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Cognitive Function Related to the Sirh11/Zcchc16 Gene Acquired from an LTR Retrotransposon in Eutherians.

Irie M, Yoshikawa M, Ono R, Iwafune H, Furuse T, Yamada I, Wakana S, Yamashita Y, Abe T, Ishino F, Kaneko-Ishino T - PLoS Genet. (2015)

Bottom Line: Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein.Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA) was reduced compared with dopamine (DA) after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO) mice.Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1.

View Article: PubMed Central - PubMed

Affiliation: School of Health Sciences, Tokai University, Isehara, Kanagawa, Japan; Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan.

ABSTRACT
Gene targeting of mouse Sushi-ichi-related retrotransposon homologue 11/Zinc finger CCHC domain-containing 16 (Sirh11/Zcchc16) causes abnormal behaviors related to cognition, including attention, impulsivity and working memory. Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein. Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA) was reduced compared with dopamine (DA) after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO) mice. These data indicate that Sirh11/Zcchc16 is involved in cognitive function in the brain, possibly via the noradrenergic system, in the contemporary mouse developmental systems. Interestingly, it is highly conserved in three out of the four major groups of the eutherians, euarchontoglires, laurasiatheria and afrotheria, but is heavily mutated in xenarthran species such as the sloth and armadillo, suggesting that it has contributed to brain evolution in the three major eutherian lineages, including humans and mice. Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1.

No MeSH data available.


Related in: MedlinePlus

Characteristics of Sirh11/Zcchc16.(A) Structure of the Sirh11/Zcchc16 protein. The scheme shows the alignment of the sushi-ichi gag domain and Sirh11/Zcchc16 proteins, which overall exhibit 21% identity and 37.5% similarity, respectively. The zinc finger CCHC domain (purple) in the C-terminus is conserved, but the coiled-coil motif (green) and gag domain (blue) are absent in the Sirh11/Zcchc16 protein. (B) Chromosomal Location. SIRH11/ZCCH16 is conserved in an orthologous chromosomal region between TRPC5 and LHFPL1 in eutherian mammals. The upper panel shows that SIRH11/ZCCHC16 is absent in the chicken (birds), platypus (monotremes) and opossum (marsupials). The identically colored boxes represent orthologous genes and the light blue boxes represent psuedoSIRH11/ZCCHC16 genes. The lower panel provides a comparison of SIRH11/ZCCHC16 and its flanking genome sequences with 50~100% homology to the mouse genome in several eutherian mammals. The purple (SIRH11/ZCCHC16) and red (others) areas indicate evolutionarily conserved sequences (ECSs). The shaded area indicates the regions that correspond to the mouse Sirh11/Zcchc16 open reading frame. The yellow line in the Armadillo column represents the gap region in the genome sequence. (C) Conservation of Sirh11/Zcchc16 in eutherian mammals. The SIRH11/ZCCHC16 sequence was confirmed in four major eutherian groups (red), euarchontoglires, laurasiatheria, xenarthra and afrotheria, but became a pseudogene in xenarthra (the dashed line), indicating that the insertion of SIRH11/ZCCHC16 occurred in a common eutherian ancestor. The number of species possessing SIRH11/ZCCHC16 (front) and those which in total were analyzed (back) are noted in parentheses. (D) PAML analysis. Two models, the one-ratio model based on the assumption that ω1 (dN/dS) is the same for all of the branches (model 1) and the two-ratio model based on the assumption that ω2 in the xenathran lineage is different from ω1 in all the others (model 2) were compared. The model 2 was statistically significant and is shown. The p-value was calculated by the likelihood ratio test. Armadillo 1 and 2 represent Dasypus novemcinctus and Tolypeutes matacus, respectively. Sloth 1 and 2 represent Choloepus hoffmanni and Choloepus didactylus, respectively.
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pgen.1005521.g001: Characteristics of Sirh11/Zcchc16.(A) Structure of the Sirh11/Zcchc16 protein. The scheme shows the alignment of the sushi-ichi gag domain and Sirh11/Zcchc16 proteins, which overall exhibit 21% identity and 37.5% similarity, respectively. The zinc finger CCHC domain (purple) in the C-terminus is conserved, but the coiled-coil motif (green) and gag domain (blue) are absent in the Sirh11/Zcchc16 protein. (B) Chromosomal Location. SIRH11/ZCCH16 is conserved in an orthologous chromosomal region between TRPC5 and LHFPL1 in eutherian mammals. The upper panel shows that SIRH11/ZCCHC16 is absent in the chicken (birds), platypus (monotremes) and opossum (marsupials). The identically colored boxes represent orthologous genes and the light blue boxes represent psuedoSIRH11/ZCCHC16 genes. The lower panel provides a comparison of SIRH11/ZCCHC16 and its flanking genome sequences with 50~100% homology to the mouse genome in several eutherian mammals. The purple (SIRH11/ZCCHC16) and red (others) areas indicate evolutionarily conserved sequences (ECSs). The shaded area indicates the regions that correspond to the mouse Sirh11/Zcchc16 open reading frame. The yellow line in the Armadillo column represents the gap region in the genome sequence. (C) Conservation of Sirh11/Zcchc16 in eutherian mammals. The SIRH11/ZCCHC16 sequence was confirmed in four major eutherian groups (red), euarchontoglires, laurasiatheria, xenarthra and afrotheria, but became a pseudogene in xenarthra (the dashed line), indicating that the insertion of SIRH11/ZCCHC16 occurred in a common eutherian ancestor. The number of species possessing SIRH11/ZCCHC16 (front) and those which in total were analyzed (back) are noted in parentheses. (D) PAML analysis. Two models, the one-ratio model based on the assumption that ω1 (dN/dS) is the same for all of the branches (model 1) and the two-ratio model based on the assumption that ω2 in the xenathran lineage is different from ω1 in all the others (model 2) were compared. The model 2 was statistically significant and is shown. The p-value was calculated by the likelihood ratio test. Armadillo 1 and 2 represent Dasypus novemcinctus and Tolypeutes matacus, respectively. Sloth 1 and 2 represent Choloepus hoffmanni and Choloepus didactylus, respectively.

