Biology Reference
In-Depth Information
of recombination between nonhomologous regions of chromosomes,
causing deletions, duplications, inversions, and translocations. TEs are
therefore an important generator of genomic variation upon which
natural selection may act.
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6. RNA Genes and Conserved Noncoding
Sequences
One of the surprises of the genomics era that came with the sequencing
of the human genome, followed by the mouse and rat genomes, is that
only about 2% of the mammalian genomic DNA encodes proteins. The
remaining regions, including TEs, without any apparent value to the
host genomes were initially designated as junk DNA. Today, however,
closer comparative analyses of orthologous genomic regions in multiple
species have highlighted a substantial number of conserved non-
protein-coding sequences, illustrating the power (and limitations) of com-
putational comparative genomics. The recent discovery and appreciation
of the biological importance of microRNA genes (miRNAs) has high-
lighted the need to identify and characterize non-protein-coding RNA
genes (ncRNAs) beyond the well-known transfer and ribosomal RNAs,
as well as the generally termed conserved noncoding sequences (CNSs)
including the ultraconserved elements.
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The pilot ENCODE project
1
now estimates that at least about 4%-7% of the human genome is under
purifying selection, representing a much larger functional fraction and
suggesting that the repertoire of poorly characterized functionally
important elements is at least as large as the repertoire of protein-
coding genes.
Knowledge of ncRNAs before whole-genome sequencing projects
was limited to a handful of RNA genes including tRNAs, which transfer
specific amino acids onto polypeptide chains during translation, and
rRNAs, which constitute the structural basis and the peptidyl transferase
activity of ribosomes. The prediction of genes encoding these well-
known RNA genes, however, remains nontrivial. rRNA genes are found
in multiple-copy clusters, where they experience concerted evolution
keeping them highly uniform in sequence, which frequently presents a
problem when assembling these genomic regions. As rRNA genes are
