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1.
Science ; 363(6422): 81-84, 2019 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-30606845

RESUMEN

Evolution generates a remarkable breadth of living forms, but many traits evolve repeatedly, by mechanisms that are still poorly understood. A classic example of repeated evolution is the loss of pelvic hindfins in stickleback fish (Gasterosteus aculeatus). Repeated pelvic loss maps to recurrent deletions of a pelvic enhancer of the Pitx1 gene. Here, we identify molecular features contributing to these recurrent deletions. Pitx1 enhancer sequences form alternative DNA structures in vitro and increase double-strand breaks and deletions in vivo. Enhancer mutability depends on DNA replication direction and is caused by TG-dinucleotide repeats. Modeling shows that elevated mutation rates can influence evolution under demographic conditions relevant for sticklebacks and humans. DNA fragility may thus help explain why the same loci are often used repeatedly during parallel adaptive evolution.


Asunto(s)
Roturas del ADN de Doble Cadena , ADN/química , Repeticiones de Dinucleótido , Pelvis/anatomía & histología , Eliminación de Secuencia , Smegmamorpha/genética , Animales , Evolución Biológica , Elementos de Facilitación Genéticos , Proteínas de Peces/genética , Conformación de Ácido Nucleico , Smegmamorpha/anatomía & histología , Factores de Transcripción/genética
2.
Elife ; 72018 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-30499775

RESUMEN

Vertebrate pelvic reduction is a classic example of repeated evolution. Recurrent loss of pelvic appendages in sticklebacks has previously been linked to natural mutations in a pelvic enhancer that maps upstream of Pitx1. The sequence of this upstream PelA enhancer is not conserved to mammals, so we have surveyed a large region surrounding the mouse Pitx1 gene for other possible hind limb control sequences. Here we identify a new pelvic enhancer, PelB, that maps downstream rather than upstream of Pitx1. PelB drives expression in the posterior portion of the developing hind limb, and deleting the sequence from mice alters the size of several hind limb structures. PelB sequences are broadly conserved from fish to mammals. A wild stickleback population lacking the pelvis has an insertion/deletion mutation that disrupts the structure and function of PelB, suggesting that changes in this ancient enhancer contribute to evolutionary modification of pelvic appendages in nature.


Asunto(s)
Evolución Biológica , Elementos de Facilitación Genéticos , Factores de Transcripción Paired Box/genética , Pelvis/crecimiento & desarrollo , Vertebrados/crecimiento & desarrollo , Vertebrados/genética , Animales , Secuencia de Bases , Cromosomas Artificiales Bacterianos/metabolismo , Secuencia Conservada , Peces/embriología , Regulación del Desarrollo de la Expresión Génica , Sitios Genéticos , Genoma , Miembro Posterior/crecimiento & desarrollo , Lagartos/embriología , Ratones , Factores de Transcripción Paired Box/metabolismo , Eliminación de Secuencia
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