From JIM MACKINTOSH
I was interested to read your article on the causes of schizophrenia,
especially ideas concerning its evolution (‘Understanding the inner voices’,
9 July). I believe this problem, and that of other major mental illnesses,
can be solved by Maynard Smith’s discussion of genetic diversity in The
Theory of Evolution, although in that book the author confined his comments
to populations of captive fruitflies.
Genes are carried on chromosomes which are made of DNA. Most animals
receive one set of chromosomes from their father and one set from their
mother. Thus they have two copies of each gene. Sometimes the two versions
of any one gene in an individual may be the same (this is called homozygous)
or sometimes they may be different (heterozygous). Often, when an animal
gets a different version of a gene from each parent, it does better in an
evolutionary sense. This is called heterosis or heterozygote advantage.
What is sometimes overlooked is that frequently many genes, each located
at a different spot on a chromosome, contribute to any one characteristic
of an individual. This is polygenic inheritance. Thus it is possible that
an individual is homozygous at most or even all of the genes that contribute
to a characteristic. However, the greater the number of versions of each
gene there are in the population the less likely it is this will occur,
since it is unlikely that both parents would carry the same versions. It
is easy to see that the odds decrease even further as the number of genes
that contribute to a characteristic, such as schizophrenia, goes up.
The possibility that schizophrenia may be more common in people who
are homozygous in some or all of these genes would account for the consistency
and rather high frequency of schizophrenia around the world (high, given
that schizophrenics have less children). Secondly, varying patterns of homozygosity
could result in varying degrees of severity, and kinds, of mental illness.
It would also explain why searches for a single schizophrenic gene remain
unsuccessful.
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It is particularly interesting to speculate at what levels the heterozygotic
advantage operates; one can imagine molecular, physiological or psychological/behavioural
reasons, which could act separately or in combination. Concerning behaviour,
for example, it is conceivable that an attenuated level of obsession (although
almost any hallmark of the major mental illnesses can be substituted at
this point) is of advantage to, say, uninspired disinterest, and so on.
Jim Mackintosh New South Wales, Australia
