The mystery of extreme non-coding conservation

被引：50
作者：
Harmston, Nathan [1 ,2 ]
Baresic, Anja [1 ,2 ]
Lenhard, Boris [1 ,2 ,3 ]
机构：
[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Inst Clin Sci, London W12 0NN, England
[2] MRC Clin Sci Ctr, London W12 0NN, England
[3] Univ Bergen, Dept Informat, N-5008 Bergen, Norway
来源：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES | 2013年 / 368卷 / 1632期
基金：
英国医学研究理事会;
关键词：
vertebrate cis-regulation; genome evolution; conserved non-coding elements; cis-regulatory; evolution; ULTRACONSERVED ELEMENTS; REGULATORY ELEMENTS; PURIFYING SELECTION; ADAPTIVE EVOLUTION; GENE-REGULATION; HUMAN GENOME; ENHANCER; VERTEBRATE; SEQUENCE; TRANSCRIPTION;
D O I：
10.1098/rstb.2013.0021
中图分类号：
Q [生物科学];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：12
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