Blood Groups support an "Into Africa - Out of Eurasia" migration of modern humans

Rereading a research paper published in January 2025 (Mazières S, Condemi S, El Nemer W, Chiaroni J. Rapid change in red cell blood group systems after the main Out of Africa of Homo sapiens. Sci Rep. 2025 Jan 23;15(1):1597. doi: 10.1038/s41598-024-83023-0. PMID: 39848961; PMCID: PMC11757997), I noticed that the authors attempted to adapt the facts to the Out of Africa theory even though they point in an opposite direction.

The abstract states that "we noted that the blood group allele diversity in the Neandertals remained unchanged since 120,000 yBP, while H. sapiens conquered Eurasia with blood group alleles presently exclusive to non-African populations, suggesting they may have differentiated right after the Out of Africa, between 70,000 and 45,000 yBP. Notably, Ust’Ishim possessed unknown alleles that may illustrate the lost genetic heritage of the early Eurasians. Lastly, Neandertals shared a unique Rh haplotype from which we updated the current RHD phylogeny."

The paper notes that the oldest modern humans in Eurasia carry red blood cell variants that are absent in Africans: "the oldest genomes available (Ust’Ishim, Bacho Kiro, Zlaty Kun, Tianyan, Oase1, Kostenki14, 36-45 ka) show that H. sapiens entered in Eurasia with a set of functional alleles absent in Neandertals and Denisova, and already derived from their ancestral state... Presently, some of these blood group alleles are only found in non-African populations."

How could this be possible? If humans originated in Africa, the original pool should be found there, and the Eurasians, after a bottleneck due to the Out of Africa migration, should have fewer original variants. But instead, they find none of these variants in Africa.

The paper invents a standstill in Iran, the "Persian Standstill" where the new Eurasian humans evolved their own, distinct variants! Below is the paper's text:

"Given the wide distribution of the derived alleles amongst the earliest H.sapiens of Eurasia coupled with their total absence in Africa, a first scenario could assume that these alleles have emerged in African H. sapiens before the Out of Africa, spread in Eurasia, then disappeared in Africa only. It would be tempting to point to natural selection, but the joint disappearance of independent alleles coding for phenotypes of a wide variety of susceptibility to natural selection is unlikely. Moreover, given that the highest gene diversity is found in Africa and that the expansion of H.sapiens is characterized by an initial founder effect, these alleles should be found in African populations. An alternative could be an outbreak of red cell blood group alleles outside Africa right before the conquest of Eurasia. Genetic, lithic and paleoecological evidence from the Initial Upper Paleolithic indicated that the late phase of H. sapiens expansion outside Africa circa 70 − 60,000 years ago was followed by a standstill of at least 15,000 yBP in the Persian Plateau. Analogously to the Beringian occupation ca. 20,000 yBP during which the Beringian populations paused several millennia and differentiated before entering the Americas with genetic polymorphisms shared by Native Americans only, H. sapiens could have resided long enough in the Persian Plateau to differentiate. This view makes Western Asia a good candidate for the place of incubation of the functional ABO*O.01.02, FY*01, RHCE*03, KEL*02.07, FUT1*01.02 c.35 C > T, and GYPB*04 before expansion towards East (Tianyaun), North (Zlatý kůň, Ust’Ishim) and Western Eurasia (Oase1, Bacho Kiro) more than 45ky ago."

Why propose a standstill in Persia? An unexplored alternative is that humans originated in Eurasia, and lost part of their diversity as they migrated out of Asia and into Africa. There they settled in Eastern Africa and gradually spread into the continent, losing diversity as they advanced, and taking up archaic versions as they admixed with older homo lineages in Africa.

Neanderthals, Denisovans, and Humans

Surprisingly, the paper stated that "H. sapiens entered in Eurasia with a set of functional alleles absent in Neandertals and Denisova, and already derived from their ancestral state" so, they were present in modern humans in Asia and absent in our Neanderthal and Denisovan ancestors but, and this is relevant, "Neandertal and Denisova, two archaic hominid populations inhabiting Eurasia, expressed blood groups currently found in sub-Saharans... For two blood group systems, RH and KEL, the Neandertal alleles are almost exclusively found in modern populations from Sub-Saharan Africa" This suggests that the ancestral populations of Neanderthals and Denisovans, that originated in Asia, migrated into Africa, surviving through admixture with hominins inside AFrica. Their variants are now only found in the red blood cells of populations South of the Sahara. Outside of Africa, the larger population that evolved into modern humans mutated into a derived form, absent in both Denisovans and Neanderthals.

---

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

The Diego blood group and the peopling of America

The Diego Blood group system was discovered by chance in 1953. At that time, a woman who lived in Caracas, Venezuela gave birth to her second child. The newborn became ill with hemolytic jaundice which was caused by an incompatibility between baby and mother's blood. The samples were sent fot analysis and the outcome wwas a new private antigen which was named after the baby, Diego (he died shortly after).

Further studies identified two different variants Dia and Dib. The first was found to be quite frequent among Amerindians and some Asian populations but absent among Caucasians, Africans and Australian Aboriginals. The second variant was common around the world.

Dia was also found among Polish people, and it is conjectured that it reached Europe via the Tartar - Mongol invasions in the 1300s.

The two variants arise from a mutation in the SLC4A1 gene. Where an amino acid change provokes Dia. As it is not found in all Asian populations it may have arisen in a confined area of Asia and moved into America with part of these people when they migrated into the New World.

