Limits...
Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution.

Marlétaz F, Maeso I, Faas L, Isaacs HV, Holland PW - BMC Biol. (2015)

Bottom Line: 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.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 therefore suggest that developmental programmes were extensively rewired after whole genome duplication in the early evolution of vertebrates.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK. ferdinand.marletaz@gmail.com.

ABSTRACT

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.

No MeSH data available.


Temporal profile of Cdx expression and regulation. a Normalized expression of the three Cdx paralogues across the developmental time-course. b Transcriptome dynamic across development summarized in seven clusters recapitulating distinct temporal expression profiles using Euclidean distance K-mean clustering. Distribution of Cdx target genes across the seven temporal clusters for the up- (c) and down- (d) regulated genes
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4522105&req=5

Fig6: Temporal profile of Cdx expression and regulation. a Normalized expression of the three Cdx paralogues across the developmental time-course. b Transcriptome dynamic across development summarized in seven clusters recapitulating distinct temporal expression profiles using Euclidean distance K-mean clustering. Distribution of Cdx target genes across the seven temporal clusters for the up- (c) and down- (d) regulated genes

Mentions: Recent reports have argued that gene expression is temporally structured in multiple waves in which key transcription factors play a major activating role [39]. We attempted to determine whether some of the differences in the gene sets regulated by Cdx paralogues were attributable to distinct temporal windows of activity during the developmental time course. All three Cdx genes reach their expression peak at stage 14, the stage investigated in this study (Figs. 2c and 6a); this is followed by a progressive decrease in expression, comparable in Cdx2 and Cdx4 but steeper for Cdx1. We categorized Cdx-regulated genes into seven clusters according to their temporal expression profiles, which distinguishes maternally expressed genes (notably cluster 3) from those initially activated at the mid-blastula transition (MBT) at stage 8 (clusters 2, 5 and 6; Fig. 6b). The proportion of genes regulated by each Cdx gene in each of the temporal clusters is broadly comparable (Fig. 6c, d). We note that all three Cdx genes play a role in repressing the expression of primarily maternal genes after the MBT (cluster 3, up-regulated by MO treatment; Fig. 6c). All three genes, but especially Cdx4, also play roles in activation of zygotic genes whose expression starts at the MBT (cluster 5, down-regulated by MO treatment; Fig. 6d). In addition, Cdx2 plays a distinct role in activating genes with later expression onset (cluster 2, MO down-regulation; Fig. 6d), and repressing some post-MBT zygotic genes (cluster 5, MO up-regulation; Fig. 6c). In summary, examination of temporal expression profiles of Cdx gene targets did not suggest that the stronger Cdx4 effect is related to a distinct activation timing of Cdx genes. Instead, this profiling reveals a shared role in modulating gene expression immediately after the MBT, coupled with subtle differences in the maintenance of a dynamic transcriptome at later developmental stages.Fig. 6


Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution.

Marlétaz F, Maeso I, Faas L, Isaacs HV, Holland PW - BMC Biol. (2015)

Temporal profile of Cdx expression and regulation. a Normalized expression of the three Cdx paralogues across the developmental time-course. b Transcriptome dynamic across development summarized in seven clusters recapitulating distinct temporal expression profiles using Euclidean distance K-mean clustering. Distribution of Cdx target genes across the seven temporal clusters for the up- (c) and down- (d) regulated genes
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522105&req=5

Fig6: Temporal profile of Cdx expression and regulation. a Normalized expression of the three Cdx paralogues across the developmental time-course. b Transcriptome dynamic across development summarized in seven clusters recapitulating distinct temporal expression profiles using Euclidean distance K-mean clustering. Distribution of Cdx target genes across the seven temporal clusters for the up- (c) and down- (d) regulated genes
Mentions: Recent reports have argued that gene expression is temporally structured in multiple waves in which key transcription factors play a major activating role [39]. We attempted to determine whether some of the differences in the gene sets regulated by Cdx paralogues were attributable to distinct temporal windows of activity during the developmental time course. All three Cdx genes reach their expression peak at stage 14, the stage investigated in this study (Figs. 2c and 6a); this is followed by a progressive decrease in expression, comparable in Cdx2 and Cdx4 but steeper for Cdx1. We categorized Cdx-regulated genes into seven clusters according to their temporal expression profiles, which distinguishes maternally expressed genes (notably cluster 3) from those initially activated at the mid-blastula transition (MBT) at stage 8 (clusters 2, 5 and 6; Fig. 6b). The proportion of genes regulated by each Cdx gene in each of the temporal clusters is broadly comparable (Fig. 6c, d). We note that all three Cdx genes play a role in repressing the expression of primarily maternal genes after the MBT (cluster 3, up-regulated by MO treatment; Fig. 6c). All three genes, but especially Cdx4, also play roles in activation of zygotic genes whose expression starts at the MBT (cluster 5, down-regulated by MO treatment; Fig. 6d). In addition, Cdx2 plays a distinct role in activating genes with later expression onset (cluster 2, MO down-regulation; Fig. 6d), and repressing some post-MBT zygotic genes (cluster 5, MO up-regulation; Fig. 6c). In summary, examination of temporal expression profiles of Cdx gene targets did not suggest that the stronger Cdx4 effect is related to a distinct activation timing of Cdx genes. Instead, this profiling reveals a shared role in modulating gene expression immediately after the MBT, coupled with subtle differences in the maintenance of a dynamic transcriptome at later developmental stages.Fig. 6

Bottom Line: 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.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 therefore suggest that developmental programmes were extensively rewired after whole genome duplication in the early evolution of vertebrates.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK. ferdinand.marletaz@gmail.com.

ABSTRACT

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.

No MeSH data available.