DNA fragility in the parallel evolution of pelvic reduction in threespine stickleback fish (Gasterosteus aculeatus)

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Abstract/Contents

Abstract
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 limbs in stickleback fish (Gasterosteus aculeatus). Repeated pelvic loss has been mapped to independent deletions of a pelvic enhancer upstream of Pitx1, an essential transcription factor. Here, we identify molecular features that contribute to this unusual spectrum of adaptive deletions. We find that Pitx1 enhancer sequences form non-canonical DNA structures in vitro and increase DNA double-strand breaks ~50-100 times in vivo. The fragility of the enhancer also depends on DNA replication direction and is caused by (TG)-dinucleotide repeats. Modeling shows that high mutation rates aid evolution under widespread demographic conditions, including those relevant for sticklebacks and humans. Our results suggest that DNA fragility is an important mechanism for generating adaptive alleles in natural populations.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2017
Issuance monographic
Language English

Creators/Contributors

Associated with Xie, Kathleen Tian
Associated with Stanford University, Department of Biochemistry.
Primary advisor Kingsley, David M. (David Mark)
Thesis advisor Kingsley, David M. (David Mark)
Thesis advisor Herschlag, Daniel
Thesis advisor Krasnow, Mark, 1956-
Advisor Herschlag, Daniel
Advisor Krasnow, Mark, 1956-

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Kathleen Tian Xie.
Note Submitted to the Department of Biochemistry.
Thesis Thesis (Ph.D.)--Stanford University, 2017.
Location electronic resource

Access conditions

Copyright
© 2017 by Kathleen Tian Xie
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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