A rapidly evolving genomic toolkit for Drosophila heterochromatin

Abstract

Heterochromatin is the enigmatic eukaryotic genome compartment found mostly at telomeres and centromeres. Conventional approaches to sequence assembly and genetic manipulation fail in this highly repetitive, gene-sparse, and recombinationally silent DNA. In contrast, genetic and molecular analyses of euchromatin-encoded proteins that bind, remodel, and propagate heterochromatin have revealed its vital role in numerous cellular and evolutionary processes. Utilizing the 12 sequenced Drosophila genomes, Levine et al (1) took a phylogenomic approach to discover new such protein "surrogates" of heterochromatin function and evolution. This paper reported over 20 new members of what was traditionally believed to be a small and static Heterochromatin Protein 1 (HP1) gene family. The newly identified HP1 proteins are structurally diverse, lineage-restricted, and expressed primarily in the male germline. The birth and death of HP1 genes follows a "revolving door" pattern, where new HP1s appear to replace old HP1s. Here, we address alternative evolutionary models that drive this constant innovation.

Keywords: Drosophila; HP1; Heterochromatin Protein 1; chromodomain; chromoshadow domain; gene duplication; germline; heterochromatin; phylogenomics; pseudogenization.

Figure 1. (A) Canonical HP1 domain structure. The chromodomain (”chromo”) recognizes H3K9me, the hinge binds DNA and/or RNA, and the chromoshadow (”shadow”) homodimerizes and heterodimerizes. (B) Alternative paths underlying half-HP1 birth. Drift or selection drives the degeneration of the chromodomain (in this example) following a full HP1 duplication event. Alternatively, the duplication itself is restricted to a single domain. A 3′ retrotransposition bias may underlie the enrichment of chromoshadow domain-only HP1s observed in our data set.

Figure 2. Revolving door dynamics: gene number stasis, recurrent birth, and recurrent death. The 10 chromoshadow-only genes represented are all expressed primarily in testis. Each lineage harbors either two or three HP1s of this domain class, but these genes are rarely shared across distant lineages. ● Expression assayed directly by tissue-restricted RTPCR. ● Expression inferred.

Figure 3. Alternative forces driving gene replacements. (A) Birth and then fixation/death under neutral forces. (B) Birth and then fixation under neutral forces or positive selection, death driven by negative selection to relieve dosage effects, such as heterochromatin expansion/contraction or positive/negative transcriptional regulation.^- (C) Birth and then fixation under positive selection to suppress recurrently evolving selfish elements, death under neutral forces. “p” = parent gene, “d” = daughter gene.