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Evolutionary BiologybioRxiv
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HP6/Umbrea, a rapidly evolving Drosophila HP1-family paralog, is a candidate HP1a-recruited plasticizer of heterochromatin

UnJin LeeiD, Li ZhaoiD

Abstract

HP6/Umbrea, a rapidly evolving Drosophila (Heterochromatin Protein 1) HP1-family paralog, has well-documented sequence and regulatory evolution but an under-studied molecular function. In this manuscript, we hypothesize that HP6/Umbrea acts as an HP1-recruited plasticizer, providing support for this model using coarse-grained molecular-dynamics simulations of HP1a condensates. Retaining only the dimerizing chromoshadow domain (CSD), HP6/Umbrea notably lacks independent chromatin-binding capacity but binds HP1a directly, co-localizing with it in vivo. We report that when covalently tethered to an HP1a carrier, HP6/Umbrea partitions into HP1a condensates ~6-fold more strongly than when free, supporting HP1a-mediated recruitment as its entry route. Once incorporated, HP6/Umbrea leaves the phase-separation threshold, interfacial tension, and host partitioning statistically unchanged, but monotonically lowers dense-phase density. These observations are consistent with a spacer function rather than generic loss of cohesion. Importantly, unchanged short-time internal mobility suggests a packing effect, predicting increased permeability to large transcriptional machinery, potentially resulting in a position effect-variegation (PEV)-like modulation of heterochromatic silencing. Finally, comparative sequence analysis shows the C-terminal tail is a recently originated, purifying-selection-constrained innovation, which is consistent with an evolved function in this region. In sum, our simulations suggest a mechanistic basis for how HP6/Umbrea may have evolved as a condensate plasticizer and thus potentially act as a rheostat for leaky transcription.

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02 /Specification & Classification

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