Evolution of Prdm genes in animals: insights from ...Prdm12 involvement during neurogenesis...

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Prdm12 involvement during neurogenesis Definition of 14 Prdm subfamilies We have searched for Prdm genes in the fully-sequenced genomes of 93 representative metazoan. We identified a total number of 975 Prdm genes in these species. Our phylogenetic analyses of these sequences allowed us to define 14 different subfamilies of Prdm genes. Among the 975 analyzed genes, 930 were confidently assigned to the 14 defined subgroups. The 45 remaining genes were categorized as ‘orphans’. Unrooted PhyML tree of Prdm genes Reconstitution of the ancestral set of Prdm genes in Metazoans Comparison of Prdm gene sets among lineages allow to infer on the ancestral complement of Prdm genes. 11 of the the 14 subfamilies seem ancestral to bilaterians. As uncertainties linger on the deep phylogenetic relationship among metazoans, 4 scenarii are proposed as to the ancestral complement of Prdm genes in Metazoans (green) and putative gene losses (red). The Prdm genes of Platynereis 11 Prdm genes were found in Platynereis’ genome, 10 of which were cloned and their expression patterns analyzed by whole mount in situ hybridizations. Of the 11 bilaterian ancestral complement of Prdm genes, 9 subfamilies are represented in Platynereis (loss of Prdm2 and Prdm6) and 2 subfamilies show lineage specific duplications (Prdm1 & Prdm7/9). Pierre Kerner, David Meulemeester, France Thouzé and Michel Vervoort Evolution and Development of Metazoans Team, Institut Jacques Monod, Université Paris Diderot - CNRS, Paris, France Conclusions Our data provide new insights in the evolution of this important family of transcription factors. The opportunity to investigate the roles of these genes from the phylogenetic vantage point of Platynereis may offer a less biased comparison than with the usual yet usually derived model systems. This is in particular the aim of the investigation of Prdm12 roles in Platynereis for which whole-body gene expression pattern registration, double in situ hybridization and trans-species transgenesis will be performed. Evolution of Prdm genes in animals: insights from comparative genomics and gene expression studies Introduction Prdm genes encode transcription factors with a PRDI-BF1 and RIZ homology (PR) domain and a variable number of zinc finger motifs. These genes show a wide variety of functions, such as important roles in somatic pluripotent stem cells, primordial germ cells or roles in the proper development of neural cells. Whereas the functions of Prdm genes have been carefully studied in some vertebrates, little is known about the evolution of this gene family among metazoans. Hence, we performed a genome-wide identification of Prdm genes in a large set of metazoan species that were used in phylogenetic analyses to define subfamilies of Prdm genes and the most likely ancestral set of Prdm genes present in the last common ancestor of all metazoans, and in the main metazoan groups. To get insight into the evolution of the functions of these genes in bilaterian animals, we cloned and analyzed the expression patterns of the full set of Prdm genes from the emerging annelid model species, Platynereis dumerilii. Adoutte et al., 1999 Demilly et al., 2013 Philippe et al., 2009 Dunn et al., 2008 Pick et al., 2010 Schierwater et al., 2009 PRDM1A PRDM3/16 PRDM4 Ubiquitous expression PRDM7/9 Ubiquitous expression PRDM8 PRDM10/15 Ubiquitous expression PRDM12 PRDM13 PRDM14 24 hpf 48 hpf 55 hpf 72 hpf Midpoint rooted PhyML tree of Prdm genes found in Platynereis (in red), Human, Chicken, Zebrafish, Drosophila and Nematode Recent data suggest that several members of the Prdm family play roles in vertebrate neuronal specification by participating, with bHLH and Homeodomain genes (such as Dbx), in the delineation of progenitor domains during spinal cord development. We are investigating if this role is conserved in Platynereis for Prdm12 as it shows a similar restricted expression pattern during development as to the situation observed in vertebrates. Kinameri et al., 2008 DRG Mouse Dbx Platynereis Prdm12 55 hpf 55 hpf Whole Mount in situ hybridizations of larval stages from 24 hours post fertilization (hpf) to 72hpf. All pictures are ventral views. White dotted delineation of the prototroch. A solid line shows the blastopore in 24hpf larvae.

Transcript of Evolution of Prdm genes in animals: insights from ...Prdm12 involvement during neurogenesis...

