Phylogenetic profiling resolves early emergence of PRC2 and illuminates its functional core

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Genomics

Background:

• Polycomb repressive complex 2 (PRC2) epigenetically silences genes by methylating histone H3 lysine 27.
• The catalytic subunit, enhancer of zeste [E(z)], is crucial for PRC2 function.
• Understanding PRC2 subunit evolution across eukaryotes provides insights into chromatin regulation.

Purpose of the Study:

• To investigate the evolutionary diversity and molecular evolution of PRC2 core subunits in eukaryotes.
• To identify the evolutionary origins of PRC2, particularly in early-diverged lineages.
• To explore the conservation and variation of PRC2 subunits, including E(z), ESC, and Su(z)12.

Main Methods:

• Phylogenetic analysis of PRC2 core subunit proteins across 283 eukaryotic species.
• Identification of putative orthologs, focusing on early-diverged lineages like Discoba.
• Bioinformatic analysis including SET-domain and H3 histone interaction prediction.

Main Results:

• The putative ortholog of E(z) was identified in Discoba, suggesting PRC2 predates eukaryotic diversification.
• E(z) and ESC are commonly present across analyzed species, indicating a conserved functional core.
• Full-length Su(z)12 orthologs were not universally detected, implying high divergence, functional convergence, or dispensability.

Conclusions:

• PRC2 likely emerged before the diversification of eukaryotes, with E(z) and ESC forming a conserved core.
• The variable presence of Su(z)12 suggests evolutionary plasticity in PRC2 complex composition.
• E(z) evolution within the SET-domain family may involve substrate specificity shifts impacting H3 histone interactions.