New noncoding RNA genes continue to be discovered by less systematic means, which makes it seem likely that a systematic RNA genefinding algorithm would be of use. Gene discovery methods (whether experimental or computational) typically assume that the target is a protein coding gene that produces a messenger RNA. The number and diversity of ncRNA genes remains poorly understood, despite the availability of many complete genome sequences. For ncRNA genes, there are as yet no general genefinding algorithms. For protein-coding genes, we have computational genefinding tools that predict novel genes in genome sequence data with reasonable efficiency. Some genes produce functional noncoding RNAs (ncRNAs) instead of coding for proteins. Tests suggest that this approach detects noncoding RNA genes with a fair degree of reliability. We have implemented this approach as a program, QRNA, which we consider to be a prototype structural noncoding RNA genefinder. from a BLASTN comparison of two related genomes) we classify the alignment into the coding, RNA, or null class according to the posterior probability of each class. Given an input pairwise sequence alignment (e.g. We formalize this intuition using three probabilistic "pair-grammars": a pair stochastic context free grammar modeling alignments constrained by structural RNA evolution, a pair hidden Markov model modeling alignments constrained by coding sequence evolution, and a pair hidden Markov model modeling a null hypothesis of position-independent evolution. A conserved coding region tends to show a pattern of synonymous substitutions, whereas a conserved structural RNA tends to show a pattern of compensatory mutations consistent with some base-paired secondary structure. The key idea is to test the pattern of substitutions observed in a pairwise alignment of two homologous sequences. We describe a comparative sequence analysis algorithm for detecting novel structural RNA genes. ![]() A reliable general purpose computational genefinder for noncoding RNA genes has been elusive. ![]() Noncoding RNA gene sequences do not have strong statistical signals, unlike protein coding genes. Noncoding RNA genes produce transcripts that exert their function without ever producing proteins.
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