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Evolution and respiratory genetics

School of Paediatrics and Child Health, Princess Margaret Hospital for Children, Perth, Australia.

CORRESPONDENCE: P. N. Le Souëf, School of Paediatrics and Child Health, Princess Margaret Hospital for Children, GPO Box D184, Perth WA, Australia 6001. Fax: 61 893002097. E-mail: plesouef{at}cyllene.uwa.edu.au

Keywords: Asthma genetics, evolution, parasites, T-helper 2 responses

Received: July 3, 2006
Accepted July 20, 2006

Evolution is a plausible explanation for between-population differences in particular allele frequencies if: the genes involved have related functions; the heterogeneous alleles involved have similar functional consequences; the involved genes are not linked chromosomally; and the patterns observed would result in a biologically plausible, survival-enhancing gene–environment interaction. However, possible evolutionary effects have to be differentiated from founder effects and random genetic drift.

The current authors have noted the existence of a consistent pattern of allelic frequencies in genes related to T-helper 2 (Th2) immune responses in humans of different ancestral backgrounds, residing in climatically similar regions. Th2 responses are thought to have evolved in mammals to resist infection by parasites, particularly helminths. Modern man arose in tropical Africa where helminths thrived. Relatively recently, humans migrated to cooler or drier climates where most helminths struggled to reproduce. The genetic tendency to strong Th2 responses may have become a health liability, the reduction in risk from parasites being counterbalanced by an increased inherited propensity to atopic or allergic diseases.

The pattern noted by the present authors includes specific alleles of interleukin-4 and its receptor, interleukin-13, interleukin-10, the ß chain of the high-affinity receptor for immunoglobulin E, the ß₁-adrenergic receptor, and the alpha chain of tumour necrosis factor. These population-specific polymorphism profiles are likely to be relevant in current disease patterns. The high incidence of asthma in migrants from tropical locations to affluent temperate countries is likely to be related to these patterns. Of even more concern is the possibility that increasing westernisation among the 2 billion people living in the tropics will produce rapidly increasing levels of asthma, as these populations have a high genetic predisposition to allergic disease.

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