Behavioral variation in human beings encompasses wide differences in personality and susceptibility to psychiatric illness arising from both genotype and experience. Long-lasting behavioral differences generally have heritabilities of 30% or more, and such inheritance is ultimately attributable to functional variants of genes programming brain development and function. The sequencing of the human genome is revealing a pattern of gene sequence variation. The ability of sequence variants to affect neural function either alone or in concert may reveal effects of behavioral selection on the human genome over evolutionary time frames. Dopamine and serotonin are phylogenetically ancient neurotransmitters intrinsic to brain function and behavior. Dopamine and serotonin receptor and transporter genes have been an early focus for efforts to identify and functionally characterize sequence variation. The purpose of this article is to present a preview of a developing new perspective in human behavior: the genetic variation of the brain or neurochemical individuality.
Phylogenetic trees for human dopamine (D) and serotonin (5-HT) G protein–coupled receptors. A, Phenogram representing genetic distances. This analysis supports the suggestion that dopamine, 5-HT1, 5-HT5, 5-HT7, and 5-HT4 receptors evolved from a common ancestor after the initial divergence of the 5-HT2 and 5-HT6 receptor subtypes.11 B, Most parsimonious tree. The 3 major divisions in the evolutionary topology correspond to a signal transduction mechanism rather than ligand specificity: coupling to Gq proteins (leading to increased phosphoinositol), Gs proteins (increased cyclic adenosine monophosphate [cAMP]) and Gi proteins (decreased cAMP). The 5-HT5A–signalling mechanism remains unclear, and this is convergent with its position in the evolutionary topology based on sequence. PI indicates phosphoinositol; AC, cAMP; ↑, increase; and ↓, decrease.
Putative membrane topography of a consensus protein sequence for all the human dopamine (D) and serotonin (5-HT) G protein–coupled receptors. Functionally conserved residues are color coded. Receptor protein variants are also depicted in different colors according to allele frequency. NH2 indicates the amino group; COOH, carboxyl group; bp del, base pair deletion; aa, amino acid; A, alanine; R, arginine; N, asparagine; D, aspartic acid; C, cysteine; E, glutamic acid; G, glycine; I, isoleucine; L, leucine; K, lysine; M, methionine; F, phenylalanine; P, proline; S, serine; T, threonine; W, tryptophan; Y, tyrosine; and V, valine.
Thank you for submitting a comment on this article. It will be reviewed by JAMA Psychiatry editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 62
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.