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BMC Biol 2015 Aug 01;13:56. doi: 10.1186/s12915-015-0165-x.
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Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution.

Marlétaz F , Maeso I , Faas L , Isaacs HV , Holland PW .

BACKGROUND: The functional consequences of whole genome duplications in vertebrate evolution are not fully understood. It remains unclear, for instance, why paralogues were retained in some gene families but extensively lost in others. Cdx homeobox genes encode conserved transcription factors controlling posterior development across diverse bilaterians. These genes are part of the ParaHox gene cluster. Multiple Cdx copies were retained after genome duplication, raising questions about how functional divergence, overlap, and redundancy respectively contributed to their retention and evolutionary fate. RESULTS: We examined the degree of regulatory and functional overlap between the three vertebrate Cdx genes using single and triple morpholino knock-down in Xenopus tropicalis followed by RNA-seq. We found that one paralogue, Cdx4, has a much stronger effect on gene expression than the others, including a strong regulatory effect on FGF and Wnt genes. Functional annotation revealed distinct and overlapping roles and subtly different temporal windows of action for each gene. The data also reveal a colinear-like effect of Cdx genes on Hox genes, with repression of Hox paralogy groups 1 and 2, and activation increasing from Hox group 5 to 11. We also highlight cases in which duplicated genes regulate distinct paralogous targets revealing pathway elaboration after whole genome duplication. CONCLUSIONS: Despite shared core pathways, Cdx paralogues have acquired distinct regulatory roles during development. This implies that the degree of functional overlap between paralogues is relatively low and that gene expression pattern alone should be used with caution when investigating the functional evolution of duplicated genes. We therefore suggest that developmental programmes were extensively rewired after whole genome duplication in the early evolution of vertebrates.

PubMed ID: 26231746
PMC ID: PMC4522105
Article link: BMC Biol
Grant support: [+]

Species referenced: Xenopus tropicalis
Genes referenced: cdx1 cdx2 cdx4
Morpholinos: cdx1 MO2 cdx2 MO1 cdx4 MO1

GEO Series: GSE71006: Xenbase,  NCBI

Article Images: [+] show captions
References [+] :
Anders, HTSeq--a Python framework to work with high-throughput sequencing data. 2015, Pubmed