From species differences to individual differences.

摘要: In his seminal work, The Origin of Species, Darwin begins with a long discourse on variation in domesticated species.1 He considers the differences strains pigeons, sheep, and dogs to address fundamental questions how when new species form. suggests that are result extreme within-species variation. Individual changes become so buds off from an existing one either physical isolation or environmental pressure. Although could not know about modern genetics, contemporary terms hypothesis be re-stated as precedes between-species Comparative genomics flips this by proposing regions vary between likely hotspots individuals. Over past decade, series comparative papers Larry Young co-workers have demonstrated extraordinary sequence vasopressin V1a receptor gene (AVPR1a).2 This subtype is expressed brain, especially hypothalamus, lateral septum, amygdala, and, some species, ventral striatum. Activation increases social interaction, but there striking behavioral response activation anatomic location receptor. As general rule, pattern expression correlates organization. Specifically, monogamous mammals, rodents primates, abundant receptors striatum non-monogamous few areas associated reward.3 Most important, appears determined length microsatellite promoter region AVPR1a.4 Readers journal familiar serotonin transporter its role for altering amount protein. AVPR1a similar, influence only protein, where brain protein expressed. model then leads anatomical resulting behavior following endogenous release. recently, Hammock application comparison chimpanzees bonobos, two closely related great apes markedly different behavior.4 Could difference sequence, chemistry, relevant individual within human species? humans, found chromosome 12q14–15, observed at three microsatellites (RS1 RS3 intronic allele identified AVR). paper Yirmiya et al. issue Molecular Psychiatry third report test association variations these autism, which fundamentally deficit behavior.5, 6, 7 Kim al.5 17 alleles RS1, showed increased transmission family-based study 115 autism trios. Wassink al.6 significant disequilibrium both RS1 cases without language deficits. paper, al.7 fail find microsatellite. They note moderate linkage microsatellites. most ADOS-G, composite measure deficits (especially skills) haplotypes. Taken together, suggest link possibly confirming value identifying hot spots genome. Now challenge will move genetics biology, has been done already studies vole Are any functional? Can particular haplotype drive patterns brain? Do patients show altered Given evidence linking oxytocin behavior, we need comprehensive maps genotypes, measures brains autistic patients. If, suggested genomic responsible stunning confirmation idea 150 years ago: mechanisms speciation can also Understanding lead inexorably understanding including those adverse define disease states.