TY - JOUR
T1 - Serotonin receptor 1a variation is associated with anxiety and agonistic behavior in chimpanzees
AU - Staes, Nicky
AU - Sherwood, Chet C.
AU - Freeman, Hani
AU - Brosnan, Sarah F.
AU - Schapiro, Steven J.
AU - Hopkins, William D.
AU - Bradley, Brenda J.
N1 - Funding Information:
We thank colleagues for help with providing DNA samples, specifically: the Yerkes National Primate Research Center, The Michale E. Keeling Center for Comparative Medicine and Research, and John J. Ely. We thank Andrew Barr for his statistical advice, and Arash Panjwani for help with data compilation. We also thank all members of the Primate Genomics Lab and the Laboratory for Evolutionary Neuroscience at the George Washington University for helpful feedback on the project. This work was supported by the National Science Foundation (SMA 1542848 to N.S., C.C.S., W.D.H., S.J.S., and B.J.B., and SES 1425216 to S.F.B.), and the James S. McDonnell Foundation (220020293 to C.C.S.). The collection of the behavioral data was funded by a grant from the MacArthur Foundation Preferences Network to Joan B. Silk, Joseph Henrich, and Daniel Povinelli. The authors declare that there are no conflicts of interest to report.
Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Serotonin is a neurotransmitter that plays an important role in regulating behavior and personality in humans and other mammals. Polymorphisms in genes coding for the serotonin receptor subtype 1A (HTR1A), the serotonin transporter (SLC6A4), and the serotonin degrading enzyme monoamine oxidase A (MAOA) are associated with anxiety, impulsivity, and neurotic personality in humans. In primates, previous research has largely focused on SLC6A4 and MAOA, with few studies investigating the role of HTR1A polymorphic variation on behavior. Here, we examined variation in the coding region of HTR1A across apes, and genotyped polymorphic coding variation in a sample of 214 chimpanzees with matched measures of personality and behavior. We found evidence for positive selection at three amino acid substitution sites, one in chimpanzees-bonobos (Thr26Ser), one in humans (Phe33Val), and one in orangutans (Ala274Gly). Investigation of the HTR1A coding region in chimpanzees revealed a polymorphic site, where a C/A single nucleotide polymorphism changes a proline to a glutamine in the amino acid sequence (Pro248Gln). The substitution is located in the third intracellular loop of the receptor, a region important for serotonin signal transduction. The derived variant is the major allele in this population (frequency 0.67), and is associated with a reduction in anxiety, decreased rates of male agonistic behavior, and an increase in socio-positive behavior. These results are the first evidence that the HTR1A gene may be involved in regulating social behavior in chimpanzees and encourage further systematic investigation of polymorphic variation in other primate populations with corresponding data on behavior.
AB - Serotonin is a neurotransmitter that plays an important role in regulating behavior and personality in humans and other mammals. Polymorphisms in genes coding for the serotonin receptor subtype 1A (HTR1A), the serotonin transporter (SLC6A4), and the serotonin degrading enzyme monoamine oxidase A (MAOA) are associated with anxiety, impulsivity, and neurotic personality in humans. In primates, previous research has largely focused on SLC6A4 and MAOA, with few studies investigating the role of HTR1A polymorphic variation on behavior. Here, we examined variation in the coding region of HTR1A across apes, and genotyped polymorphic coding variation in a sample of 214 chimpanzees with matched measures of personality and behavior. We found evidence for positive selection at three amino acid substitution sites, one in chimpanzees-bonobos (Thr26Ser), one in humans (Phe33Val), and one in orangutans (Ala274Gly). Investigation of the HTR1A coding region in chimpanzees revealed a polymorphic site, where a C/A single nucleotide polymorphism changes a proline to a glutamine in the amino acid sequence (Pro248Gln). The substitution is located in the third intracellular loop of the receptor, a region important for serotonin signal transduction. The derived variant is the major allele in this population (frequency 0.67), and is associated with a reduction in anxiety, decreased rates of male agonistic behavior, and an increase in socio-positive behavior. These results are the first evidence that the HTR1A gene may be involved in regulating social behavior in chimpanzees and encourage further systematic investigation of polymorphic variation in other primate populations with corresponding data on behavior.
KW - Behavioral genetics
KW - Behavioral tendencies
KW - Display
KW - Personality
KW - Primates
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U2 - 10.1093/molbev/msz061
DO - 10.1093/molbev/msz061
M3 - Article
C2 - 31045220
AN - SCOPUS:85068243792
SN - 0737-4038
VL - 36
SP - 1418
EP - 1429
JO - Molecular biology and evolution
JF - Molecular biology and evolution
IS - 7
ER -