Ubiquitous selective constraints in the Drosophila genome revealed by a genome-wide interspecies comparison
- 2 June 2006
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 16 (7), 875-884
- https://doi.org/10.1101/gr.5022906
Abstract
Non-coding DNA comprises ∼80% of the euchromatic portion of the Drosophila melanogaster genome. Non-coding sequences are known to contain functionally important elements controlling gene expression, but the proportion of sites that are selectively constrained is still largely unknown. We have compared the complete D. melanogaster and Drosophila simulans genome sequences to estimate mean selective constraint (the fraction of mutations that are eliminated by selection) in coding and non-coding DNA by standardizing to substitution rates in putatively unconstrained sequences. We show that constraint is positively correlated with intronic and intergenic sequence length and is generally remarkably strong in non-coding DNA, implying that more than half of all point mutations in the Drosophila genome are deleterious. This fraction is also likely to be an underestimate if many substitutions in non-coding DNA are adaptively driven to fixation. We also show that substitutions in long introns and intergenic sequences are clustered, such that there is an excess of substitutions Drosophila genome. Most deleterious mutations therefore occur in non-coding DNA, and these may make an important contribution to a wide variety of evolutionary processes.Keywords
This publication has 52 references indexed in Scilit:
- Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomesGenome Research, 2005
- Intron Size and Exon Evolution in DrosophilaGenetics, 2005
- Insertion/Deletion and Nucleotide Polymorphism Data Reveal Constraints in Drosophila melanogaster Introns and Intergenic RegionsGenetics, 2005
- Evidence for Widespread Degradation of Gene Control Regions in Hominid GenomesPLoS Biology, 2005
- Combined Evidence Annotation of Transposable Elements in Genome SequencesPLoS Computational Biology, 2005
- MCALIGN: Stochastic Alignment of Noncoding DNA Sequences Based on an Evolutionary Model of Sequence EvolutionGenome Research, 2004
- Patterns of Evolutionary Constraints in Intronic and Intergenic DNA of DrosophilaGenome Research, 2004
- Pseudogene evolution and natural selection for a compact genomeJournal of Heredity, 2000
- CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choiceNucleic Acids Research, 1994
- A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequencesJournal of Molecular Evolution, 1980