Titel
Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals
Autor*in
Vincent J. Lynch
Yale University
Autor*in
Yajun Wang
University of Hong Kong
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Abstract
Evolutionary change in gene regulation can result from changes in cis-regulatory elements, leading to differences in the temporal and spatial expression of genes or in the coding region of transcription factors leading to novel functions or both. Although there is a growing body of evidence supporting the importance of cis-regulatory evolution, examples of protein-mediated evolution of novel developmental pathways have not been demonstrated. Here, we investigate the evolution of prolactin (PRL) expression in endometrial cells, which is essential for placentation/pregnancy in eutherian mammals and is a direct regulatory target of the transcription factor HoxA-11. Here, we show that (i) endometrial PRL expression is a derived feature of placental mammals, (ii) the PRL regulatory gene HoxA-11 experienced a period of strong positive selection in the stem-lineage of eutherian mammals, and (iii) only HoxA-11 proteins from placental mammals, including the reconstructed ancestral eutherian gene, are able to up-regulate PRL from the promoter used in endometrial cells. In contrast, HoxA-11 from the reconstructed therian ancestor, opossum, platypus, and chicken are unable to up-regulate PRL expression. These results demonstrate that the evolution of novel gene expression domains is not only mediated by the evolution of cis-regulatory elements but can also require evolutionary changes of transcription factor proteins themselves.
Objekt-Typ
Sprache
Englisch [eng]
Erschienen in
Titel
Proceedings of the National Academy of Sciences of the United States of America (PNAS)
Band
105
Ausgabe
39
Seitenanfang
14928
Seitenende
14933
Erscheinungsdatum
01.01.2008
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