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From PPROM to caul: The evolution of membrane rupture in mammals ☆

View Article: PubMed Central - PubMed

ABSTRACT

Rupture of the extraembryonic membranes that form the gestational sac in humans is a typical feature of human parturition. However, preterm premature rupture of membranes (PPROM) occurs in approximately 1% of pregnancies, and is a leading cause of preterm birth. Conversely, retention of an intact gestational sac during parturition in the form of a caul is a rare occurrence. Understanding the molecular and evolutionary underpinnings of these disparate phenotypes can provide insight into both normal pregnancy and PPROM. Using phylogenetic techniques we reconstructed the evolution of the gestational sac phenotype at parturition in 55 mammal species representing all major viviparous mammal groups. We infer the ancestral state in therians, eutherians, and primates, as in humans, is a ruptured gestational sac at parturition. We present evidence that intact membranes at parturition have evolved convergently in diverse mammals including horses, elephants, and bats. In order to gain insight into the molecular underpinnings of the evolution of enhanced membrane integrity we also used comparative genomics techniques to reconstruct the evolution of a subset of genes implicated in PPROM, and find that four genes (ADAMTS2, COL1A1, COL5A1, LEPRE1) show significant evidence of increased nonsynonymous rates of substitution on lineages with intact membranes as compared to those with ruptured membranes. Among these genes, we also discovered that 17 human SNPs are associated with or near amino acid replacement sites in those mammals with intact membranes. These SNPs are candidate functional variants within humans, which may play roles in both PPROM and/or the retention of the gestational sac at birth.

No MeSH data available.


Related in: MedlinePlus

Adaptive evolution in COL1A2. Phylogenetic tree of mammals used in this study with COL1A2 branch-specific dN/dS above each branch, N*dN and S*dS values below each branch. COL1A2 shows evidence of adaptive evolution (dN/dS > 1.0) on three branches highlighted in red. Names of each species are colored with blue for intact gestational sac, green for partial gestational sac, and black for ruptured gestational sac. Abbreviations: dN/dS = ratio of non synonymous substitution rate/synonymous substitution rate; N*dN = nonsynonymous changes; S*dS = synonymous changes.
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f0015: Adaptive evolution in COL1A2. Phylogenetic tree of mammals used in this study with COL1A2 branch-specific dN/dS above each branch, N*dN and S*dS values below each branch. COL1A2 shows evidence of adaptive evolution (dN/dS > 1.0) on three branches highlighted in red. Names of each species are colored with blue for intact gestational sac, green for partial gestational sac, and black for ruptured gestational sac. Abbreviations: dN/dS = ratio of non synonymous substitution rate/synonymous substitution rate; N*dN = nonsynonymous changes; S*dS = synonymous changes.

Mentions: Using the free-ratio model, adaptive evolution can be detected within individual branches in the phylogenetic tree used in the analysis. One gene, COL1A2, showed clear evidence for adaptive evolution, (i.e. dN/dS > 1.0) on three branches, all within the Laurasiatheria (Fig. 3). These three branches are the stem branch of Carnivora, the stem branch of both the Perissodactyla and Cetartiodactyla, and the stem branch of Cetruminantia (cow and dolphin in the present study). Of the eight analyzed extant species included within these adaptively evolving clades, four are born with intact membranes and four are born with ruptured membranes. Free-ratio values for the remaining nine analyzed genes are provided in Supplemental Table 3. Five of these genes (COL3A1, CRTAP, LEPRE1, PLOD1, and ZMPSTE24) have limited evidence for positive selection but are not discussed here as dS = 0 on these branches.


From PPROM to caul: The evolution of membrane rupture in mammals ☆
Adaptive evolution in COL1A2. Phylogenetic tree of mammals used in this study with COL1A2 branch-specific dN/dS above each branch, N*dN and S*dS values below each branch. COL1A2 shows evidence of adaptive evolution (dN/dS > 1.0) on three branches highlighted in red. Names of each species are colored with blue for intact gestational sac, green for partial gestational sac, and black for ruptured gestational sac. Abbreviations: dN/dS = ratio of non synonymous substitution rate/synonymous substitution rate; N*dN = nonsynonymous changes; S*dS = synonymous changes.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121252&req=5

f0015: Adaptive evolution in COL1A2. Phylogenetic tree of mammals used in this study with COL1A2 branch-specific dN/dS above each branch, N*dN and S*dS values below each branch. COL1A2 shows evidence of adaptive evolution (dN/dS > 1.0) on three branches highlighted in red. Names of each species are colored with blue for intact gestational sac, green for partial gestational sac, and black for ruptured gestational sac. Abbreviations: dN/dS = ratio of non synonymous substitution rate/synonymous substitution rate; N*dN = nonsynonymous changes; S*dS = synonymous changes.
Mentions: Using the free-ratio model, adaptive evolution can be detected within individual branches in the phylogenetic tree used in the analysis. One gene, COL1A2, showed clear evidence for adaptive evolution, (i.e. dN/dS > 1.0) on three branches, all within the Laurasiatheria (Fig. 3). These three branches are the stem branch of Carnivora, the stem branch of both the Perissodactyla and Cetartiodactyla, and the stem branch of Cetruminantia (cow and dolphin in the present study). Of the eight analyzed extant species included within these adaptively evolving clades, four are born with intact membranes and four are born with ruptured membranes. Free-ratio values for the remaining nine analyzed genes are provided in Supplemental Table 3. Five of these genes (COL3A1, CRTAP, LEPRE1, PLOD1, and ZMPSTE24) have limited evidence for positive selection but are not discussed here as dS = 0 on these branches.

View Article: PubMed Central - PubMed

ABSTRACT

Rupture of the extraembryonic membranes that form the gestational sac in humans is a typical feature of human parturition. However, preterm premature rupture of membranes (PPROM) occurs in approximately 1% of pregnancies, and is a leading cause of preterm birth. Conversely, retention of an intact gestational sac during parturition in the form of a caul is a rare occurrence. Understanding the molecular and evolutionary underpinnings of these disparate phenotypes can provide insight into both normal pregnancy and PPROM. Using phylogenetic techniques we reconstructed the evolution of the gestational sac phenotype at parturition in 55 mammal species representing all major viviparous mammal groups. We infer the ancestral state in therians, eutherians, and primates, as in humans, is a ruptured gestational sac at parturition. We present evidence that intact membranes at parturition have evolved convergently in diverse mammals including horses, elephants, and bats. In order to gain insight into the molecular underpinnings of the evolution of enhanced membrane integrity we also used comparative genomics techniques to reconstruct the evolution of a subset of genes implicated in PPROM, and find that four genes (ADAMTS2, COL1A1, COL5A1, LEPRE1) show significant evidence of increased nonsynonymous rates of substitution on lineages with intact membranes as compared to those with ruptured membranes. Among these genes, we also discovered that 17 human SNPs are associated with or near amino acid replacement sites in those mammals with intact membranes. These SNPs are candidate functional variants within humans, which may play roles in both PPROM and/or the retention of the gestational sac at birth.

No MeSH data available.


Related in: MedlinePlus