Mapping vertebrate incompatibility alleles: Deleterious gene interactions may underlie the observed hybrid incompatibilities. However, few genes underlying hybrid incompatibilities have been identified, and most of these involve species that do not hybridize in natural conditions. Powell et al. used genome sequencing to map genes likely responsible for incompatibilities that reduce fitness in naturally occurring hybrid swordtail fish. These gene combinations result in malignant melanoma, which is found in naturally hybridizing populations but is not present in the parental populations (see the Perspective by Dagilis and Matute). Using genome and population resequencing, the authors performed a genome-wide association study to identify potentially causative mutations. Using an admixture mapping approach that assessed introgression between multiple swordtail fish species, the authors suggest that lineages carry different genes that interact with the same candidate gene, resulting in the observed melanomas and providing insight into convergent hybrid incompatibles that arise between species. Science , this issue p. 731 ; see also p. 710

Mechanisms of sex chromosome dosage compensation (SCDC) differ strikingly among animals. In Drosophila flies, chromosome-wide transcription is doubled from the single X chromosome in hemizygous (XY) males, whereas in Caenorhabditis nematodes, expression is halved for both X copies in homozygous (XX) females [1, 2]. Unlike other female-heterogametic (WZ female and ZZ male) animals, moths and butterflies exhibit sex chromosome dosage compensation patterns typically seen only in male-heterogametic species [3]. The monarch butterfly carries a newly derived Z chromosome segment that arose from an autosomal fusion with the ancestral Z [4]. Using a highly contiguous genome assembly, we show that gene expression is balanced between sexes along the entire Z chromosome but with distinct modes of compensation on the two segments. On the ancestral Z segment, depletion of H4K16ac corresponds to nearly halving of biallelic transcription in males, a pattern convergent to nematodes. Conversely, the newly derived Z segment shows a Drosophila-like mode of compensation, with enriched H4K16ac levels corresponding to doubled monoallelic transcription in females. Our work reveals that, contrary to the expectation of co-opting regulatory mechanisms readily in place, the evolution of plural modes of dosage compensation is also possible along a single sex chromosome within a species.

Previous evolutionary models of duplicate gene evolution have overlooked the pivotal role of genome architecture. Here, we show that proximity-based regulatory recruitment by distally duplicated genes is an efficient mechanism for modulating tissue-specific production of preexisting proteins. By leveraging genomic asymmetries, we performed a coexpression analysis on Drosophila melanogaster tissue data to show the generality of enhancer capture-divergence (ECD) as a significant evolutionary driver of asymmetric, distally duplicated genes. We use the recently evolved gene HP6 / Umbrea as an example of the ECD process. By assaying genome-wide chromosomal conformations in multiple Drosophila species, we show that HP6/Umbrea was inserted near a preexisting, long-distance three-dimensional genomic interaction. We then use this data to identify a newly found enhancer ( FLEE1 ), buried within the coding region of the highly conserved, essential gene MFS18 , that likely neofunctionalized HP6/Umbrea . Last, we demonstrate ancestral transcriptional coregulation of HP6/Umbrea ’s future insertion site, illustrating how enhancer capture provides a highly evolvable, one-step solution to Ohno’s dilemma.

Near Oceanic populations harbor substantial cultural, phenotypic, and genetic diversity yet are drastically underrepresented in human genomics. We generated 177 high-coverage Near Oceanian whole genomes and analyzed them alongside 1284 worldwide genomes, revealing major distinctions among and within islands, including long-term isolation and strong population bottlenecks. We reconstructed 1.897 billion base pairs of the archaic genome, including 831.9 million base pairs of Denisovan sequence, and found evidence for introgression from three Denisovan-like groups in Near Oceanians and adaptive Denisovan introgression at TRPS1 , a skeletal development gene also under selection in central African rainforest hunter-gatherers and highland Ecuadorians. We then performed a massively parallel reporter assay and discovered 3127 high-frequency introgressed expression-modulating variants, finding an enrichment of functional impacts on genes in the interferon-γ signaling pathway including JAK1 , GBP2 , and OAS1 .