Repetitive Elements May Comprise Over Two-Thirds of the Human Genome

By A. P. Jason De Koning, W. Gu, Todd A. Castoe, Mark A. Batzer, D. Pollock, Gregory P. Copenhaver. PLoS Genetics, 2011

1,092 citations recorded by the source corpus.

Transposable elements (TEs) are conventionally identified in eukaryotic genomes by alignment to consensus element sequences. Using this approach, about half of the human genome has been previously identified as TEs and low-complexity repeats. We recently developed a highly sensitive alternative de novo strategy, P-clouds, that instead searches for clusters of high-abundance oligonucleotides that are related in sequence space (oligo “clouds”). We show here that P-clouds predicts >840 Mbp of additional repetitive sequences in the human genome, thus suggesting that 66%–69% of the human genome is repetitive or repeat-derived. To investigate this remarkable difference, we conducted detailed analyses of the ability of both P-clouds and a commonly used conventional approach, RepeatMasker (RM), to detect different sized fragments of the highly abundant human Alu and MIR SINEs. RM can have surprisingly low sensitivity for even moderately long fragments, in contrast to P-clouds, which has good sensitivity down to small fragment sizes (∼25 bp). Although short fragments have a high intrinsic probability of being false positives, we performed a probabilistic annotation that reflects this fact. We further developed “element-specific” P-clouds (ESPs) to identify novel Alu and MIR SINE elements, and using it we identified ∼100 Mb of previously unannotated human elements. ESP estimates of new MIR sequences are in good agreement with RM-based predictions of the amount that RM missed. These results highlight the need for combined, probabilistic genome annotation approaches and suggest that the human genome consists of substantially more repetitive sequence than previously believed.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/b653772a6cec5ac2527b4ebd1f39c31f05b8b429

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Citations in the corpus

KRAB zinc finger proteins (2017, background): “However, because TEs become unrecognizable over time owing to mutational drift, it is likely that this represents an underestimate of their contribution to our genetic make-up (de Koning et al., 2011; Hubley et al., 2016).”
Dfam: a database of repetitive DNA based on profile hidden Markov models (2012, methodology): “Recent results combining a method called P-clouds (13) with RepeatMasker results suggest that at least 66% of”
Long Noncoding RNAs: Past, Present, and Future (2013, background): “The remaining noncoding space was termed “junk DNA” (Comings 1972; Ohno 1972) due to its overwhelming burden of transposons, pseudogenes, and simple repeats [in total accounting for 50–70% of the human genome (de Koning et al. 2011)].”