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Genome analysis reveals insights into physiology and longevity of the Brandt's bat Myotis brandtii.

Seim I, Fang X, Xiong Z, Lobanov AV, Huang Z, Ma S, Feng Y, Turanov AA, Zhu Y, Lenz TL, Gerashchenko MV, Fan D, Hee Yim S, Yao X, Jordan D, Xiong Y, Ma Y, Lyapunov AN, Chen G, Kulakova OI, Sun Y, Lee SG, Bronson RT, Moskalev AA, Sunyaev SR, Zhang G, Krogh A, Wang J, Gladyshev VN - Nat Commun (2013)

Bottom Line: Bats account for one-fifth of mammalian species, are the only mammals with powered flight, and are among the few animals that echolocate.The insect-eating Brandt's bat (Myotis brandtii) is the longest-lived bat species known to date (lifespan exceeds 40 years) and, at 4-8 g adult body weight, is the most extreme mammal with regard to disparity between body mass and longevity.Here we report sequencing and analysis of the Brandt's bat genome and transcriptome, which suggest adaptations consistent with echolocation and hibernation, as well as altered metabolism, reproduction and visual function.

View Article: PubMed Central - PubMed

Affiliation: 1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, South Korea [3].

ABSTRACT
Bats account for one-fifth of mammalian species, are the only mammals with powered flight, and are among the few animals that echolocate. The insect-eating Brandt's bat (Myotis brandtii) is the longest-lived bat species known to date (lifespan exceeds 40 years) and, at 4-8 g adult body weight, is the most extreme mammal with regard to disparity between body mass and longevity. Here we report sequencing and analysis of the Brandt's bat genome and transcriptome, which suggest adaptations consistent with echolocation and hibernation, as well as altered metabolism, reproduction and visual function. Unique sequence changes in growth hormone and insulin-like growth factor 1 receptors are also observed. The data suggest that an altered growth hormone/insulin-like growth factor 1 axis, which may be common to other long-lived bat species, together with adaptations such as hibernation and low reproductive rate, contribute to the exceptional lifespan of the Brandt's bat.

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FSHβ of the Brandt’s bat harbours a radical amino-acid substitution in a conserved position.(a) Alignment of FSHB-encoded peptide sequences. Amino-acid numbering corresponds to the mature FSHβ peptide. (b) Structural model of FSHβ (cyan), the follicle-stimulating hormone receptor FSHR (grey) and the glycoprotein hormones α chain GLHA/FSHα (green) (PDB ID code 1xwd). In both subfigures, FSHβ residues buried at the FSHR receptor–ligand interface are highlighted in purple, while a radical amino-acid substitution within the interface in bats with delayed ovulation is shown in red.
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f3: FSHβ of the Brandt’s bat harbours a radical amino-acid substitution in a conserved position.(a) Alignment of FSHB-encoded peptide sequences. Amino-acid numbering corresponds to the mature FSHβ peptide. (b) Structural model of FSHβ (cyan), the follicle-stimulating hormone receptor FSHR (grey) and the glycoprotein hormones α chain GLHA/FSHα (green) (PDB ID code 1xwd). In both subfigures, FSHβ residues buried at the FSHR receptor–ligand interface are highlighted in purple, while a radical amino-acid substitution within the interface in bats with delayed ovulation is shown in red.

Mentions: In Myotis, mating occurs right before or during hibernation, where males can mate with torpid females. The sperm is then stored in the female reproductive tract, with ovulation and fertilization delayed until spring30. Follicle-stimulating hormone (FSH) is a glycoprotein hormone consisting of a common α-subunit and a hormone-specific β-subunit. The hormone binds to its cognate G-protein-coupled receptor (FSH receptor; FSHR) in the testis and ovary and, together with luteinizing hormone (LH) and its receptor (LHR), is produced in the anterior pituitary and essential for reproduction. We found a unique amino-acid change (S89R) of potential functional significance in the mature FSH beta-subunit (FSHβ) peptide of hibernating bats (Fig. 3 and Supplementary Fig. S14). This change occurs within the hydrophobic receptor–ligand interface that determines receptor-binding specificity31, and the replacement of a small amino acid with a large, charged one would be expected to disrupt the FSHβ–FSHR interaction. Interestingly, it has recently been hypothesized31 that Ser89 may explain why LH cannot bind FSHR. LH, encoded by LHB, is a paralogous gene to FSHB and the LH beta-subunit (LHβ) is similar to FSHβ but harbours arginine at the site homologous to Ser89. Moreover, site-directed mutagenesis of residues 88–91 of FSHβ (DSDS) to the LHβ sequence (RRST) allows FSHβ to bind LHR32. A study of the Asiatic greater yellow house bat (Scotophilus heathi), which is in the same family as M. brandtii, suggests that increased responsiveness to LH could be associated with delayed ovulation33. Taken together, we hypothesize that an aberrant gonadotropin system, where FSH may have reduced affinity for FSHR and a gain-of-affinity for LHR, may contribute to the delayed ovulation observed in many bat species. Future studies using, for example, knock-in mice expressing a Ser89Arg mutation, should provide interesting insights into the phenotypic consequences of this amino-acid change.


