The core transcriptome of mammalian placentas and the divergence of expression with placental shape

Abstract

Introduction: The placenta is arguably the most anatomically variable organ in mammals even though its primary function is conserved.

Method: Using RNA-Seq, we measured the expression profiles of 55 term placentas of 14 species of mammals representing all major eutherian superordinal clades and marsupials, and compared the evolution of expression across clades.

Results: We identified a set of 115 core genes which is expressed (FPKM ≥10) in all eutherian placentas, including genes with immune-modulating properties (ANXA2, ANXA1, S100A11, S100A10, and LGALS1), cell-cell interactions (LAMC1, LUM, and LGALS1), invasion (GRB2 and RALB) and syncytialization (ANXA5 and ANXA1). We also identified multiple pre-eclampsia associated genes which are differentially expressed in Homo sapiens when compared to the other 13 species. Multiple genes are significantly associated with placenta morphology, including EREG and WNT5A which are both associated with placental shape.

Discussion: 115 genes are important for the core functions of the placenta in all eutherian species analyzed. The molecular functions and pathways enriched in the core placenta align with the evolutionarily conserved functionality of the placenta.

Keywords: Evolution; Gene expression; Mammal; Placenta; RNA-Seq.

Figure 1

Species tree for organisms studied showing the relationship between species. Branch lengths are not to scale. Silhouettes of species were obtained from http://phylopic.org.

Figure 2

Core Placenta Transcriptome. 115 ortholog pairs of Homo sapiens genes expressed (FPKM≥ 10) in the placenta of all 13 eutherians studied with housekeeping genes [32] removed ordered (from top to bottom, left to right) by median expression. If we also require expression (FPKM≥ 10) in the marsupial, Monodelphis domestica, there are 95 genes which meet this criteria. Figure 3 shows the shape of the distribution of the number of genes in the core placenta transcriptome if different FPKM and species restriction criteria are utilized.

Figure 3

Distribution shape of placenta core genes for all possible number of genes. The vertical axis shows the number of ortholog pairs included in the core placenta transcriptome (for all possible number of genes) if all 13 eutherians (or 14 of 14 species, or 13 of 14 species, etc.) have a minimum expression in FPKM equal to the horizontal axis. For example, if the cutoff is set to 10 (vertical black line), 115 genes would be included if the expression of a set of ortholog pairs of all 13 Eutherians must be at 9 least 10 FPKM, 271 ortholog pairs would be included if 13 of 14 species have an expression of at least 10 FPKM, and 937 genes would be included if 10 of 14 species must have an FPKM of at least 10.