Monday, September 30, 2013

Fwd: Small Insertions Are More Deleterious than Small Deletions in Human Genomes

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Small Insertions Are More Deleterious than Small Deletions in Human Genomes: "

ABSTRACT

Although lines of evidence suggest that small insertions and deletions differ in their mechanisms of formation, there remains the debate on whether natural selection acts differently on the two indel types. Currently available personal genomes and the 1000 Genomes Project permit population level and genome scale comparison of the selection regimes on the two indel types. We first developed a statistical model to evaluate the indel frequency biases of the 1000 Genomes Project phase 1 data. We then identified four independent lines of evidence demonstrating that human small (1–4 bp) insertions are on average more deleterious than deletions. This genome-wide selection pattern is not affected by methodology, demography, and regional differences including indel density, introns versus exons, repeats versus nonrepeats, recombination rates, and the timing of DNA replication. This selection pattern has a profound effect on indel frequency spectra, deletional bias, and local single-nucleotide mutation rates. Finally, we observed that small insertions appear to be more actively implicated in shaping fast-evolving genomic sequences (or nonconserved regions).

Thumbnail image of graphical abstract

There has been long debate on whether insertions or deletions are more deleterious. We here identified four lines of evidence from personal genomes and data from the 1000 Genomes Project to demonstrate that human small insertions are on average under stronger negative selection than small deletions. Moreover, we observed that small insertions are more actively implicated in fast sequence evolution.

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(Via human mutation.)