramanis, 2026, with the alternatives B, C, D, and E, that could explain the presence of the allele. Alternative (A) is the one shown further up, in Fu et al.

These are the four possible alternatives:

• (B). In this case, the variant appears, by chance in Denisovans, who in turn pass it on to H. erectus and modern humans. In this case, the allele is relatively recent, and not super archaic. The erectus also carry their specific variant, AMBN(A253G).
• (C). The allele is Denisovan. That have admixed with erectus and received AMBN(A253G). This group is mistaken by Fu et al. to be erectus. They are actually admixed Denisovans.
• (D). This model is one where Homo erectus did not admix at all with Denisovans. The Denisovans are a structured population, and some carry the AMBN(A253G), others carry the AMBN (M273V), some carry the two or none.
• (E). This alternative excludes admixtures. The variant was present in the common ancestors of Denisovans, Neanderthals, erectus), but through incomplete lineage sorting (ILS), by chance this variant was only inherited by erectus and Denisovans, but not by Neanderthals or Homo sapiens. Later admixing passed it from Denisovans into modern humans.

I favor the original theory. Denisovans lived in East Asia, and had plenty of time to admix with erectus there. Let's wait for Fu et al.'s reply to this paper, and see what future research finds.

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

Homo antecessor and its relationship with Neandethals, Denisovans and Humans

Covid-19 is disrupting the lives across the world with its path of sickness and death spreading globally. But science continues. Today I post about an article published in Nature this week: Welker, F., Ramos-Madrigal, J., Gutenbrunner, P. et al. The dental proteome of Homo antecessor Nature (2020). https://doi.org/10.1038/s41586-020-2153-8.

The authors studied proteins from the teeth enamel -which degrade slower than DNA. These proteins came from a specimen of Homo antecessor, a hominin that lived in Spain (Atapuerca) 800 kya, and Dmanisi Homo erectus (1.77 My old). They compared them to those of Modern Humans, Neanderthals and Denisovans.

Their abstract highlights the following (quote):

• "H. antecessor is a close sister lineage to subsequent Middle and Late Pleistocene hominins, including modern humans, Neanderthals and Denisovans."
• "The modern-like face of H. antecessor—that is, similar to that of modern humans—may have a considerably deep ancestry in the genus Homo, and that the cranial morphology of Neanderthals represents a derived form."

The trees built by the authors show that both Dmanisi and Antecessor are part of our tree, but both lie on branches that do not lead to us. We branched from them. More evidence is needed to find these homins who cover the gap between us and them.

Note that the protein from the Dmanisi erectus was too damaged to provide useful information.

Keep safe, wash your hands, wear a mask and practice social distancing.

Written in an Argentina in isolation and lockdown.

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