The mystery of extreme non-coding conservation
Nathan Harmston1,†, Anja Barešić1,† and Boris Lenhard1,2⇑
- Author Affiliations
1Institute of Clinical Sciences, Faculty of Medicine, Imperial College London and MRC Clinical Sciences Centre, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
2Department of Informatics, University of Bergen, Thormøhlensgate 55, 5008 Bergen, Norway
e-mail: b.lenhard@imperial.ac.uk
↵† These two authors contributed equally to this article.
Abstract
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.
vertebrate cis-regulation genome evolution conserved non-coding elements cis-regulatory evolution
+++++
EXCERPT/EXCERTO
Examples of teleological language/Exemplos de linguagem teleológica:
"Lowe et al. proposed that, within vertebrates, there have been three distinct periods of CNE [conserved non-coding element] recruitment around specific groups of genes. They suggest that this pattern is the result of regulatory innovations, which led to important phenotypic changes during vertebrate evolution. Prior to the divergence of mammals from reptiles and birds, it appears that CNEs were preferentially recruited near TFs and their developmental targets. This was followed by a gradual decline in recruitment near these genes, accompanied by [a recruitment] increase near proteins involved in extracellular signalling, and then [a recruitment] increase in placental mammals near genes responsible for post-translational modification and intracellular signalling. An analysis of CNE gain in the primate and rodent lineage has found that CNEs are either recruited near genes which have not previously been associated with CNEs, or are added near genes which are already flanked by CNEs. The interpretation was that the first set of genes is enriched in functions pertaining to nervous system development, whereas the latter contains genes involved in transcriptional regulation and anatomical development."
"Lowe et al. proposed that, within vertebrates, there have been three distinct periods of CNE [conserved non-coding element] recruitment around specific groups of genes. They suggest that this pattern is the result of regulatory innovations, which led to important phenotypic changes during vertebrate evolution. Prior to the divergence of mammals from reptiles and birds, it appears that CNEs were preferentially recruited near TFs and their developmental targets. This was followed by a gradual decline in recruitment near these genes, accompanied by [a recruitment] increase near proteins involved in extracellular signalling, and then [a recruitment] increase in placental mammals near genes responsible for post-translational modification and intracellular signalling. An analysis of CNE gain in the primate and rodent lineage has found that CNEs are either recruited near genes which have not previously been associated with CNEs, or are added near genes which are already flanked by CNEs. The interpretation was that the first set of genes is enriched in functions pertaining to nervous system development, whereas the latter contains genes involved in transcriptional regulation and anatomical development."
