Biology Reference
In-Depth Information
8
Contractions and
expansions in gene size
and number
There are now many pathological examples of the deletion, insertion, duplication
and expansion of human genes causing inherited disease. Similar mutations have
however also occurred over evolutionary time. Far from being invariably disad-
vantageous, such mutational changes have often been recruited by the oppor-
tunistic evolutionary process and now contribute to both gene and genome
architecture. These types of mutation have led to significant changes in gene size
and number in different lineages and their contribution to the evolution of extant
human genes will now be reviewed.
8.1 Gross gene deletions in evolution
8.1.1 Gross gene deletions during primate evolution
Gross gene deletions may arise through a number of different recombinational
mechanisms but probably the most common is likely to be
homologous unequal
recombination
(occurring either between related gene sequences or between repeti-
tive elements). Thus,
Alu
sequences flanking deletion breakpoints have been
noted in a considerable number of human genetic conditions and may represent
favored sites for recombination and hotspots for gene deletions (Cooper and
Krawczak, 1993; Chapter 1, section 1.5.4). Chromosomally duplicated regions
(
duplicons
) are often common sites for pathological rearrangements, particularly
gross deletions, since they have the potential to mediate homologous unequal
recombination events (e.g. 15q11-q13; Christian
et al.
, 1999).
Not surprisingly, several instances of gross gene deletion have been noted dur-
ing primate evolution. One such example is the loss of the
1-globin gene in New
World monkeys (with the notable exception of the capuchin monkey,
Cebus alb-
ifrons
) due to a 1.8 kb deletion which has removed most of exon 2, all of intron 2,
exon 3, and much of the 3
2-
globin is the primary fetally expressed globin gene in New World monkeys
whereas in Old World monkeys, it is
flanking region (Meireles
et al
., 1995). As a result,
1-globin.
Another example of gross gene deletion in primates is the loss of one of the hap-
toglobin (
HPP
; 16q22.2) genes in humans which occurred, probably via homolo-
gous unequal recombination, after the separation of the human and chimpanzee
