EVOLUTION OF THE HUMAN
ABO BLOOD GROUP SYSTEM
Bonnie B. Glass
BY-590 Dr. McCall
Spring 2001
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The purpose of this web page is to explain some basic facts about human ABO blood group system and to summarize the research and hypotheses regarding its evolution.

BACKGROUND
The ABO System -- A Polymorphism

(http://www.bayerpharma-na.com/children/RON/circu/chrc.0103.asp)
Humans can have blood types A, B, AB, or O. This is known as the ABO blood group system, and it is a polymorphism. A polymorphism is defined as a "genetic locus with two or more alleles that occur in appreciable (>1%) frequency in a given population" (http://www.as.ua.edu). The ABO blood group system was the first polymorphism discovered in humans. It is however only one of MANY systems involving the red blood cells.
Antibodies and Antigens
Understanding the difference between antibodies and antigens is essential to understanding the ABO blood group system and its evolution. Antibodies are substances produced by the body when it is invaded and act to protest it from the foreign substance. Antigens are found in the invading substance and elicit the production of antibodies. The two substances, thus, work in conjunction with each other.

(http://www.uen.org/utahlink/activities/view activity.cgi?activity ld=3037)
Typically, the body does not produce antibodies until AFTER it has been introduced to a new substance. The blood group antigens, on the other hand, are produced during the development of the circulatory system of the fetus.
Because these antibodies are present, blood of certain types will be incompatible. Before this was understood, death was often the result in transfusions and transplants.
This transfusion dilemma led Karl Landsteiner (pictured below) to

(http://daphne.palomar.edu/blood/ABO system.htm)
discover the ABO system in 1900. Interestingly, he used blood samples from his fellow lab staff. Fortunately for him, all blood types were represented so his system remains in use today.
Landsteiner's ABO System
In this blood group system, A and B are codominant thus humans may have the following phenotypes and genotypes and the corresponding antibodies and antigens.
Phenotype Genotype Antigens Antibodies
A
AA, AO
A
B
B
BB, BO
B
A
O
OO
None
A, B
AB
AB
A, B
None
Since Landsteiner's discovery, hundreds of specificities in human blood types have been determined (Socha et al., 1984). The ABO blood group system remains the most widely used.
To learn more about your blood, check out this interesting site by clicking here.
WHY STUDY THE EVOLUTION OF HUMAN BLOOD TYPES??
There are several reasons scientists are interested in studying the evolution of human blood types -- the predominant reason being it helps them to understand the place humans occupy in evolution's branching tree. In other words, by studying the similarities and differences between human and non-human primate blood groups scientists can determine who our closest common ancestors are and the degree of our relationship.

What Distinguishes A, B, and O blood types from each other?
The type of blood a person has is determined by alleles at a single locus at chromosome 9 (Martinko et al., 1993). These alleles encode for different amino acids called glycotransferases.
In order to be blood type A, cytosine at nucleotide site 793 translates to leucine 265 and guanine at nucleotide site 800 transloates to glycine 267.
In order to be blood type B, the cytosine at 793 translates to methionone 265 and the guanine at 800 to alanine 267 (Martinko et al., 1993).
Blood type AB occurs when both changes occur.
Blood type O is caused when an inactive or nonfunctional protein is coded for.
Martinko et al. (1993) remarked regarding these changes that it is "surprising that they have such a great effect on the A and B transferases" because the amino acids do not differ greatly from each other.
What About the Blood Types of Other Primates?
The ABO polymorphism exists in many primate species other than just humans and in all anthropoid primates (Diamond, 1997). Blood groups of primates have been studied since 1911 when Dungern and Hirszfeld found an A antigen on chimpanzee red cells (Socha et al., 1984). According to Socha et al., (1984), early studies indicated "striking similarities" between the A-B-O antigens of man and those of anthropoid apes. It was not until the 1960's that research methods improved enough to learn that many similarities existed between human and non-human primates as well as some subtle differences. In their 1984 study, Socha et al. stated that the two groups were "intimately serologically related."
Because of similarities in the immunological responses between human and non-human primates, the same techniques used for testing human blood were used for other primate species.
Scientists have studied certain primate species in much greater depth than others. As a result, we do not know equally about the blood groups of all primates. In the following sections, some of the most researched groups will be explained.


