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Lynch, V. J. et al. Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals. Proc. Natl Acad. Sci. USA 105, 14928-14933

Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 10/2008; 105(39):14928-33. DOI: 10.1073/pnas.0802355105
Source: PubMed

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.

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    • "Thus the relatively large average size (King and Wilson 1975; Tuch et al. 2008) and low pleiotropy of mutations in cis-regulatory regions may explain how with fewer mutations these structures can contribute substantially to phenotypic evolution. It is probable that genetic adaptation involves a combined effect of protein-coding and cis-regulatory changes (Hanikenne et al. 2008; Lynch et al. 2008; Tuch et al. 2008). For example, after gene duplication and subfunctionalization, protein-coding mutations could fine-tune some protein function and cis-regulatory mutations could specify regulatory expression for this function (Zhang 2003). "
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    • "We found no expression in chicken or opossum, but strong expression in elephant. Since the most recent common ancestor of humans and elephants is also the most recent common ancestor of all placental mammals, the most parsimonious interpretation of our data was that Prl expression at the MFI is a shared derived (synapomorphic) character of all placental mammals (Lynch et al. 2008). However, since the TSS of the human and macaque Prl transcript at the MFI is derived from a lineage-specific transposable element, the question arose: what is the mechanism of Prl expression in species that lack MER39? "
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