A fast-evolving human NPAS3 enhancer gained reporter expression in the developing forebrain of transgenic mice.
The developmental brain gene NPAS3 stands out as a hot spot in human evolution because it contains the largest number of human-specific, fast-evolving, conserved, non-coding elements. In this paper we studied 2xHAR142, one of these elements that is located in the fifth intron of NPAS3. Using transgenic mice, we show that the mouse and chimp 2xHAR142 orthologues behave as transcriptional enhancers driving expression of the reporter gene lacZ to a similar NPAS3 expression subdomain in the mouse central nervous system. Interestingly, the human 2xHAR142 orthologue drives lacZ expression to an extended expression pattern in the nervous system. Thus, molecular evolution of 2xHAR142 provides the first documented example of human-specific heterotopy in the forebrain promoted by a transcriptional enhancer and suggests that it may have contributed to assemble the unique properties of the human brain.
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), , Buenos Aires, Argentina.
Gretel B
GB
Kamm
Rodrigo
R
López-Leal
Juan R
JR
Lorenzo
Lucía F
LF
Franchini
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D019143:Evolution, Molecular; D005697:Galactosides; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007211:Indoles; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D002679:Pan troglodytes / Q000235:genetics; D016548:Prosencephalon / Q000378:metabolism*; D020086:Short Interspersed Nucleotide Elements / Q000235:genetics; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D005697:Galactosides; D007211:Indoles; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C502963:NPAS3 protein, human; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside
MIR; NPAS3; brain; evolution; exaptation; schizophrenia