Type O is not the oldest human blood type, despite being the most common worldwide and despite a persistent folk belief that it represents our species’ original state. The genetic evidence points in the opposite direction: the A allele appears to be ancestral, and the ABO polymorphism itself has been maintained across primate species for at least 20 million years. Type O is a relatively recent modification, the product of mutations that disabled a functional gene rather than a primordial starting condition.
Where the Myth Comes From
The idea that Type O is the “original” blood type has a satisfying logic to it. O is defined by the absence of both A and B sugar molecules on red blood cells, so it feels like a blank slate from which the other types might have evolved. It is also the most common blood type globally, which reinforces the intuition that it must be the default. Some popular accounts of evolutionary dieting and blood-type personality theories have amplified this assumption, treating O as the “hunter-gatherer” blood type and A and B as later arrivals linked to agriculture and nomadism. None of that is supported by molecular evidence.
The real story is essentially the reverse. The ABO gene encodes an enzyme that attaches specific sugar molecules to proteins on the surface of red blood cells. The A and B versions of the gene each produce a working enzyme that adds a slightly different sugar. The O version produces no working enzyme at all. It is a broken copy, carrying a deletion that knocks the gene out of commission. In evolutionary terms, “having a functional gene” almost always predates “having a broken version of that gene,” and the ABO locus is no exception.
A and B Are Far Older Than O
The most striking evidence that O is not the ancestral type comes from comparisons across primate species. Humans, chimpanzees, gorillas, gibbons, and Old World monkeys all carry versions of the ABO gene, and the A and B variants found in these species are not independent inventions. Genetic analysis has shown that the key mutations distinguishing A from B occurred before the lineages leading to humans, chimps, gorillas, and orangutans split apart, making the A/B polymorphism at least 13 million years old.1PubMed. Primate ABO glycosyltransferases: evidence for trans-species evolution Other analyses push this figure even further back, estimating that the same ABO genetic variants have persisted under balancing selection for roughly 20 million years.2PubMed Central. Ancestry runs deeper than blood: the evolutionary history of ABO points to cryptic variation of functional importance
This phenomenon, in which different species share the same alleles not because they evolved them independently but because they inherited them from a common ancestor, is called a trans-species polymorphism. At the ABO locus it is remarkably well documented: genetic variation data in humans, gibbons, and Old World monkeys are inconsistent with a model of convergent evolution and instead support the idea that A and B alleles are shared by descent among species that diverged tens of millions of years ago.3PubMed Central. The ABO blood group is a trans-species polymorphism in primates Outside of immune system genes, this kind of long-term balanced polymorphism is essentially unique among hominoids and Old World monkeys.
The O allele, by contrast, is a human-lineage event. Phylogenetic analysis of O alleles suggests that the most common silencing mutation, a single deleted nucleotide in the gene’s coding region, appeared once in human evolution and that the diversification of the three major human ABO lineages (A, B, and O) dates to roughly 4.5 to 6 million years ago.4Transfusion. Evolution of the O alleles of the human ABO blood group gene That is a substantial age in human terms but young compared to the A/B divergence. To put it plainly, the A and B enzymes were already ancient when the O mutation first appeared in our lineage.
Neanderthals and Denisovans Had Type O Too
If you sequenced the DNA of our closest extinct relatives hoping to find the “original” blood type, you would find a mix. Genomic data from four archaic individuals, three Neanderthals and one Denisovan, show that they were polymorphic for ABO, carrying both O alleles and functional alleles.5PubMed Central. Blood groups of Neandertals and Denisova decrypted The Denisovan individual carried two different forms of O. The Altai Neanderthal was homozygous for a rare O2 variant, while the Chagyrskaya and Vindija Neanderthals were each heterozygous, carrying one O allele alongside a different allele. The Vindija Neanderthal even carried a functional allele resembling a rare modern human variant.6Molecular Biology and Evolution. ABO Genetic Variation in Neanderthals and Denisovans
What this tells us is that the O allele was already circulating in the hominin lineage hundreds of thousands of years ago, well before modern humans left Africa, and that archaic hominins shared blood group alleles still found in living sub-Saharan African populations. But it does not make O primordial. Neanderthals and Denisovans also carried functional A-like and B-like alleles. The O allele in archaic hominins, like the O allele in us, arose from mutations that inactivated a gene that was already there and already doing something.
