Biology Reference
In-Depth Information
human history. The alternative is that it is a reverse mutation brought about per-
haps by gene conversion templated by a related FMO gene. The biochemical and
toxicological significance of the loss of FMO2 activity in human lung is unclear
and so it is premature to speculate as to whether its loss conferred a selective
advantage upon bearers or whether the inactivating lesion could have become
fixed by genetic drift alone.
6.2.11 Overview
Several genes are thus known to have become inactivated during primate/human
evolution. Inactivation does not however always imply the deletional removal of
the gene. Rather, the once functional gene sequences often remain in the human
genome to be detected as the inactive orthologues of their still active counterparts
in the genomes of lower vertebrates. A variety of subtle lesions are usually respon-
sible for the inactivation e.g. micro-deletions or insertions, or single base-pair
substitutions which create in-frame stop codons, alter the invariant bases at splice
junctions or adversely affect the binding of transcription factors to the promoter
region. The greater the time that has elapsed since the initial inactivation event,
the greater the number of mutations that have accumulated, and therefore the
harder it is to discern the identity of the initial inactivation event. We may only
speculate as to the reasons for the loss of these genes. In some cases, gene loss may
have been neutral with respect to fitness and the null allele would have become
fixed through genetic drift. In the case of the flavin-containing monooxygenase 2
(
FMO2
) gene, Dolphin
et al.
(1998) calculated, assuming a generation time of 15
years and an effective population size of 10 000, that it would have taken some
600 000 years for the Gln472Term mutation to approach fixation. In the case of
other genes lost from the human or primate genomes, some selective advantage,
for example resistance to pathogens may have accrued to bearers of the inactivated
genes, resulting in the more rapid spread of the mutant allele.
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