Long homopurine*homopyrimidine sequences are characteristic of genes expressed in brain and the pseudoautosomal region.
Homo(purine*pyrimidine) sequences (R*Y tracts) with mirror repeat symmetries form stable triplexes that block replication and transcription and promote genetic rearrangements. A systematic search was conducted to map the location of the longest R*Y tracts in the human genome in order to assess their potential function(s). The 814 R*Y tracts with > or =250 uninterrupted base pairs were preferentially clustered in the pseudoautosomal region of the sex chromosomes and located in the introns of 228 annotated genes whose protein products were associated with functions at the cell membrane. These genes were highly expressed in the brain and particularly in genes associated with susceptibility to mental disorders, such as schizophrenia. The set of 1957 genes harboring the 2886 R*Y tracts with > or =100 uninterrupted base pairs was additionally enriched in proteins associated with phosphorylation, signal transduction, development and morphogenesis. Comparisons of the > or =250 bp R*Y tracts in the mouse and chimpanzee genomes indicated that these sequences have mutated faster than the surrounding regions and are longer in humans than in chimpanzees. These results support a role for long R*Y tracts in promoting recombination and genome diversity during evolution through destabilization of chromosomal DNA, thereby inducing repair and mutation.
Bacolla
Albino
A
Institute of Biosciences and Technology, Center for Genome Research, Texas A&M University System Health Science Center, Texas Medical Center, 2121 West Holcombe Blvd, Houston, TX 77030, USA.
Collins
Jack R
JR
Gold
Bert
B
Chuzhanova
Nadia
N
Yi
Ming
M
Stephens
Robert M
RM
Stefanov
Stefan
S
Olsh
Adam
A
Jakupciak
John P
JP
Dean
Michael
M
Lempicki
Richard A
RA
Cooper
David N
DN
Wells
Robert D
RD
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004247:DNA / Q000737:chemistry*; D019143:Evolution, Molecular; D015870:Gene Expression; D015894:Genome, Human; D006801:Humans; D002679:Pan troglodytes / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011687:Purines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D012091:Repetitive Sequences, Nucleic Acid; D012730:Sex Chromosomes; D014018:Tissue Distribution
D011506:Proteins; D011687:Purines; D011743:Pyrimidines; C051802:triplex DNA; D004247:DNA