Biology Reference
In-Depth Information
often flanked by short 8-12 bp direct terminal repeats, they may have arisen by
RNA-mediated transposition (McBride
et al
., 1989).
A human gene (
TRSP
) encoding an opal suppressor phosphoserine tRNA has
been characterized on chromosome 19q13 (O'Neill
et al
., 1985). This tRNA is
potentially capable of suppressing nonsense mutations since it is able to recognize
a different codon than that corresponding to the amino acid it carries. This abil-
ity is conferred upon it by dint of a base change in its anticodon which allows it to
translate a UGA Stop codon and insert a serine at this position.
Phylogenetic studies of tRNA genes have shown that members of isoaccepting
groups do not invariably cluster together (Saks and Sampson, 1995). It would
appear that during evolution, tRNAs have been recruited from one isoaccepting
group to another by mutations in the anticodon (Saks and Sampson, 1995).
The aminoacyl-tRNA synthetases constitute a large gene family in the human
genome including glutaminyl/prolyl (
EPRS
; 1q32-q42), lysyl (
KARS
; 16q23-
q24), alanyl (
AARS
; 16q22), arginyl (
RARS
; 5pter-q11), valyl (
VARS1
; 9), his-
tidyl (
HARS
; chromosome 5), asparginyl (
NARS
; chromosome 18), threonyl
(
TARS
; 5p13-cen), methionyl (
MARS
; chromosome 12), isoleucyl (
IARS
; 9q21),
glycyl (
GARS
; 7p15), tryptophanyl (
WARS
; 14q32), cysteinyl (
CARS
; 11p15.5)
and leucyl (
LARS
; 5cen-q11). Whilst many of the members of this gene family are
chromosomally widely dispersed, similar chromosomal locations for some mem-
bers are suggestive of linkage. The aminoacyl-tRNA synthetases may be grouped
into two distinct classes, each with ten members, based upon sequence data and
structure (Cusack
et al
., 1991; Eriani
et al
., 1990). These groups are thought to
have arisen from two progenitor aminoacyl-tRNA synthetases by gene duplica-
tion and divergence (Nagel and Doolittle, 1995). Despite their ancient origin and
their presence in both prokaryotes and eukaryotes, sequence similarity between
aminoacyl-tRNA synthetases from eukaryotes and prokaryotes may be as low as
15% (Nagel and Doolittle, 1995).
Interestingly, there is a relationship between synthetase class and the
nucleotide that is conserved at position 73. Eight of the ten tRNAs that are
aminoacylated by class I synthetases have an alanine residue at this position
whereas those that are aminoacylated by class II synthetases manifest greater
nucleotide diversity (Saks and Sampson, 1995). It is clear that the genes for both
tRNAs and aminoacyl-tRNA synthetases have a very long evolutionary history.
Their origins and the means by which they may have coevolved are as yet unclear
(Saks and Sampson, 1995) although recent work has suggested that the tRNA syn-
thetases may have been preceded by their tRNAs (Ribas de Pouplana
et al
., 1998).
Ubiquitin genes.
The ubiquitin genes are extremely highly conserved 76 amino
acid proteins which are required for ATP-dependent nonlysosomal intracellular
protein degradation of defective proteins and proteins with a rapid turnover
(Schlesinger and Bond 1987). Although found in all eukaryotes, they have not so
far been found in prokaryotes.
The human genome contains multiple ubiquitin-related sequences most of
which are processed pseudogenes (Schlesinger and Bond, 1987). There are how-
ever at least four functional ubiquitin genes which together have provided an
interesting challenge to carefully crafted general definitions of the gene (Chapter 1,