Mentions: Mouse Sirh11/Zcchc16 encodes a Gag-like protein comprising 304 amino acids with a typical CCHC RNA-binding motif at the C-terminus (Fig 1A). It exhibits 37.5% homology with the entire sushi-ichi retrotransposon Gag, consisting of 371 amino acids, except for the N-terminus. Sirh11/Zcchc16 is located on the X chromosome between Trpc5 and Lhfpl1. Its location is conserved in all of the eutherian lineages, euarchontoglires, laurasiatheria, afrotheria and xenarthra (Fig 1B and 1C). However, it became a pseudogene by frameshift and nonsense mutation in xenarthran species, such as the armadillo and sloth (S1 Fig). In the case of the armadillo (Dasypus novemcinctus), contig including pseudoSIRH11/ZCCHC16 is short and thus does not reach LHFPL1 or TRPC5. However, the presence of several evolutionarily conserved sequences (ECSs) in its surrounding 20 kb sequence confirms that it is orthologous to SIRH11/ZCCHC16 (Fig 1B, lower column). The absence of SIRH11/ZCCHC16 from marsupials, monotremes and birds was also confirmed, because there is no orthologous gene between TRPC5 and LHFPL1 in the opossum and Tasmanian devil, or between TRPC5 and AMOT in the chicken and platypus, respectively (Fig 1B and 1C). This indicates that the insertion of SIRH11/ZCCHC16 occurred in a common eutherian ancestor after the spilt of the eutherians and marsupials 160 million years ago (Ma), before the diversification of the three major eutherian lineages, boreoeutheria (including euarchontoglires and laurasiatheria), afrotheria and xenarthra, 120 Ma [30].


