Biology Reference
In-Depth Information
and Levitan, 1983). How did this unusual polymorphism evolve and become
established in the general population? Winter
et al
. (1995) noted that the sequence
flanking the L allele contained numerous homologous motifs suggestive of an
ancient duplication event. Some residual homology was also noted between the L
and S alleles (
Figure 5.4
) but the L allele did not obviously contain duplicated
sequence. The most parsimonious explanation was therefore the emergence of the
S allele from the L allele by partial deletion followed by sequence divergence. The
deletion event(s) could have occurred by homologous recombination mediated by
the homologies between the L-specific sequence and the region immediately
downstream. Interestingly, however, no difference in expression could be dis-
cerned between the two alternative alleles (Winter
et al
., 1995).
A repeat length polymorphism in the human solute carrier family member
SLC6A4
(17q11.1-q12; Delbrück
et al
., 1997) gene also appears to be present in
the gorilla although not in the chimpanzee. It is unclear whether this is an exam-
ple of an ancient trans-species polymorphism (Chapter 1, section 1.2.2) or
whether it has arisen independently in the two lineages.
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CTGATTTAGTTAACGAGAAACAAAAAATCCTGCAGACAAGTTTC TCCTCAGTCAGGTA
T A AAC CAAGTTT TCTT GT AG
TGGGTATGAAC CAAGTTTGTTTCCTTGGTTAG
-304
Figure 5.4.
Alignment of the alternative L- and S-specific sequences in the promoter
region of the human
AT3
gene indicating regions of homology (redrawn from Winter
et
al
., 1995). For explanation, see text.
L
S
Ancestral locus
APOE
APOC1
APOC4 APOC2
HCR
5kb
~10kb duplication
APOE
APOC1
APOC1P1
APOC4 APOC2
HCR-1
HCR-2
Present human locus
Figure 5.5.
Evolution of the human apolipoprotein E2/CI/CIV/CII loci (adapted from
Allan
et al
., 1995). The relative locations of the human
APOE
,
APOC1
,
APOC2,
and
APOC4
genes and the
APOC1P1
pseudogene are shown by closed boxes. The locations
of the two hepatic control regions (HCR) are denoted by ovals.
