Biology Reference
In-Depth Information
Intriguingly, Miyata
et al
. (1994) have claimed that the rate of evolutionary change
of tissue-specific genes varies with the site of expression. Thus, brain-specific
genes were reported to evolve at a slower rate than immune system-specific genes.
However, since the identity of the compared genes was not revealed and the sam-
ple size small, it is hard to comment on the validity or otherwise of the authors'
conclusions.
7.1.4 Mutation rates and their evolution
The fundamental importance of mutation for any account of evolution is clear.
It enables us to escape from the impasse of the pure line. Selection within a
pure line will only be ineffective until a mutation arises.
J.B.S. Haldane
The Causes of Evolution
(1932)
Although very much dependent upon the type of mutation being considered and
the identity of the gene in question, studies of disease pathology have suggested
that the mutation rate in males is higher than that in females (reviewed by Cooper
and Krawczak, 1993). This has been held to reflect the rather higher number of
cell divisions required from zygote to mature germ cell in the male as compared
to the female. In an evolutionary context, Miyata
et al
. (1987) developed a method
for estimating the male-to-female ratio of mutation rates (
α
m
) from rates of
nucleotide substitution in sex-linked and autosomal sequences. They predicted
that if
α
m
were very large, the rate of synonymous substitution in X-linked genes
would be ~2/3 of that in autosomal genes on the basis that the X chromosome is
twice as likely to be present in a female as in a male. This prediction was borne out
by their analysis of human and rodent gene sequences. Further, the rate at which
the Y chromosome accumulated substitutions was found to be twice that of the
autosomes (the Y chromosome mutates at relative rate
α
m
as mutation always
occurs in a male). The comparison of rodent
Ube1
genes and pseudogenes allowed
α
m
to be estimated to be of the order of 2.0 (Chang and Li, 1995). Similarly, com-
parison of
SMCX
/
SMCY
(Xp11.21-p11.22/Yq) genes from mouse, horse and
human yielded an estimate for
α
m
of 3.0 (Agulnik
et al
., 1997). By contrast, com-
parison of intronic sequences of the homologous
ZFX
(Xp21.3-p22.3) and
ZFY
(Yp11.32) loci in humans, orangutans, baboons and squirrel monkeys suggested
that
m
may be as high as 6.0 in primates (Shimmin
et al
., 1993). The actual value
of
m
may however be very much dependent upon the species compared. Thus,
-
globin pseudogene sequence data were used to derive estimates of
α
m
between 3
and 6 in higher primates but only ~2 in mice and rats (Li
et al
., 1996). If studies
of many different systems indicate that the mutation rate is consistently higher in
males than in females, then it may indeed be possible to view evolution as being
'male-driven' (Hurst and Ellegren, 1998).
That some sequences are hypermutable in the human genome is clear from
studies of pathological lesions responsible for human genetic disease (Cooper and
Krawczak, 1993; Krawczak
et al
., 1998). Hotspots for somatic mutation are also
apparent from studies of mammalian immunoglobulin genes (consensus
sequences, G C/T A/T and TAA; Rogozin and Kolchanov, 1992). Such hotspots
can be interpreted in terms of nearest neighbor effects on nucleotide substitution
rates (Krawczak
et al
., 1998; Section 7.5.1). In an evolutionary context, these
