Chemistry Reference
In-Depth Information
and east. In India, the frequency of lactase persistence is higher in the north than
the south, and in the rest of the world, lactase persistence frequency is generally
low. In Africa, the distribution is patchy, with some pastoralist nomadic tribes
having high frequencies of lactase persistence compared with the neighbouring
groups inhabiting the same country (Bayoumi et al., 1981), with a similar pattern
observed between Bedouin and neighbouring populations in the Middle East
(Cook and al-Torki, 1975; Snook et al., 1976; Hijazi et al., 1983; Dissanyake et al.,
1990).
The noted correlation of lactase persistence phenotype with the cultural
practice of milking engendered the hypothesis that this trait has been subject
to strong positive selection.
6.6.
Identifying the Causes of Lactase Persistence
As discussed above, many research groups (Sebastio et al., 1989; Buller et al.,
1990; Lacey et al., 1994; Pie et al., 2004) reported lactase activity in the
intestine of young and suckling mammals, but not in the intestine of the
corresponding adult of the species, which provided further evidence that the
ancestral state for mammals (and therefore humans) is for lactase expression
to be down-regulated following the weaning period.
Many enzymes are regulated via an inducible system whereby expres-
sion of an enzyme is activated or increased if the concentration of its substrate
is high, for example, the lac operon in Escherichia coli is an inducible system in
which
-galactosidase is expressed only in the presence of lactose (Jacob and
Monod, 1961). Initially, an inducible system was hypothesised to regulate
lactase expression in humans (Gilat, 1971; Cook, 1988), and would indeed
provide a neat explanation of why lactase is down-regulated following wean-
ing and why lactase persistence is seen more commonly in populations where
milk forms an integral part of the diet. However, many animal studies have
shown no increase in lactase activity in response to prolonged exposure to
lactose (Plimmer, 1906; Leichter, 1973; Gutierrez et al., 2002), and studies in
human populations confirm this: a study of 50 adult Thai individuals who
voluntarily ingested daily lactose doses for 1 month reported no improvement
in lactose absorption or increased lactase activity, thus demonstrating that
the enzyme is not inducible (Keusch et al., 1969).
By the early 1970s, it had been established using family studies that the
lactase persistence polymorphism in humans had a genetic cause, and was
inherited in an autosomal dominant manner (Ferguson and Maxwell, 1967;
Sahi, 1974). In another study, monozygotic twins showed 100% concordance
of lactase persistence phenotype, and phenotype frequencies in dizygotic
twins were found to agree with expectations of an autosomal dominant
