Contractions and expansions in gene size and number - Human Gene Evolution - page 357

8.7 Coding sequence expansion and contraction resulting
from the introduction or removal of initiation and
termination codons
The mutation of initiation codons leading to the extension of the protein coding
sequence of a gene is known to be a cause, albeit an infrequent one, of human
genetic disease (Cooper and Krawczak, 1993). Such mutations have however also
occurred on a number of occasions during gene evolution. Thus, an ATG GTG
substitution occurred in the Met initiator codon of the ZNF80 (3q13.3) gene in
the common ancestor of African green monkey and rhesus macaque which
resulted in a change in the site of translational initiation to a location 20 codons
amino terminal to the Met initiator codon used by humans, chimpanzees and
gorillas (Di Cristofano et al ., 1995). However, in African green monkey, the
ZNF80 protein is only 213 amino acid residues in length (as compared to 273
residues in humans and the great apes and 293 residues in rhesus macaque) owing
to truncation of the protein due to an additional GAG TAG substitution intro-
ducing a novel termination codon (Di Cristofano et al ., 1995).
Another example of mutation resulting in the species-specific use of alternative
initiation codons is provided by an ATG→ ATA transition in the human hepatic
peroxisomal L -alanine: glyoxylate aminotransferase 1 ( AGXT ; 2q36-q37) gene
(Takada et al ., 1990). This lesion removed the original initiation codon and an
alternative downstream initiation codon is used in the translation of the human
AGXT transcript. The rat Agxt orthologue encodes a protein which, by compari-
son with the human protein, possesses an extra 22 amino terminal amino acids
specifying a leader sequence thought to contain a mitochondrial targeting signal
that is absent in the human protein.
The mutational removal of a termination codon may also lead to the elongation
of a protein product. One example of this is provided by the porcine P-glycopro-
tein genes whose coding regions may be seen to have been extended by such a
mutation when compared to the human orthologous proteins ( PGY1 , PGY3 ;
7q21; Childs and Ling, 1996).
8.8 Minisatellites, microsatellites and telomeric repeats
Repetition is the only form of permanence that nature can achieve.
George Santayana (1922)
A detailed discussion of the evolution of the various families of satellite, min-
isatellite and microsatellite DNA would be somewhat tangential to the remit of
this volume and would merely serve to recapitulate a previous volume in this
series. However, a brief resumé will be given to provide the necessary background
to guide the interested reader to the relevant literature.
8.8.1 Minisatellite DNA sequences
Minisatellite DNA sequences occur in all eukaryotes from yeast to human (Haber