Why Type O Became So Common
If O is a broken gene, why did it spread so widely? In most cases, losing a gene’s function is harmful, but the ABO locus is unusual because losing A or B surface sugars can be advantageous when certain pathogens are around. The best-studied example involves malaria. In a study of children in a malaria-endemic region, blood group O was associated with a roughly two-thirds reduction in the odds of developing severe malaria compared to non-O blood groups, an effect linked to reduced rosetting, a process in which infected red blood cells clump with uninfected ones and worsen the disease.7PubMed Central. Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting Structural work has confirmed that the ABO blood group dependence of rosetting has a physical basis: the malaria parasite’s surface protein binds more readily to A and B sugars than to the unmodified sugars on O cells.8PLOS Pathogens. Structural Basis for the ABO Blood-Group Dependence of Plasmodium falciparum Rosetting
This malaria advantage is strong enough that it could drive the O allele to high frequency in tropical and subtropical regions where falciparum malaria has historically been intense. Anthropological surveys have long noted that the geographic distribution of blood groups broadly mirrors historical exposure to infectious diseases, including malaria, cholera, and plague.9PubMed. Relationship between infectious diseases and human blood type The O allele likely rose in frequency not because it was the starting point but because it conferred a survival advantage in disease-rich environments.
The Cholera Problem
The relationship between blood type and disease is not one-directional, and this is part of what keeps A and B alleles in the population rather than letting O sweep to fixation everywhere. People with blood group O appear to be more susceptible to severe cholera. In a study from an endemic area in Bangladesh, household contacts with blood group O were roughly twice as likely to develop severe illness if infected with the cholera bacterium compared to people with other blood types.10PubMed Central. Blood group, immunity, and risk of infection with Vibrio cholerae in an area of endemicity
This sets up what evolutionary biologists call a trade-off. In a region with heavy malaria pressure, the O allele has a clear advantage. In a region with endemic cholera but little malaria, being type O might actually be dangerous. Wherever both diseases circulate, neither O nor non-O has a clean win. These opposing pressures help explain why all three major alleles have persisted for so long rather than one of them replacing the others. The same basic dynamic, different pathogens favoring different blood types, likely played out with other infectious diseases across human history, though the evidence for some proposed associations, like smallpox, has been mixed. A hospital-based study in Madras found no clear link between ABO blood group and either the frequency or severity of smallpox.11PubMed Central. Smallpox frequency and severity in relation to A, B and O blood groups
Native Americans and the Founder Effect
One of the more dramatic patterns in global blood-type distribution is that the vast majority of Native Americans are type O.12PubMed. Blood group O alleles in Native Americans: implications in the peopling of the Americas In some indigenous populations, O approaches 100%. This has sometimes been misinterpreted as evidence that O must be the oldest type, on the reasoning that the first Americans carried an “original” blood type and that A and B arrived later with European colonizers. The actual explanation is more mundane and involves population bottlenecks.
When the ancestors of Native Americans crossed from Siberia into the Americas, they did so as relatively small groups. Small founding populations do not carry the full range of genetic diversity found in their parent population. If the founding group happened to have high O frequencies and low A and B frequencies, the Americas would start with that skewed distribution, and genetic drift in small, isolated populations would push O even higher. Ancient DNA from pre-Columbian remains supports this explanation: analysis of 31 individuals from highland Peru found that all carried O alleles, predominantly the O02 variant, with no significant difference from modern Native American populations but a clear difference from Siberian populations.13PubMed. Molecular characterization of ABO blood group frequencies in pre-Columbian Peruvian highlanders Similarly, ABO genotyping of pre-contact individuals from eastern North America found frequencies consistent with modern Native Americans and inconsistent with Siberian populations, supporting a founder effect during the initial settlement of the continent.14PubMed. An ancient DNA test of a founder effect in Native American ABO blood group frequencies
The near-fixation of type O in the Americas is not a window into deep human ancestry. It is a snapshot of what happens when a small population splits off and carries only part of the original genetic toolkit with it.
