Minor change, major difference: divergent functions of highly conserved cis-regulatory elements subsequent to whole genome duplication events

被引：26

作者：

Goode, Debbie K. ^{[3
]}

Callaway, Heather A. ^{[4
]}

Cerda, Gustavo A. ^{[3
]}

Lewis, Katharine E. ^{[2
,3
]}

Elgar, Greg ^{[1
]}

机构：

[1] MRC Natl Inst Med Res, London NW7 1AA, England

[2] Syracuse Univ, Dept Biol, Syracuse, NY 13244 USA

[3] Dept Physiol Dev & Neurosci, Cambridge CB2 3DY, England

[4] Univ London, London E1 4NS, England

来源：

DEVELOPMENT | 2011年 / 138卷 / 05期

基金：

英国惠康基金;

关键词：

Cis-regulatory elements; DDC model; Enhancer analyses; Evolution; Transcriptional regulation; Whole genome duplication events; IN-VIVO; GENE; EXPRESSION; SEQUENCES; PAX2; ALIGNMENT; LIMB; HOX;

D O I：

10.1242/dev.055996

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Within the vertebrate lineage, a high proportion of duplicate genes have been retained after whole genome duplication (WGD) events. It has been proposed that many of these duplicate genes became indispensable because the ancestral gene function was divided between them. In addition, novel functions may have evolved, owing to changes in cis-regulatory elements. Functional analysis of the PAX2/5/8 gene subfamily appears to support at least the first part of this hypothesis. The collective role of these genes has been widely retained, but sub-functions have been differentially partitioned between the genes in different vertebrates. Conserved non-coding elements (CNEs) represent an interesting and readily identifiable class of putative cis-regulatory elements that have been conserved from fish to mammals, an evolutionary distance of 450 million years. Within the PAX2/5/8 gene subfamily, PAX2 is associated with the highest number of CNEs. An additional WGD experienced in the teleost lineage led to two copies of pax2, each of which retained a large proportion of these CNEs. Using a reporter gene assay in zebrafish embryos, we have exploited this rich collection of regulatory elements in order to determine whether duplicate CNEs have evolved different functions. Remarkably, we find that even highly conserved sequences exhibit more functional differences than similarities. We also discover that short flanking sequences can have a profound impact on CNE function. Therefore, if CNEs are to be used as candidate enhancers for transgenic studies or for multi-species comparative analyses, it is paramount that the CNEs are accurately delineated.

引用

页码：879 / 884

页数：6

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