Contractions and expansions in gene size and number - Human Gene Evolution - page 343

Exon Ib Exon IIa Alu 29 Alu 44 Alu 56 Alu 60 Alu 77 Exon TM

282 nt

Exon IIz
Alu 44

Exon Ib Exon IIa Alu 29 Alu 56 Alu 60 Alu 77 Exon TM

93 nt

Exon IIy
Alu 60 Exon Ib Exon IIa Alu 29 Alu 44 Alu 56 Alu 77 Exon TM

93 nt

Figure 8.8. A scheme for alternative splicing in the human biliary glycoprotein ( BGP )
mRNA. Boxes represent exons and arrows the five intronic antisense Alu elements.
TM, exon encoding the transmembrane domain. Dotted lines indicate the splicing
patterns found in the three cDNAs (after Barnet et al ., 1993).

mediated insertion of Alu repeats has been an important evolutionary mechanism
for creating diversity at the protein level.

Alu sequence incorporation by intron sliding. An alternative mechanism of
Alu sequence incorporation into gene coding regions is intron sliding, and is illus-
trated by the example of the human HLA-DRB1 (6p21.3) gene; an intronic Alu
sequence has been incorporated into exon 4 of the HLA-DR- 1 mRNA (Labuda

et al., 1995; Figure 8.9). Among three variants of the HLA-DR- 1 cDNA,

detected by library screening, one was considered to be the usual form, whereas
two others were alternatively spliced owing to a lack of splicing at the intron 5
donor site. As a result, exon 5 was extended into a nearby downstream Alu
sequence in intron 5, either to include a stop codon within the Alu sequence, or to
be spliced with exon 6 (the open reading frame in the extended exon 5 matches
that of exon 6). These three cDNA clones may thus illustrate two phases of intron
sliding: the inactivation of an existing splice site followed by the activation of a
cryptic one.