Genome analysis reveals insights into physiology and longevity of the Brandt's bat Myotis brandtii.

Seim I, Fang X, Xiong Z, Lobanov AV, Huang Z, Ma S, Feng Y, Turanov AA, Zhu Y, Lenz TL, Gerashchenko MV, Fan D, Hee Yim S, Yao X, Jordan D, Xiong Y, Ma Y, Lyapunov AN, Chen G, Kulakova OI, Sun Y, Lee SG, Bronson RT, Moskalev AA, Sunyaev SR, Zhang G, Krogh A, Wang J, Gladyshev VN - Nat Commun (2013)

FSHβ of the Brandt’s bat harbours a radical amino-acid substitution in a conserved position.(a) Alignment of FSHB-encoded peptide sequences. Amino-acid numbering corresponds to the mature FSHβ peptide. (b) Structural model of FSHβ (cyan), the follicle-stimulating hormone receptor FSHR (grey) and the glycoprotein hormones α chain GLHA/FSHα (green) (PDB ID code 1xwd). In both subfigures, FSHβ residues buried at the FSHR receptor–ligand interface are highlighted in purple, while a radical amino-acid substitution within the interface in bats with delayed ovulation is shown in red.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3753542&req=5

f3: FSHβ of the Brandt’s bat harbours a radical amino-acid substitution in a conserved position.(a) Alignment of FSHB-encoded peptide sequences. Amino-acid numbering corresponds to the mature FSHβ peptide. (b) Structural model of FSHβ (cyan), the follicle-stimulating hormone receptor FSHR (grey) and the glycoprotein hormones α chain GLHA/FSHα (green) (PDB ID code 1xwd). In both subfigures, FSHβ residues buried at the FSHR receptor–ligand interface are highlighted in purple, while a radical amino-acid substitution within the interface in bats with delayed ovulation is shown in red.
Mentions: In Myotis, mating occurs right before or during hibernation, where males can mate with torpid females. The sperm is then stored in the female reproductive tract, with ovulation and fertilization delayed until spring30. Follicle-stimulating hormone (FSH) is a glycoprotein hormone consisting of a common α-subunit and a hormone-specific β-subunit. The hormone binds to its cognate G-protein-coupled receptor (FSH receptor; FSHR) in the testis and ovary and, together with luteinizing hormone (LH) and its receptor (LHR), is produced in the anterior pituitary and essential for reproduction. We found a unique amino-acid change (S89R) of potential functional significance in the mature FSH beta-subunit (FSHβ) peptide of hibernating bats (Fig. 3 and Supplementary Fig. S14). This change occurs within the hydrophobic receptor–ligand interface that determines receptor-binding specificity31, and the replacement of a small amino acid with a large, charged one would be expected to disrupt the FSHβ–FSHR interaction. Interestingly, it has recently been hypothesized31 that Ser89 may explain why LH cannot bind FSHR. LH, encoded by LHB, is a paralogous gene to FSHB and the LH beta-subunit (LHβ) is similar to FSHβ but harbours arginine at the site homologous to Ser89. Moreover, site-directed mutagenesis of residues 88–91 of FSHβ (DSDS) to the LHβ sequence (RRST) allows FSHβ to bind LHR32. A study of the Asiatic greater yellow house bat (Scotophilus heathi), which is in the same family as M. brandtii, suggests that increased responsiveness to LH could be associated with delayed ovulation33. Taken together, we hypothesize that an aberrant gonadotropin system, where FSH may have reduced affinity for FSHR and a gain-of-affinity for LHR, may contribute to the delayed ovulation observed in many bat species. Future studies using, for example, knock-in mice expressing a Ser89Arg mutation, should provide interesting insights into the phenotypic consequences of this amino-acid change.

Bottom Line: Bats account for one-fifth of mammalian species, are the only mammals with powered flight, and are among the few animals that echolocate.The insect-eating Brandt's bat (Myotis brandtii) is the longest-lived bat species known to date (lifespan exceeds 40 years) and, at 4-8 g adult body weight, is the most extreme mammal with regard to disparity between body mass and longevity.Here we report sequencing and analysis of the Brandt's bat genome and transcriptome, which suggest adaptations consistent with echolocation and hibernation, as well as altered metabolism, reproduction and visual function.

View Article: PubMed Central - PubMed

Affiliation: 1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, South Korea [3].

ABSTRACT
Bats account for one-fifth of mammalian species, are the only mammals with powered flight, and are among the few animals that echolocate. The insect-eating Brandt's bat (Myotis brandtii) is the longest-lived bat species known to date (lifespan exceeds 40 years) and, at 4-8 g adult body weight, is the most extreme mammal with regard to disparity between body mass and longevity. Here we report sequencing and analysis of the Brandt's bat genome and transcriptome, which suggest adaptations consistent with echolocation and hibernation, as well as altered metabolism, reproduction and visual function. Unique sequence changes in growth hormone and insulin-like growth factor 1 receptors are also observed. The data suggest that an altered growth hormone/insulin-like growth factor 1 axis, which may be common to other long-lived bat species, together with adaptations such as hibernation and low reproductive rate, contribute to the exceptional lifespan of the Brandt's bat.

Show MeSH
Related in: MedlinePlus