Biology Reference
In-Depth Information
section 1.2.1). These genes belong to one of two distinct classes. The first is exem-
plified by the ubiquitin C (
UBC
; 12q24) gene which contains 9 direct repeats of
the ubiquitin amino acid sequence with no spacer regions and no introns (Wiborg
et al
., 1985). The
UBC
locus has a single termination codon and yields a 2500
nucleotide mRNA which upon translation generates a polyubiquitin precursor
molecule which is post-translationally cleaved to active ubiquitin. Unequal cross-
ing over events at the
UBC
locus have been responsible for polymorphism in ubiq-
uitin repeat unit number (Baker and Board, 1989). A second human polyubiquitin
gene (
UBB
, 17p11-p12) with 3 repeat units yields a 1000 nucleotide mRNA (Webb
et al
., 1990). The second class comprises ubiquitin fusion genes which encode a sin-
gle ubiquitin fused in-frame to a ribosomal protein of either 52 (
UBA52
; 19p13;
Baker and Board, 1991; 1992) or 76-80 (
UBA80
) amino acids (Lund
et al
., 1985).
The number of nucleotide differences between ubiquitin repeats within a given
species is very low as compared to those between species (Sharp and Li, 1987).
Thus, repeats within a locus share a more recent common ancestor than any two
repeats in different species. This finding is explicable in terms of concerted evo-
lution, probably mediated by unequal crossing over or gene conversion (Sharp
and Li, 1987; Vrana and Wheeler, 1996). In human, concerted evolution is evi-
dent both within and between ubiquitin loci but appears to occur at a higher rate
for some repeats than others (Tan
et al
., 1993).
An overview of the evolution of multigene families in eukaryotes.
During
eukaryotic evolution, gene families have been created by sequential, phased
rounds of gene duplication with specific genes becoming duplicated as a result of
whole genome duplications, subchromosomal regional duplications, and through
the rather more discrete duplication of individual gene loci. Since the number of
genes in a gene family varies quite widely, we may surmise that some sequences
are more predisposed to duplicate than others. As a consequence of their common
origin, multigene family members usually have a similar structure both in terms
of their nucleotide sequences and exon-intron organization (although the gain or
loss of some introns in some members can serve to obscure their common ances-
try). Whereas some genes have retained their syntenic relationship with each
other after duplication and have remained chromosomally linked for relatively
long periods of evolutionary time, others have been translocated to another chro-
mosomal location. In some gene families, new rounds of gene duplication have
then led to the formation of gene clusters. Once diversification of gene clusters,
sub-clusters and individual genes had occurred through the acquisition of com-
paratively subtle mutational changes, the duplication of entire gene clusters as
well as portions of clusters would then have led to the emergence of a sub-family
structure within the gene family.
Diversification of individual genes within multigene families has occurred in a
host of different ways in different lineages. Amino acid substitutions may appear
to constitute relatively subtle structural changes but these changes can be quite
dramatic in functional terms if, for example, substrate specificity is altered.
Diversification can also proceed by internal duplication and deletion (e.g. gain or
loss of individual exons), the insertion or removal of individual amino acid
residues, repeat expansion and by the more complex processes of gene conversion,
