EVOLUTION has moulded living creaturesin such a manner that their abilityto survive an reproduce is constantlyimproving. on a rough sense, onemay say that given two populations,one of ancestors and a second ofdescendants, the descendants will carrya subset of ancestral genes: genes whichcontribute to a higher fitness are morelikely to persist and spread than thosegenes that are relatively less capable ofdoing so.
Renowned biologist J B S Haldanehad said more than forty years agothat the course of evolution has beenmoulded to a large extent by disease anddisease-causing organisms. A con-temporary look at Haldane's thesisfrom the specific angle of malaria is thesubject of a recent article by G Pasvol ofthe Imperial College School of Medi-cine, UK (The Lancet, Vol 348, No 903 1).
Because the signature of evolutionarychange is a change in the genetic make-up of organisms, the first thing to ask is, are there genes that look as if they haveevolved in the course of the fight againstmalaria? It appears that there may betwo such sets, both recognised by thediseases they can lead to. One disease isknown as sickle cell anemia and theother, thalassemia. Both are due tochanges in the sequence of the DNA thatcodes for haemoglobin, the protein thattransports oxygen to the tissues. Notethe seeming paradox: the geneticchanges that we are talking about areboth helpful (if they help us counteractmalaria, that is) and harmful (becausethey demonstrably also cause disease).The sickle cell part of the story is reasonably well understood.
There is a variant version, or allele,of the normal ('A') haemoglobin geneand it is known as the s allele.Individuals with two copies of the sallele suffer from severe anaemia, butthose with one copy of s and one copy ofA are resistant to malaria whereas thosewith two copies of A are not. The basis ofthe resistance can vary. The s allele canaffect the entry of malarial parasites intored cells, or the development of parasites within infected cells, or cause theremoval of infected cells from the system, or all three. Therefore, it persists in the population by virtue of its presence.SS combinations, meaning individualssuffering from sickle cell anaemia, areborn in every generation. As one mightexpect on the basis of this correlation,the s allele tends to be found in thoseparts of the world that have had a historyof malarial infection.
The thalassemia story is not as clear. What is becomingevident, though, is that thalassemia has affected humangenes in a big way. An intriguing finding that has emerged recently is that individuals withalpha thalassemia have higherrisks of clinical malaria (invasion of red cells by the parasite) than others, a paradoxical finding if the gene is supposed to offer protection. The suggestion made by Pasvol and co-workers is that such clinicalinfection might act as a livenatural vaccine and hasten theacquisition of immunity from the disease itself. Unfortunately, it is not easy to prove this hypothesis because as of today there is no clear-cut laboratory method of demonstrating immunity against malaria.