CHIMPANZEES

Of the Old World monkeys, the chimpanzee has been the most studied (Socha et al., 1984). Interestingly, they have predominantly blood type A and in rare cases blood type O, but NEVER blood type B (Socha et al., 1984). Most blood systems found in chimpanzees also exist in man, but there are some species specific characteristics. The chimpanzee is thought to be the ancestor of Cro-magnon man.
To learn more about chimpanzees click here.
GORILLAS
In contrast to chimpanzees, gorillas have been found to possess ONLY blood type B. Some evolutionary scientists believe the gorilla to be the ancestor of Neanderthal man.
To learn more about gorillas, click here.
BABOONS
Baboons, on the other hand, have been found to possess A, B, and O blood types. The hominoids, humans and the great apes, express the ABO antigens on red blood cells, but baboons do not. In baboons, the antigens were found in other tissue cells. Although the similarity in alleles exist in baboons and humans, the mutations which are in human O alleles are not found in baboon O alleles. This suggests a different origin for the O blood types in each species (Diamond et al., 1997). Unlike humans who have a large percentage of O, in baboons O has arisen several times but remains relatively rare. This suggests a possible selection working against type O in baboons.

Humans, baboons and orangutans have maintained their polymorphism. Because of the absence of B from chimpanzees and O and A from gorillas, the locus determining this phenotype must no longer be under strong selection pressure in the hominoids.
To explore a great web site which explains the differences between the evolutionary history of chimpanzees, gorillas and man, click here.
SO WHAT DOES ALL THIS MEAN?
Scientists have determined by using average mutation rate and considering the required mutations that the divergence of A and B (at nucleotides 793 and 800) must have occurred before humans, chimps, and gorillas had separated and likely before orangutans broke off. Thus A and B diverged at least 13 million years ago (Martin, 1990). In chimps and gorillas, the A and B allele seem to be fixed (Martinko, 1993). Some sources state that the two types are likely of separate origin (http://aol.com/ikaulins/expak), but that they are the original types, not O.
Other evidence used to trace man's evolutionary ancestors to these non-human primates is the MN blood system. Man is M and N; whereas chimps are anti-N and gorillas are anti-M. O is not the original blood type as was previously thought (http://members.aol.com/ikaulins/expak).

IS SELECTION AT WORK TODAY?
If these blood groups are being selected against, the agent is not restricted to humans because the system has been around for over 13 million years. There is only indirect evidence for the possibility of natural selection in the evolutionary pattern of ABO groups (Saitou and ). To link natural selection to the frequency of A, B, O phenotypic frequency requires more evidence. One such study was completed by Boren et al. (1993), in which a bacterium casing gastric disorders was linked to blood type (Saitou ). The researchers found there to be less receptors for the bacterium in blood types A and B, thus people with blood type O were more susceptible. If more blood types could be linked to microorganisms, there would be more evidence for natural selection.
Several question remain. For example, if natural antibodies help to protect the body against parasites, then why is O, which has both A and B, antibodies not at an advantage? Also, O is a nonfunctional allele, yet it is quite common in certain areas like South America where it is fixed in the population. This seems to contradict standard mutation drift selection which does not favor nonfunctional alleles (Nazzareno et al., 1995).
To learn more about the world distribution of blood types, click here.

There is also a question as to whether selection is at work today in the interacions between mother and fetus. Some studies have concluded that in mothers with type A blood who are carrying a fetus of type O (and vice versa), there is incompatibility which will result in the spontaneous abortion of the fetus.
In summary, it appears that humans, chimpanzees, and gorilla (and likely ornagutan) followed the same evolutionary origin when comparing their blood types. Because the A and O exist in chimps this is likely the ancestral form of these types found in humans today. The B type found in gorillas today was likely ancestral form found in humans. Thus,