11Beta-hydroxysteroid dehydrogenase-type 2 evolved from an ancestral 17beta-hydroxysteroid dehydrogenase-type 2

Area of Science:

• Biochemistry
• Evolutionary Biology
• Genomics

Background:

• 11beta-hydroxysteroid dehydrogenase-type 2 (11beta-HSD2) and 17beta-HSD2 are paralogous enzymes regulating steroid hormone concentrations.
• These enzymes are crucial for activating glucocorticoid, mineralocorticoid, androgen, and estrogen receptors.
• The evolutionary origins and divergence of 11beta-HSD2 and 17beta-HSD2 remain largely unknown.

Purpose of the Study:

• To investigate the evolutionary origins and early divergence of 11beta-HSD2 and 17beta-HSD2.
• To utilize genomic data from basal deuterostomes and chordates to trace the evolutionary history of these enzymes.

Main Methods:

• Bioinformatic analyses, including BLAST searches, were performed on genomic sequences from sea urchin, acorn worm, amphioxus, and elephant shark.
• Phylogenetic analyses were conducted to infer the evolutionary relationships and identify ancestral sequences.

Main Results:

• An ancestral 17beta-HSD2 sequence was identified in early deuterostomes (sea urchin, acorn worm, amphioxus).
• An ancestral 11beta-HSD2 sequence was first detected in sharks, indicating a later evolutionary appearance.
• Sequence analyses suggest potential non-enzymatic activity for sea urchin 17beta-HSD2 and novel substrate metabolism for acorn worm 17beta-HSD2 if catalytically active.

Conclusions:

• 17beta-HSD2 likely predates 11beta-HSD2, with its origins traceable to early deuterostomes.
• The emergence of 11beta-HSD2 appears to have occurred later in vertebrate evolution, specifically by the shark lineage.
• Early 17beta-HSD2 enzymes may have possessed different functional properties, including potential non-enzymatic roles or novel substrate specificities.