Physiol Genomics 2001 Apr 2;5(3):113-118
Genetic variation in mRNA coding sequences of highly conserved genes.
Ten Asbroek AL, Olsen J, Housman D, Baas F, Stanton V JR
Neurozintuigen Laboratory, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands,
Variagenics, Cambridge 02139-1562, Center for Cancer Research, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02140.
[Record supplied by publisher]
The frequency and distribution of genetic polymorphism in the human genome is a question of
major importance. We have studied this in highly conserved genes, which encode crucial
functions such as DNA replication, mRNA transcription, and translation. Evolutionary
comparisons suggest that these genes are under particularly strong selective pressure, and their
frequency of nucleotide sequence polymorphism would be expected to represent a minimum
estimate for sequence variation throughout the genome. We have analyzed the complete coding
sequence and the 3'-untranslated region (3'-UTR) of 22 human genes, most of which have
homologs in all cellular organisms and all of which are at least 25% amino acid identical to
homologs in yeast. Comparisons with similar studies of less conserved human disease genes
indicate that 1) evolutionarily conserved genes are, on average, less polymorphic than disease
related genes; 2) the difference in polymorphism levels is attributable almost entirely to reduced
levels of variation in protein coding sequences, whereas noncoding sequences have similar levels
of polymorphism; and 3) the character of polymorphism, in terms of the spectrum and frequency
of mutational changes, is similar. |