Page 1: Evolution of Prdm genes in animals: insights from ...Prdm12 involvement during neurogenesis Definition of 14 Prdm subfamilies We have searched for Prdm genes in the fully-sequenced

Prdm12 involvement during neurogenesis

Definition of 14 Prdm subfamilies We have searched for Prdm genes in the fully-sequenced genomes of 93 representative metazoan. We identified a total number of 975 Prdm genes in these species. Our phylogenetic analyses of these sequences allowed us to define 14 different subfamilies of Prdm genes. Among the 975 analyzed genes, 930 were confidently assigned to the 14 defined subgroups. The 45 remaining genes were categorized as ‘orphans’.

Unrooted PhyML tree of Prdm genes

Reconstitution of the ancestral set of Prdm genes in Metazoans Comparison of Prdm gene sets among lineages allow to infer on the ancestral complement of Prdm genes. 11 of the the 14 subfamilies seem ancestral to bilaterians.

As uncertainties linger on the deep phylogenetic relationship among metazoans, 4 scenarii are proposed as to the ancestral complement of Prdm genes in Metazoans (green) and putative gene losses (red).

The Prdm genes of Platynereis 11 Prdm genes were found in Platynereis’ genome, 10 of which were cloned and their expression patterns analyzed by whole mount in situ hybridizations. Of the 11 bilaterian ancestral complement of Prdm genes, 9 subfamilies are represented in Platynereis (loss of Prdm2 and Prdm6) and 2 subfamilies show lineage specific duplications (Prdm1 & Prdm7/9).

Pierre Kerner, David Meulemeester, France Thouzé and Michel Vervoort Evolution and Development of Metazoans Team, Institut Jacques Monod, Université Paris Diderot - CNRS, Paris, France

Conclusions Our data provide new insights in the evolution of this important family of transcription factors. The opportunity to investigate the roles of these genes from the phylogenetic vantage point of Platynereis may offer a less biased comparison than with the usual yet usually derived model systems. This is in particular the aim of the investigation of Prdm12 roles in Platynereis for which whole-body gene expression pattern registration, double in situ hybridization and trans-species transgenesis will be performed.

Evolution of Prdm genes in animals: insights from comparative genomics and gene expression studies

Introduction Prdm genes encode transcription factors with a PRDI-BF1 and RIZ homology (PR) domain and a variable number of zinc finger motifs. These genes show a wide variety of functions, such as important roles in somatic pluripotent stem cells, primordial germ cells or roles in the proper development of neural cells. Whereas the functions of Prdm genes have been carefully studied in some vertebrates, little is known about the evolution of this gene family among metazoans. Hence, we performed a genome-wide identification of Prdm genes in a large set of metazoan species that were used in phylogenetic analyses to define subfamilies of Prdm genes and the most likely ancestral set of Prdm genes present in the last common ancestor of all metazoans, and in the main metazoan groups. To get insight into the evolution of the functions of these genes in bilaterian animals, we cloned and analyzed the expression patterns of the full set of Prdm genes from the emerging annelid model species, Platynereis dumerilii.

Adou

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Dem

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Philippe et al., 2009 Dunn et al., 2008

Pick et al., 2010 Schierwater et al., 2009

PRDM

1A

PRDM

3/16

PRDM4 Ubiquitous expression

PRDM7/9 Ubiquitous expression

PRDM

8

PRDM10/15 Ubiquitous expression

PRDM

12

PRDM

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PRDM

14

24 hpf 48 hpf 55 hpf 72 hpf

Midpoint rooted PhyML tree of Prdm genes found in Platynereis (in red), Human, Chicken, Zebrafish,

Drosophila and Nematode

Recent data suggest that several members of the Prdm family play roles in vertebrate neuronal specification by participating, with bHLH and Homeodomain genes (such as Dbx), in the delineation of progenitor domains during spinal cord development. We are investigating if this role is conserved in Platynereis for Prdm12 as it shows a similar restricted expression pattern during development as to the situation observed in vertebrates.

Kinameri et al., 2008

DRG

Mouse

Dbx

Platynereis

Prdm12

55 hpf 55 hpf

Whole Mount in situ hybridizations of larval stages from 24 hours post fertilization (hpf) to 72hpf. All pictures are ventral views. White dotted

delineation of the prototroch. A solid line shows the blastopore in 24hpf larvae.