bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.05.20.595041

Segregation between an ornamental and a disease driver gene provides insights into pigment cell regulation

Abstract

Genetic interactions are adaptive within a species. Hybridization can disrupt such species-specific genetic interactions and creates novel interactions that alter the hybrid progeny overall fitness. Hybrid incompatibility, which refers to degenerative genetic interactions that decrease the overall hybrid survival, is one of the results from combining two diverged genomes in hybrids. The discovery of spontaneous lethal tumorigenesis and underlying genetic interactions in select hybrids between diverged Xiphophorus species showed that lethal pathological process can result from degenerative genetic interactions. Such genetic interactions leading to lethal phenotype are thought to shield gene flow between diverged species. However, hybrids between certain Xiphophorus species do not develop such tumors. Here we report the identification of a locus residing in the genome of one Xiphophorus species that represses an oncogene from a different species. Our finding provides insights into normal and pathological pigment cell development, regulation and molecular mechanism in hybrid incompatibility. SignificanceThe Dobzhansky-Muller model states epistatic interactions occurred between genes in diverged species underlies hybrid incompatibility. There are a few vertebrate interspecies hybrid cases that support the Dobzhansky-Muller model. This study reports a fish hybrid system where incompatible genetic interactions are involved in neuronal regulation of pigment cell biology, and also identified a novel point of regulation for pigment cells.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Soria, E., Lu, Q., Boswell, W., Du, K., Xing, Y., Boswell, M., Weldon, K., Lai, Z., Savage, M., Schartl, M., Lu, Y.. 2024-05-22. Segregation between an ornamental and a disease driver gene provides insights into pigment cell regulation. https://doi.org/10.1101/2024.05.20.595041

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Genetic ancestry influences the relative expression of ancestral haplotypes within admixed individuals

Allele-specific expression (ASE) reflects differences between the two haplotypes a person carries, but most ASE studies have been done in European-descent samples. Admixed individuals carry haplotypes from different ancestral backgrounds within the same cell, which allows ancestry effects on regulation to be measured directly. We integrated phased whole-blood RNA-seq with local ancestry inference in 779 participants from the MAGENTA cohort, including non-Hispanic White, African American, Caribbean Hispanic, and Peruvian individuals. Higher West African (YRI) ancestry proportion was associated with more ASE-positive genes per person, and the association remained after adjusting for age, sex, Alzheimer's disease status, APOE genotype, and the number of heterozygous genes. Peruvian ancestry showed no significant association. A gene-level test of imbalance across population groups found 2,053 of 15,008 genes with significant differences, including the major histocompatibility complex in all four groups. A genome-wide scan of 2,213 1 Mb windows compared people carrying two haplotypes of different ancestries with those carrying two of the same ancestry. It identified 52 non-redundant loci that replicated across all four population groups, containing 201, 60, and 110 ancestry-associated genes under the CEU, YRI, and PEL reference baselines. A haplotype-resolved directional analysis showed no genome-wide advantage for either ancestry. It found locus-specific dominance at 11 loci, and only chr8:2-3 Mb (CSMD1) showed the same direction in more than one population group. Genetic ancestry therefore shapes allelic regulation at global, gene, and locus scales.

genetics↗

Assembly-independent measurement of human Yq12 heterochromatin reveals population-scale variation and Yq12-derived RNA in testis

Despite advances in long-read sequencing and telomere-to-telomere assembly, population-scale analysis of large satellite arrays remains challenging. Human Yq12 is a megabase-scale heterochromatic region composed primarily of DYZ1/HSat3A6 and DYZ2/HSat1B repeats, whose near-equal proportions are maintained despite extensive variation in total array length. Here, using complete Y-chromosome assemblies, we developed k-mer-based tools to estimate Yq12 size directly from short- and long-read sequencing data without requiring sample-specific complete assemblies. Across 1,597 males from the 1000 Genomes Project, Yq12 length ranged from ~1 to 52 Mb (mean 26.5 Mb) and varied substantially within and between Y haplogroups. Phylogenetic analyses supported long-term constraint of total Yq12 length near an equilibrium of 26 Mb and strongly coupled evolution of DYZ1 and DYZ2 around near-parity composition. In 303 father-son pairs, fathers had longer estimated Yq12 regions in 70.6% of pairs, while sons more often showed DYZ1:DYZ2 ratios closer to 1:1. Testis Iso-Seq identified transcripts containing DYZ1 and DYZ2 satellite sequences, while single-cell RNA-seq revealed their expression in haploid spermatids. These results establish a scalable framework for studying Yq12 population variation, intergenerational dynamics, and transcription, providing new opportunities to investigate how extreme satellite-array variation relates to Y-chromosome evolution and male germ-cell biology.

genetics↗

Continuous ancestry profiles from genomes and genealogies

Using a single population label to represent an individual's ancestry may offer convenience, but ancestry is multidimensional, continuous, and reflects contributions from multiple ancestral sources. Here, we demonstrate empirically that ancestry profiles outperform categorical ancestry labels in capturing this complexity. Relatedness among 28,332 genotyped individuals was measured using haplotype painting and ordination and was regressed on regional ancestry proportions from the deep genealogies available for one-third of the cohort. When tested on participants in a validation set, predicted profiles placed 78% of documented ancestry in the correct region, against 48% for the training set average. Giving each participant a single regional label placed only 32% of their documented ancestry correctly, and a perfect classifier naming each person's largest documented region would reach only 38%, because most individuals carry ancestry from several regions. Thus, the continuous profile captures substantially more ancestry than any classification, providing support for representing ancestry as a continuum rather than a label.

genetics↗