title: Dispersal of an ancient retroposon in the TP53 promoter of Bovidae: phylogeny, novel mechanisms, and potential implications for cow milk persistency.
abstract: BACKGROUND
  In recent years, the perception of transposable genetic elements has changed from "junk DNA" to a focus of interest when appearing near or inside genes. Bov-A2 is a short interspersed nuclear element (SINE) that was first found in Bovidae and later in other ruminants. This retroposon is mostly used as a marker for phylogenetic analysis.
  
  
  RESULTS
  We describe insertions of Bov-A2 in the promoter region of TP53, a key tumor suppressor gene that is indispensable for diverse developmental processes, in Antilopinae and Tragelaphini (belonging to the Bovinae subfamily). In Tragelaphini two Bov-A2 elements were inserted sequentially, whereas in 5 tribes of Antilopinae only one Bov-A2 element was inserted, in a different site and reverse orientation. The entrance site in both cases employed short palindromes that can form hairpin secondary structures. Interestingly, mutations that create or disrupt base pairing in the palindrome sequence dictated the presence or absence of Bov-A2, such as in the domestic cow and buffalo, which lack Bov-A2. Transcription factor binding site analysis revealed unique binding sites for STAT3 and NFκB within the Bov-A2 sequence, which together with TP53 itself are known to play a crucial role in mammary involution.
  
  
  CONCLUSIONS
  This report demonstrates how short palindromes serve as hot spots for Bov-A2 retroposon insertion into the mammalian genome. The strict correlation between point mutation in the palindromes and the presence/absence of Bov-A2 retroposon insertions, questions the use of singular insertion events as valid phylogenetic markers inside families. Bov-A2 insertion into the TP53 promoter in Antilopinae and Tragelaphini may not only provide a genetic network that regulates mammary involution, but can also answer the need for rapid mammary involution in Savanna antelopes after weaning, partially in response to predation stress. The absence of Bov-A2 in domestic bovids may constitute the molecular background for greater lactation persistency.
authors: MIGAL - Galilee Research Institute, Kiryat Shmona, Israel. yaron@gga.org.il.|Tel Hai College, Upper Galilee, Israel. yaron@gga.org.il.|Golan Research Institute, Katzrin, Israel. yaron@gga.org.il.
authors: Yaron
authors: Y
authors: Dekel
authors: Weizmann Institute of Science, Rehovot, Israel. Machluf.Yossy@weizmann.ac.il.
authors: Yossy
authors: Y
authors: Machluf
authors: Weizmann Institute of Science, Rehovot, Israel. shifra.ben-dor@weizmann.ac.il.
authors: Shifra
authors: S
authors: Ben-Dor
authors: Weizmann Institute of Science, Rehovot, Israel. oren.yifa@weizmann.ac.il.
authors: Oren
authors: O
authors: Yifa
authors: Tel Hai College, Upper Galilee, Israel. aviad@gga.org.il.
authors: Aviad
authors: A
authors: Stoler
authors: Faculty of Medicine in the Galilee, Bar Ilan University & Baruch Padeh Medical Center, Poria, & Zefat Academic College, Safed, Israel. izhar.benshlomo@gmail.com.
authors: Izhar
authors: I
authors: Ben-Shlomo
authors: Tel Hai College, Upper Galilee, Israel. dannyb@telhai.ac.il.
authors: Dani
authors: D
authors: Bercovich
mesh_terms: D000818:Animals; D002020:Buffaloes / Q000235:genetics; D002417:Cattle; D019143:Evolution, Molecular; D005260:Female; D053263:Gene Regulatory Networks / Q000235:genetics; D016678:Genome; D008892:Milk; D008969:Molecular Sequence Data; D010802:Phylogeny; D050796:STAT3 Transcription Factor / Q000235:genetics; D020086:Short Interspersed Nucleotide Elements / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D050796:STAT3 Transcription Factor; D016159:Tumor Suppressor Protein p53
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