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Advancing human disease research with fish evolutionary mutant models

2021; Elsevier BV; Volume: 38; Issue: 1 Linguagem: Inglês

10.1016/j.tig.2021.07.002

1362-4555

Emily A. Beck, Hope M. Healey, Clayton M. Small, Mark Currey, Thomas Desvignes, William A. Cresko, John H. Postlethwait,

Aquaculture disease management and microbiota

Some animals evolved natural phenotypes that mimic human diseases but are not pathogenic in the animals’ specific environments. Understanding molecular genetic strategies that evolutionary mutant medical models use to compensate for their pathology-mimicking phenotypes can suggest new avenues for novel therapies. Understanding evolutionary mutant models illuminates the role of genetic variation in disease etiology. Technical advances in genomics and molecular biology facilitate the expansion of disease research to non-model organisms. The deep radiation of fish generated a kaleidoscope of specialized phenotypes that mechanistically mimic human disease. Here we describe seven fish EMMs used to tackle research on nine groups of human diseases. Model organism research is essential to understand disease mechanisms. However, laboratory-induced genetic models can lack genetic variation and often fail to mimic the spectrum of disease severity. Evolutionary mutant models (EMMs) are species with evolved phenotypes that mimic human disease. EMMs complement traditional laboratory models by providing unique avenues to study gene-by-environment interactions, modular mutations in noncoding regions, and their evolved compensations. EMMs have improved our understanding of complex diseases, including cancer, diabetes, and aging, and illuminated mechanisms in many organs. Rapid advancements of sequencing and genome-editing technologies have catapulted the utility of EMMs, particularly in fish. Fish are the most diverse group of vertebrates, exhibiting a kaleidoscope of specialized phenotypes, many that would be pathogenic in humans but are adaptive in the species’ specialized habitat. Importantly, evolved compensations can suggest avenues for novel disease therapies. This review summarizes current research using fish EMMs to advance our understanding of human disease. Model organism research is essential to understand disease mechanisms. However, laboratory-induced genetic models can lack genetic variation and often fail to mimic the spectrum of disease severity. Evolutionary mutant models (EMMs) are species with evolved phenotypes that mimic human disease. EMMs complement traditional laboratory models by providing unique avenues to study gene-by-environment interactions, modular mutations in noncoding regions, and their evolved compensations. EMMs have improved our understanding of complex diseases, including cancer, diabetes, and aging, and illuminated mechanisms in many organs. Rapid advancements of sequencing and genome-editing technologies have catapulted the utility of EMMs, particularly in fish. Fish are the most diverse group of vertebrates, exhibiting a kaleidoscope of specialized phenotypes, many that would be pathogenic in humans but are adaptive in the species’ specialized habitat. Importantly, evolved compensations can suggest avenues for novel disease therapies. This review summarizes current research using fish EMMs to advance our understanding of human disease. the presence of DNA from individuals of distantly related, formerly genetically isolated populations, resulting from interbreeding. a noncoding genomic region identified by sequence conservation among multiple species. genetic polymorphisms that interact to produce joint, non-additive effects on phenotypes. genomic loci that are correlated with variation of expression levels of transcripts. changes in the relative frequency of alleles in a population due to chance. nonrandom association of alleles from different loci. gene duplicates created by a whole-genome duplication event. genes in different species that evolved from a single gene in the last common ancestor. genomic loci that correlate with an observed quantitative trait. a family of teleost fishes, including seahorses, pipefishes, and seadragons, characterized by an elongated snout and male pregnancy. ray-finned fish that have a dorso-ventrally symmetrical tail fin, in contrast to basally diverging ray-finned fish like their sister group, the Holostei (bowfins and garfish), and more basally diverging fish, like Chondrostei (sturgeons and redfish), that have asymmetrical tail fins.