Biology Reference
In-Depth Information
8.2.4 Microdeletions in vertebrate evolution
The comparison of gene/protein sequences between humans and the great apes
also yields examples of
in-frame
microdeletions that must have occurred during
primate evolution. Thus, amino acid residue Glu9 of the blue cone pigment pro-
tein (
BCP
; 7q31-q35) present in the talapoin monkey
Miopithecus talapoin
(an Old
World primate) and in the marmoset
Callithrix jacchus
(a New World primate) is
absent from the human protein and appears to have been deleted from the
BCP
gene within the human lineage (Hunt
et al
., 1995). The functional consequences
of the removal of this amino acid residue are however unclear.
Some gene regions harbor a disproportionate number of deletions/insertions
inferred from alignment gaps noted in sequence comparisons e.g. exons 6 of the
orthologous amelogenin (
AMELX
, Xp22.1-p22.31;
AMELY
, Yp11.2) genes of
various vertebrates. These lesions have dramatically reduced the similarity
between vertebrate amelogenins in the Pro/Gln-rich region of the protein as com-
pared with that manifested by other regions (Toyosawa
et al
., 1998).
Some microdeletions occurring during evolution may have been advantageous
by virtue of their alteration of a protein product, others through a change in the
reading frame bringing about gene inactivation (see Chapter 6, section 6.2). Of
course, micro-deletions need not necessarily have conferred any selective advan-
tage; even if merely neutral with respect to fitness, they could have become fixed
by genetic drift alone.
8.3 Microinsertions in evolution
Microinsertions that have occurred during evolution have scarcely been studied.
However, the underlying generative mechanisms are likely to be broadly similar
to those causing human genetic disease. In their study of microinsertions in
human genes causing inherited disease, Cooper and Krawczak (1991) concluded
that insertional mutation involving the introduction of <10 bp DNA sequence
into a gene coding region was not a random process and appeared to be highly
dependent upon the local DNA sequence context. Further, mechanistic models
which have explanatory value in the context of gene deletions were found to be
useful in accounting for the nature and location of gene insertions.
In noncoding DNA, insertions are about half as frequent as deletions and
mostly involve single nucleotides (De Jong and Ryden, 1981; Graur
et al
., 1989;
Saitou and Ueda, 1994). The rate of gap formation, regardless of whether caused
by insertions or deletions, has been estimated to be ~0.15-0.17 kb
-1
Myrs
-1
(Saitou
and Ueda, 1994). In practice, studies of the DNA sequence environment of
microinsertions that have occurred during evolution are likely to be rather diffi-
cult since the original sequence context of the insertion or deletion will often have
become obscured by subsequent mutation.
8.3.1 Gene coding region microinsertions
Microinsertions occurring during human gene evolution can be found by
sequence comparison of either orthologous or paralogous genes/proteins. Thus,
