The mystery of extreme non-coding conservation.
Regions of several dozen to several hundred base pairs of extreme conservation have been found in non-coding regions in all metazoan genomes. The distribution of these elements within and across genomes has suggested that many have roles as transcriptional regulatory elements in multi-cellular organization, differentiation and development. Currently, there is no known mechanism or function that would account for this level of conservation at the observed evolutionary distances. Previous studies have found that, while these regions are under strong purifying selection, and not mutational coldspots, deletion of entire regions in mice does not necessarily lead to identifiable changes in phenotype during development. These opposing findings lead to several questions regarding their functional importance and why they are under strong selection in the first place. In this perspective, we discuss the methods and techniques used in identifying and dissecting these regions, their observed patterns of conservation, and review the current hypotheses on their functional significance.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London and MRC Clinical Sciences Centre, , Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
Nathan
N
Harmston
Anja
A
Baresic
Boris
B
Lenhard
D000818:Animals; D017124:Conserved Sequence / Q000235:genetics*; D021901:DNA, Intergenic / Q000235:genetics*; D019143:Evolution, Molecular; D016678:Genome / Q000235:genetics*; D008957:Models, Genetic; D012641:Selection, Genetic
D021901:DNA, Intergenic
cis-regulatory; conserved non-coding elements; evolution; genome evolution; vertebrate cis-regulation