Raising the estimate of functional human sequences: Figure 1.

Abstract

While less than 1.5% of the mammalian genome encodes proteins, it is now evident that the vast majority is transcribed, mainly into non-protein-coding RNAs. This raises the question of what fraction of the genome is functional, i.e., composed of sequences that yield functional products, are required for the expression (regulation or processing) of these products, or are required for chromosome replication and maintenance. Many of the observed noncoding transcripts are differentially expressed, and, while most have not yet been studied, increasing numbers are being shown to be functional and/or trafficked to specific subcellular locations, as well as exhibit subtle evidence of selection. On the other hand, analyses of conservation patterns indicate that only ∼5% (3%-8%) of the human genome is under purifying selection for functions common to mammals. However, these estimates rely on the assumption that reference sequences (usually ancient transposon-derived sequences) have evolved neutrally, which may not be the case, and if so would lead to an underestimate of the fraction of the genome under evolutionary constraint. These analyses also do not detect functional sequences that are evolving rapidly and/or have acquired lineage-specific functions. Indeed, many regulatory sequences and known functional noncoding RNAs, including many microRNAs, are not conserved over significant evolutionary distances, and recent evidence from the ENCODE project suggests that many functional elements show no detectable level of sequence constraint. Thus, it is likely that much more than 5% of the genome encodes functional information, and although the upper bound is unknown, it may be considerably higher than currently thought.

When Competing Viruses Unify: Evolution, Conservation, and Plasticity of Genetic Identities

“…Indeed, understanding the origin of transposable RNA-based networks (and network security) has always been challenging as networks do not fit into tree-based analogies (Bapteste et al 2013;Daly et al 2011;Feschotte 2008). It also appears that various small non-coding RNAs participate in 'multi-task' networks and such RNAs tend to be transcribed from 'junk' retroposons (Mattick 2011;Mattick and Gagen 2001;Mattick and Makunin 2006;Pheasant and Mattick 2007). In terms of active editors of the human genome, there are about 330,000 solo LTRs Greene 2011, 2012) each of which must have initially corresponded to an intact ERV (*10 kb) subsequently lost by deletion.…”

New meaning in the message: Noncoding RNAs and their role in retinal development

“…Indeed, by all measures and in all tested organisms from C. elegans to humans, the majority of the genomes is transcribed (Kapranov et al, 2007). Though little is known about what, if any, role is played by the great majority of these transcripts, recent years have seen a steady increase in the number of ncRNAs for which a specific cellular function has been identified (Cao et al, 2006;Mattick, 2006, 2007;Pang et al, 2007;Pheasant and Mattick, 2007;Prasanth and Spector, 2007;Taft et al, 2007). Unsurprisingly, the categories of ncRNAs with demonstrated function are highly diverse.…”

Scoring the collective effects of SNPs: association of minor alleles with complex traits in model organisms

“…In contrast, experimental science found little evidence for the neutral assumption. A majority of the noncoding parts of the human genome are transcribed [14], and numerous experimental researchers have now recognized an important functional role for these non-coding RNAs (for a review see [13,15]). Furthermore, we have recently proposed a more complete theory to supersede the neutral hypothesis and a key prediction of our theory is that the majority of a genome are functional [16,17].…”