Type O and the Clotting Trade-Off
Blood type does not just matter for transfusions and infectious disease. ABO status has a measurable effect on blood clotting, specifically on levels of von Willebrand factor, a protein that helps platelets stick together to form clots. People with type O have the lowest average levels of this protein, roughly 25 to 30% lower than people with other blood types.15IntechOpen. Blood Group Antigens as Disease Markers: Infectious, Autoimmune and Neoplastic Associations In one study, the mean value for group O individuals was about 75 units per deciliter, compared to 106 for group A, 117 for group B, and 123 for group AB.16PubMed. The effect of ABO blood group on the diagnosis of von Willebrand disease
This difference cuts both ways. Lower von Willebrand factor means that people with type O have a reduced risk of venous blood clots, which is genuinely protective against conditions like deep vein thrombosis and pulmonary embolism.17Haematologica. The relationship between ABO groups and subgroups, factor VIII and von Willebrand factor But it also means they bleed more easily. Type O is dramatically overrepresented among people diagnosed with Type 1 von Willebrand disease, the most common inherited bleeding disorder. The same study that measured clotting factor levels found that 77% of the 114 patients diagnosed with this condition were type O, compared to about 45% in the general population.16PubMed. The effect of ABO blood group on the diagnosis of von Willebrand disease This is another dimension of the evolutionary balancing act: the O allele protects against clotting disorders while increasing vulnerability to bleeding.
Blood Type and the Gut
ABO blood group antigens are not confined to red blood cells. In people who carry a functional copy of a gene called FUT2, these same sugar molecules are expressed on the lining of the gastrointestinal tract and in body secretions like saliva. This means your blood type potentially shapes which bacteria can colonize your gut, because different microbes have different preferences for the sugar structures they latch onto.
Research comparing the gut microbiomes of healthy people with different blood types has found that being a secretor (someone who expresses blood group sugars in their gut) is associated with less microbial diversity at higher levels of classification, and that having blood group A antigens in particular is linked to expansion of certain bacterial families.18PubMed Central. Relationships between gastrointestinal microbiota and blood group antigens The field is still young and the sample sizes in early studies have been small, but the implication is that ABO blood type may influence health in ways that go well beyond red blood cells and transfusion compatibility. If pathogens in the gut interact differently with A, B, and O sugars, that adds yet another layer of selection pressure keeping multiple alleles in play.
Other Blood Group Systems Shaped by Infection
ABO gets most of the public attention, but humans have dozens of blood group systems, and several of them show even more dramatic evidence of natural selection. The Duffy system is a striking case. People who lack both Duffy antigens on their red blood cells, a phenotype that is nearly universal in sub-Saharan Africa, are resistant to infection by the malaria parasite Plasmodium vivax, which needs at least one Duffy antigen to invade red blood cells.19PubMed Central. Duffy Blood Group System and the malaria adaptation process in humans The mutation that eliminates Duffy antigen expression swept to near-fixation in Africa with a selection coefficient among the strongest ever estimated in the human genome, rising from very low initial frequency to dominance in roughly 42,000 years.20PLOS Genetics. Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans
The Rh system is another ancient blood group with deep primate roots. Sequence analysis of Rh genes across primates, from humans to marmosets, reveals a high degree of conservation, and phylogenetic reconstruction suggests that the Rh genes of African great apes are more closely related to the human RhD gene than to the human RhCE gene, reflecting an evolutionary divergence that predates the human-ape split.21PubMed. Structural analysis of the RH-like blood group gene products in nonhuman primates The distribution of the Rh-negative phenotype in modern humans, concentrated in Europe and Central Asia, is best explained by founder effects rather than by any single pathogen-driven selection event.22PubMed. The relationship between blood groups and disease
These parallel stories across different blood group systems reinforce the same lesson visible in ABO: blood types are not static labels inherited unchanged from a single ancestral state. They are moving targets, shaped by mutation, drift, migration, and above all by the pathogens that have been trying to get into our cells for millions of years. The O allele is one chapter of that story, but it is a relatively recent chapter, not the first page.