In America there are two variants Di(a-) common in South America and NW North America while the other one D(a+) is found elsewhere. This may be due to the fact that the Di(a-) people are the remnants of a first wave of migrants, later over ran by a Di(a+) population. This theory was proposed by M. Layrisse and J. Wilbert [1] who wrote:

"The Diego blood group is an exclusive Mongoloid gene marker, although it is not present in all Mongoloid populations. The absence of the gene in Waica Indians and its very low frequencies in Warrau and Yaruro Indians of South America suggest that it represents a genetic characteristic of Marginal American Indians. Since Marginal Indians are considered to be early comers to the New World, we suggest that Diego-negative t populations were the first to arrive and to extend throughout South America, while the Diego-positive tribes came later."

Interestingly this theory would be completed by a later third wave that peopled the Arctic region where the Dia type is absent.

A recent paper by Bégat C, Bailly P, Chiaroni J and Mazieres S [2] gives another explanation:

"...For this purpose we assumed that the geographic distribution of the DI*A allele coding for Dia is not random but rather coincided with cultural traits according to the gene-culture comigration concept.
[...]
High frequencies were observed in the Peruvian Andes, on the Guyanese Plateau, in the southeastern Amazonian Basin, in a region comprising the Brazilian state of Pará, and along the Tapajos, Xingu and Araguaia tributaries of the Amazon River. Low frequencies occurred mainly in North America, in Chaco and at southern tip of South America. The DI*A allele was totally absent in the Arctic (Eskimo and Tlingit), Panama Isthmus (Bribri and Teribe), Tierra de Fuego (Alacalufe), and a few pocket areas in North America (Cherokee), Northern Brazil/Southern Venezuela (Ninam and Yanomama), and the Chaco area (Ayoreo, Zamucoan). [2]

They go on to explain that the Ayore suffered from a "severe founder effect", and this may explain the lack of DI*A in them. Then they explain its absence among the Panama Isthmus populatons because these Chibchan-speakers "predecessors have lived in isolation from Central and South Amerindians since the early Holocene" [2].

The Fuegians lack this allele because of "isolation by distance with ensuing drift" [2] and its void in Northern North America is due to a "Secondary migration ... of non-Amerind-speakers, i.e., Eskimo-Aleut and Na-Dene speakers, from Alaska to Greenland and Southwestern North America.", they back-migrated into Siberia too, and that explains the link between their language and the Yeniseian languages in Siberia where the Yeniseian speakers also lack the Di*A allele. Then came even more gene flow carrying the DI*B allelle into the boreal part of the New World.

Frequency

• 5% Chinese
• 12% Japanese
• 54% South American Natives
• 4% North India
• 0.47% Polish
• 0.01% Other Caucasians

I must admit that the Diego blood Group is an oddity, found in many non-African It has an exclusively Amerindian variant the Dia variant but, and this is interesting: An antibody of the Diego antigen, Anti-Di(a), is the cause of hemolytic transfusion reactions and also of hemolytic disease of the newborn (like happened to the baby, Diego). The presence of this antigen, or Dia alloimmunization has been observed among different Asian and South American Amerindian populations. A study by Baleotti et al., (2014) [3] found that:

"...HLA-DRB1*07:01 allele was overrepresented in Dia-alloimmunized patients compared to nonimmunized patients and to healthy donors.
... Individuals carrying the HLA-DRB1*07:01 allele present an increased risk for Dia alloimmunization..."

This means that those with the lowest frequency of this type of HLA, which in the map below would mean those native to the areas shaded in blue or pale blue, would not have the Anti-Di(a) antigen, because they have Di(a). And the map is clear: The Americas and east Asia. But! why is Australia, Melanesia and Africa also blue?

Also the Altai region (i.e. Denisova-land) is blue. Could the Australia -Melanesia - Americas mean some Denisovan introgression? But what about Southern and Western Africa?.

Could this imply some introgression there, in Africa, of an archaic hominin? See my post an ancient Y chromosome lineage, which mentions a possible archaic-human admixture in a Nigerian site known as Iwo Eleru, where human skeletal remains with both archaic and modern features were found and dated to ~13 kya.

The map below shows the global distribution of DRB1*07:01:01:01, (Source).

And this is the image from [2] showing the distribution of the Diego factor in America (black = none, dark blue= high)

I have the impression that Diego factor is archaic, not the result of a bottleneck.

Sources
[1] M. Layrisse, J. Wilbert, Science (1961). Absence of the Diego Antigen, a Genetic Characteristic of Early Immigrants to South America, 13 October 1961, Vol. 134 no. 3485 pp. 1077-1078 DOI: 10.1126/science.134.3485.1077
[2] Bégat C, Bailly P, Chiaroni J, Mazieres S (2015) Revisiting the Diego Blood Group System in Amerindians: Evidence for Gene-Culture Comigration. PLoS ONE 10(7): e0132211. doi:10.1371/journal.pone.0132211
[3] Baleotti, W., Ruiz, M. O., Fabron, A., Castilho, L., Giuliatti, S. and Donadi, E. A. (2014), HLA-DRB1*07:01 allele is primarily associated with the Diego a alloimmunization in a Brazilian population. Transfusion, 54: 2468–2476. doi: 10.1111/trf.12652

---

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