Cognitive Function Related to the Sirh11/Zcchc16 Gene Acquired from an LTR Retrotransposon in Eutherians.

Irie M, Yoshikawa M, Ono R, Iwafune H, Furuse T, Yamada I, Wakana S, Yamashita Y, Abe T, Ishino F, Kaneko-Ishino T - PLoS Genet. (2015)

Characteristics of Sirh11/Zcchc16.(A) Structure of the Sirh11/Zcchc16 protein. The scheme shows the alignment of the sushi-ichi gag domain and Sirh11/Zcchc16 proteins, which overall exhibit 21% identity and 37.5% similarity, respectively. The zinc finger CCHC domain (purple) in the C-terminus is conserved, but the coiled-coil motif (green) and gag domain (blue) are absent in the Sirh11/Zcchc16 protein. (B) Chromosomal Location. SIRH11/ZCCH16 is conserved in an orthologous chromosomal region between TRPC5 and LHFPL1 in eutherian mammals. The upper panel shows that SIRH11/ZCCHC16 is absent in the chicken (birds), platypus (monotremes) and opossum (marsupials). The identically colored boxes represent orthologous genes and the light blue boxes represent psuedoSIRH11/ZCCHC16 genes. The lower panel provides a comparison of SIRH11/ZCCHC16 and its flanking genome sequences with 50~100% homology to the mouse genome in several eutherian mammals. The purple (SIRH11/ZCCHC16) and red (others) areas indicate evolutionarily conserved sequences (ECSs). The shaded area indicates the regions that correspond to the mouse Sirh11/Zcchc16 open reading frame. The yellow line in the Armadillo column represents the gap region in the genome sequence. (C) Conservation of Sirh11/Zcchc16 in eutherian mammals. The SIRH11/ZCCHC16 sequence was confirmed in four major eutherian groups (red), euarchontoglires, laurasiatheria, xenarthra and afrotheria, but became a pseudogene in xenarthra (the dashed line), indicating that the insertion of SIRH11/ZCCHC16 occurred in a common eutherian ancestor. The number of species possessing SIRH11/ZCCHC16 (front) and those which in total were analyzed (back) are noted in parentheses. (D) PAML analysis. Two models, the one-ratio model based on the assumption that ω1 (dN/dS) is the same for all of the branches (model 1) and the two-ratio model based on the assumption that ω2 in the xenathran lineage is different from ω1 in all the others (model 2) were compared. The model 2 was statistically significant and is shown. The p-value was calculated by the likelihood ratio test. Armadillo 1 and 2 represent Dasypus novemcinctus and Tolypeutes matacus, respectively. Sloth 1 and 2 represent Choloepus hoffmanni and Choloepus didactylus, respectively.
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Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581854&req=5

