SCOOTER82a_Livingstone_Frequencies of Hemoglobin Variants ...

there are still many problems and questions concerning
the specific distributions of each trait
and their population dynamics. The major problem
is why there are so many genetic variants,
and this includes the great number found in
some populations but also the great variation
that exists among major geographic areas. This
great variety seems to indicate the recency of
malaria selection in human populations or: at
least since the human species has spread
throughout most of the world. This expansion
occurred much earlier in the Old World and
reached Australia by 30,000 B.C. while the New
World was not occupied until about 15,000 B.C.
Since the New World was first populated via the
Bering Strait, it is unlikely that malaria was
endemic there until after contact with Africa and
the Old World (Dunn 1965). This is reflected in
the almost total absence of red cell variants in
the Amerindians except where they have been
in contact and admixed with Old World immigrants.
(For these frequencies and others to be
discussed, no citations are given; the data can be
found in the table.)
The recency of malaria selection in the Old
World accounts for the differences between the
Southeast Asian peoples and those of the Middle
East, Africa, and India. Hemoglobin E is
found in very high frequencies in much of
Southeast Asia and has diffused westward as far
as Assam in India, while hemoglobin S is common
in Africa, the Middle East, and India. The
border of these two hemoglobin distributions
around Calcutta corresponds to the major ethnic
border in Northern India between Indo­
European speakers to the west and Tibeto­
Burman speakers to the east. It also corresponds
in a general way to the spread of agriculture
and empires from the two principal foci of the
evolution of civilization in the Middle East
and China.
In addition to these two hemoglobin variants,
thalassemia and glucose-6-phosphate dehydrogenase
deficiency are also found in high frequencies
in both major regions, but in contrast
each condition is the result of many different
mutations. This bewildering variety of mutations
in both these areas where malaria has been a
selective factor is markedly different from populations
in more temperate climates to the north
and south of the equator. These latter populations
are almost completely homozygous for the
normal allele at all these loci. Very large samples
have been examined for some of these populations
and many different mutations have been
detected, but these occur at very low frequencies.
For example, the Japanese have never
been subjected to severe malaria and hence are
one of these homozygous populations. However,
the number of Japanese examined for
hemoglobin or G6PD variants now number in
the millions, and a great many rare variants have
been detected. There have been much smaller
samples of Eskimos, Polynesians, Australian
Aborigines, Russians, Swedes, and many other
populations investigated, and it is now rather
conclusive that these populations do not have
polymorphic (>1%) frequencies of hemoglobin
variants or of G6PD deficiency. It may be possible,
however, that with more sophisticated
techniques several variants of G6PD that are not
deficient could be found.
It would seem that as endemic malaria has
spread throughout the world, the hemoglobin
and G6PD deficient mutants that are already
present in very low frequencies in any population
have begun to be selected. As would be
expected, these variants vary from one popula-
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tion to another. Since thalassemia and G6PD
deficiency are detected by "phenotypic" or
functional differences in the gene products,
many different mutations are subsumed in each
of these clinical conditions. Thus the first mutant
encountered by malaria in its diffusion throughout
the world would most likely be a "thalassemic"
or "G6PD deficient" allele rather than a
hemoglobin variant. The somewhat peripheral
distribution of high frequencies of thalassemia
accords with this hypothesis. Thalassemia is
found in most populations in malarious areas
and in high frequencies in some endogamous or
isolated populations in the central areas of the
malarial belt, but some of the highest frequencies
of thalassemia are found on the edges in
Sardinia and Europe, West Africa, China, and
New Guinea. On the other hand, in Africa, from
Nigeria westward through Central Africa to the
East Coast, where hemoglobin S occurs in its
highest frequencies and is apparently close to
equilibrium, there are very low frequencies of
thalassemia, or more specifically ,8-thalassemia.
Hemoglobin S has replaced ,8-thalassemia in
these populations, but in one of the isolated
peoples in this area, the Nilotic tribes which
include the Nuer, Dinka, and Shilluk of the
Sudan, there are very low frequencies of hemoglobin
S and apparently high frequencies of ,8thalassemia.
Also in accord with this hypothesis
of recent hemoglobin S diffusion, this gene has
replaced ,8-thalassemia in the oasesof Saudi Arabia
and is in the process of replacing it in Macedonia,
which appears to be the wave of
advance of this gene.
In the populations of Assam, Thailand, and
Cambodia, where hemoglobin E attains its highest
frequencies, this gene has almost completely
replaced ,8-thalassemia, while out through the