Local conservation scores without a priori assumptions on neutral substitution rates |
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Authors: | Janis Dingel Pavol Hanus Niccolò Leonardi Joachim Hagenauer Jürgen Zech Jakob C Mueller |
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Institution: | 1.Institute for Communications Engineering,Technische Universit?t München,Munich,Germany;2.MRC Clinical Sciences Centre,Imperial College,London,UK;3.Max-Planck Institute for Ornithology,Starnberg-Seewiesen,Germany |
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Abstract: | Background Comparative genomics aims to detect signals of evolutionary conservation as an indicator of functional constraint. Surprisingly,
results of the ENCODE project revealed that about half of the experimentally verified functional elements found in non-coding
DNA were classified as unconstrained by computational predictions. Following this observation, it has been hypothesized that
this may be partly explained by biased estimates on neutral evolutionary rates used by existing sequence conservation metrics.
All methods we are aware of rely on a comparison with the neutral rate and conservation is estimated by measuring the deviation
of a particular genomic region from this rate. Consequently, it is a reasonable assumption that inaccurate neutral rate estimates
may lead to biased conservation and constraint estimates. |
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