pgen.1005521.g001: Characteristics of Sirh11/Zcchc16.(A) Structure of the Sirh11/Zcchc16 protein. The scheme shows the alignment of the sushi-ichi gag domain and Sirh11/Zcchc16 proteins, which overall exhibit 21% identity and 37.5% similarity, respectively. The zinc finger CCHC domain (purple) in the C-terminus is conserved, but the coiled-coil motif (green) and gag domain (blue) are absent in the Sirh11/Zcchc16 protein. (B) Chromosomal Location. SIRH11/ZCCH16 is conserved in an orthologous chromosomal region between TRPC5 and LHFPL1 in eutherian mammals. The upper panel shows that SIRH11/ZCCHC16 is absent in the chicken (birds), platypus (monotremes) and opossum (marsupials). The identically colored boxes represent orthologous genes and the light blue boxes represent psuedoSIRH11/ZCCHC16 genes. The lower panel provides a comparison of SIRH11/ZCCHC16 and its flanking genome sequences with 50~100% homology to the mouse genome in several eutherian mammals. The purple (SIRH11/ZCCHC16) and red (others) areas indicate evolutionarily conserved sequences (ECSs). The shaded area indicates the regions that correspond to the mouse Sirh11/Zcchc16 open reading frame. The yellow line in the Armadillo column represents the gap region in the genome sequence. (C) Conservation of Sirh11/Zcchc16 in eutherian mammals. The SIRH11/ZCCHC16 sequence was confirmed in four major eutherian groups (red), euarchontoglires, laurasiatheria, xenarthra and afrotheria, but became a pseudogene in xenarthra (the dashed line), indicating that the insertion of SIRH11/ZCCHC16 occurred in a common eutherian ancestor. The number of species possessing SIRH11/ZCCHC16 (front) and those which in total were analyzed (back) are noted in parentheses. (D) PAML analysis. Two models, the one-ratio model based on the assumption that ω1 (dN/dS) is the same for all of the branches (model 1) and the two-ratio model based on the assumption that ω2 in the xenathran lineage is different from ω1 in all the others (model 2) were compared. The model 2 was statistically significant and is shown. The p-value was calculated by the likelihood ratio test. Armadillo 1 and 2 represent Dasypus novemcinctus and Tolypeutes matacus, respectively. Sloth 1 and 2 represent Choloepus hoffmanni and Choloepus didactylus, respectively.
Mentions: Mouse Sirh11/Zcchc16 encodes a Gag-like protein comprising 304 amino acids with a typical CCHC RNA-binding motif at the C-terminus (Fig 1A). It exhibits 37.5% homology with the entire sushi-ichi retrotransposon Gag, consisting of 371 amino acids, except for the N-terminus. Sirh11/Zcchc16 is located on the X chromosome between Trpc5 and Lhfpl1. Its location is conserved in all of the eutherian lineages, euarchontoglires, laurasiatheria, afrotheria and xenarthra (Fig 1B and 1C). However, it became a pseudogene by frameshift and nonsense mutation in xenarthran species, such as the armadillo and sloth (S1 Fig). In the case of the armadillo (Dasypus novemcinctus), contig including pseudoSIRH11/ZCCHC16 is short and thus does not reach LHFPL1 or TRPC5. However, the presence of several evolutionarily conserved sequences (ECSs) in its surrounding 20 kb sequence confirms that it is orthologous to SIRH11/ZCCHC16 (Fig 1B, lower column). The absence of SIRH11/ZCCHC16 from marsupials, monotremes and birds was also confirmed, because there is no orthologous gene between TRPC5 and LHFPL1 in the opossum and Tasmanian devil, or between TRPC5 and AMOT in the chicken and platypus, respectively (Fig 1B and 1C). This indicates that the insertion of SIRH11/ZCCHC16 occurred in a common eutherian ancestor after the spilt of the eutherians and marsupials 160 million years ago (Ma), before the diversification of the three major eutherian lineages, boreoeutheria (including euarchontoglires and laurasiatheria), afrotheria and xenarthra, 120 Ma [30].

Bottom Line: Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein.Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA) was reduced compared with dopamine (DA) after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO) mice.Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1.

View Article: PubMed Central - PubMed

Affiliation: School of Health Sciences, Tokai University, Isehara, Kanagawa, Japan; Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan.

ABSTRACT
Gene targeting of mouse Sushi-ichi-related retrotransposon homologue 11/Zinc finger CCHC domain-containing 16 (Sirh11/Zcchc16) causes abnormal behaviors related to cognition, including attention, impulsivity and working memory. Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein. Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA) was reduced compared with dopamine (DA) after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO) mice. These data indicate that Sirh11/Zcchc16 is involved in cognitive function in the brain, possibly via the noradrenergic system, in the contemporary mouse developmental systems. Interestingly, it is highly conserved in three out of the four major groups of the eutherians, euarchontoglires, laurasiatheria and afrotheria, but is heavily mutated in xenarthran species such as the sloth and armadillo, suggesting that it has contributed to brain evolution in the three major eutherian lineages, including humans and mice. Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1.

No MeSH data available.


Related in: MedlinePlus