Biology Reference
In-Depth Information
In human history, demographic expansions have often occurred as a result of
technological developments affecting food availability and transportation fuelled
by the pursuit of military or economic objectives. In terms of establishing genetic
differences between populations, linguistic barriers have also been important
(Cavalli-Sforza 1997).
2.3.7 The action of natural selection in human populations
From the time when the ancestral man first walked erect, with hands freed
from any active part in locomotion, and when his brain-power became suffi-
cient to cause him to use his hands in making weapons and tools, houses and
clothing, to use fire for cooking, and to plant seeds or roots to supply himself
with stores of food, the power of natural selection would cease to act in pro-
ducing modifications of his body, but would continuously advance his mind
through the development of its organ, the brain.
Alfred Russel Wallace
Darwinism
(1889)
Evidence for the recent effects of natural selection on human populations comes
indirectly from observed variation in allele frequencies (Cavalli-Sforza
et al
.,
1994) with infectious disease often serving as the selecting agent (Hill 1996a;
1996b; Levin
et al
., 1999). The classical example of pathogen-driven selection is
the heterozygote advantage accruing to carriers of the Glu6
Val sickle cell muta-
tion in the
-globin (
HBB
) gene which confers resistance to
Falciparum
malaria
(Vogel and Motulsky, 1997). It has been suggested that the high frequency of cer-
tain diseases in specific populations may be explained in similar ways (Motulsky
1995; Zlotogora 1994).
Heterozygote advantage has been invoked to account for the spread of the com-
mon cystic fibrosis mutation (
F508) in the
CFTR
(7q31.3) gene in Caucasian
populations. The basis for heterozygote advantage was proposed to be increased
fitness of heterozygous carriers during cholera epidemics (Gabriel
et al
., 1994).
However, it is difficult to see how such overdominant selection could have
brought about the extremely high prevalence of one specific
CFTR
lesion (
F508)
relative to the large number of alternative
CFTR
mutations known. It would also
be difficult to explain the gradient in
F508 frequency across Europe unless there
was also a gradient of selective pressure. Thus, the most parsimonious explana-
tion is probably genetic drift.
A large body of data has accumulated on HLA polymorphism and its relation-
ship to disease susceptibility, resistance and progression (Bodmer, 1996; Hall and
Bowness, 1996). Polymorphic alleles at both HLA class I and II loci have been
shown to be under selection (Begovich
et al
., 1992; Hill
et al
., 1991; Hughes 1988,
1989). One recent example is selection for specific HLA class II (
HLA-DR
and
HLA-DQB
; 6p21.3) alleles as a result of hepatitis B virus infection (Thursz
et al
.,
1997). More than 90% of the 135 known
HLA-DRB1
alleles appear to have been
generated since the divergence of human and chimpanzee (Bergström
et al
.,
1998); such changes appear to have arisen both by point mutation and by gene
conversion and are consistent with the existence of substantial selective pressure.
Pathogen-driven selection may also have been responsible for increasing the fre-
quency of genetic variants at other loci, for example the
CCR2
(3p21; Smith
et al
.,
