Comparative analysis of genome tiling array data reveals many novel primate-specific functional RNAs in human.
BACKGROUND
Widespread transcription activities in the human genome were recently observed in high-resolution tiling array experiments, which revealed many novel transcripts that are outside of the boundaries of known protein or RNA genes. Termed as "TARs" (Transcriptionally Active Regions), these novel transcribed regions represent "dark matter" in the genome, and their origin and functionality need to be explained. Many of these transcripts are thought to code for novel proteins or non-protein-coding RNAs. We have applied an integrated bioinformatics approach to investigate the properties of these TARs, including cross-species conservation, and the ability to form stable secondary structures. The goal of this study is to identify a list of potential candidate sequences that are likely to code for functional non-protein-coding RNAs. We are particularly interested in the discovery of those functional RNA candidates that are primate-specific, i.e. those that do not have homologs in the mouse or dog genomes but in rhesus.


RESULTS
Using sequence conservation and the probability of forming stable secondary structures, we have identified approximately 300 possible candidates for primate-specific noncoding RNAs. We are currently in the process of sequencing the orthologous regions of these candidate sequences in several other primate species. We will then be able to apply a "phylogenetic shadowing" approach to analyze the functionality of these ncRNA candidates.


CONCLUSIONS
The existence of potential primate-specific functional transcripts has demonstrated the limitation of previous genome comparison studies, which put too much emphasis on conservation between human and rodents. It also argues for the necessity of sequencing additional primate species to gain a better and more comprehensive understanding of the human genome.
Zhang
Zhaolei
Z
Banting & Best Department of Medical Research, Donnelly CCBR, University of Toronto, Toronto, ON M5S 3E1, Canada. Zhaolei.Zhang@utoronto.ca
Pang
Andy Wing Chun
AW
Gerstein
Mark
M
D000818:Animals; D001483:Base Sequence; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D002679:Pan troglodytes / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000502:physiology*; D022661:RNA, Untranslated; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014158:Transcription, Genetic
D012333:RNA, Messenger; D022661:RNA, Untranslated