I. Z. Plyusnina

Social Cognitive Evolution in Captive Foxes Is a Correlated By-Product of Experimental Domestication

Dogs have an unusual ability for reading human communicative gestures (e.g., pointing) in comparison to either nonhuman primates (including chimpanzees) or wolves . Although this unusual communicative ability seems to have evolved during domestication , it is unclear whether this evolution occurred as a result of direct selection for this ability, as previously hypothesized , or as a correlated by-product of selection against fear and aggression toward humans--as is the case with a number of morphological and physiological changes associated with domestication . We show here that fox kits from an experimental population selectively bred over 45 years to approach humans fearlessly and nonaggressively (i.e., experimentally domesticated) are not only as skillful as dog puppies in using human gestures but are also more skilled than fox kits from a second, control population not bred for tame behavior (critically, neither population of foxes was ever bred or tested for their ability to use human gestures) . These results suggest that sociocognitive evolution has occurred in the experimental foxes, and possibly domestic dogs, as a correlated by-product of selection on systems mediating fear and aggression, and it is likely the observed social cognitive evolution did not require direct selection for improved social cognitive ability.

An Experiment on Fox Domestication and Debatable Issues of Evolution of the Dog

This paper is a review of the results of the authors obtained in a long-term experiment on fox domestication. Debatable issues of dog evolution are discussed in light of these results. It is demonstrated that genetic physiological mechanisms of the behavior transformation during selection and the nature of the arising phenotypic changes are associated with retarded development of corresponding ontogenetic processes. As a result of this retardation, the adult animals retain juvenile traits of behavior and morphology (the phenomenon of neoteny). The role of hormonal changes caused by domestication in the evolutionary origin of neoteny is discussed.

Phenotypic differences in behavior, physiology and neurochemistry between rats selected for tameness and for defensive aggression towards humans

To better understand the biology of tameness, i.e. tolerance of human presence and handling, we analyzed two lines of wild-derived rats (Rattus norvegicus) artificially selected for tameness and defensive aggression towards humans. In response to a gloved human hand, tame rats tolerated handling, whereas aggressive rats attacked. Cross-fostering showed that these behavioral differences are not caused by postnatal maternal effects. Tame rats were more active and explorative and exhibited fewer anxiety-related behaviors. They also had smaller adrenal glands, larger spleens and lower levels of serum corticosterone. Blood glucose levels were lower in tame rats, whereas the concentrations of nine amino acids were higher. In the brain, tame rats had lower serotonin and higher taurine levels than aggressive rats. Our findings reinforce the notion that tameness is correlated with differences in stress response and will facilitate future efforts to uncover the genetic basis for animal tameness.

Genetic Architecture of Tameness in a Rat Model of Animal Domestication

A common feature of domestic animals is tameness—i.e., they tolerate and are unafraid of human presence and handling. To gain insight into the genetic basis of tameness and aggression, we studied an intercross between two lines of rats (Rattus norvegicus) selected over >60 generations for increased tameness and increased aggression against humans, respectively. We measured 45 traits, including tameness and aggression, anxiety-related traits, organ weights, and levels of serum components in >700 rats from an intercross population. Using 201 genetic markers, we identified two significant quantitative trait loci (QTL) for tameness. These loci overlap with QTL for adrenal gland weight and for anxiety-related traits and are part of a five-locus epistatic network influencing tameness. An additional QTL influences the occurrence of white coat spots, but shows no significant effect on tameness. The loci described here are important starting points for finding the genes that cause tameness in these rats and potentially in domestic animals in general.

A Comparison of Brain Gene Expression Levels in Domesticated and Wild Animals

Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits). We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea) as well as between two lines of rats selected for tameness or aggression towards humans. There were few gene expression differences between domesticated and wild dogs, pigs, and rabbits (30–75 genes (less than 1%) of expressed genes were differentially expressed), while guinea pigs and C. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in the different domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestive evidence for the existence of a small group of genes that changed their expression in a similar fashion in different domesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6 and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticated animals and the tame and aggressive rats. However, two of the genes with the strongest expression differences between the rats (DLL3 and DHDH) were located in a genomic region associated with tameness and aggression, suggesting a role in influencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific to the given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise be different.

Specific [3H]8-OH-DPAT binding in brain regions of rats genetically predisposed to various defense behavior strategies

Distribution of 5-HT1A receptors was studied in rats genetically predisposed to two basic defense strategies--passive (freezing) or active (aggression) defensive behavior. Specific [3H]8-OH-DPAT binding was assayed in the brain structures of rat strains bred for 40 generations from Wistar stock for predisposition to freezing (catalepsy), and in wild rats bred for low and high aggression to humans. Considerable changes in [3H]8-OH-DPAT binding were found in the brain of rats with hereditary predisposition to catalepsy. A significant decrease in Bmax of specific receptor binding of [3H]8-OH-DPAT in the frontal cortex, and in the striatum as well as an increase in Kd in the hippocampus of cataleptic rats was shown. A clear-cut tendency to decrease of 5-HT1A receptor density was observed in the midbrain and hypothalamus of these rats. A comparison of wild Norway rats bred for aggressiveness against humans with those bred for the absence of affective aggressiveness showed a Bmax decrease without Kd change in the frontal cortex, hypothalamus, and amygdala of aggressive animals. It is hypothesized that 5-HT1A and probably 5-HT1A-like 5-HT7 serotonin receptors are involved in the mechanisms of both active and passive defense reactions, and the high expression of fear-induced defense is associated with their decrease in the frontal cortex. At the same time, the genetically determined preference for a certain defense behavior strategy depends either on the peculiarities of distribution of these receptor types in the brain regions or on some other types of serotonin receptors.

Effect of Domestication on Aggression in Gray Norway Rats

A comparative analysis of intermale aggression in the resident–intruder test was conducted with gray rats from a wild unselected population bred at the laboratory for three generations and gray rats selected for elimination (tame) and enhancement (aggressive) of aggressiveness towards human for 71–72 generations. Males from the laboratory line Wistar were used as neutral opponents. Rats from the tame line were characterized by reduced aggression manifest as longer attack latency, decreased number of attacks, upright postures, chases, kicks, and shorter total time of aggressive behavior compared to unselected males. There was no significant difference in the attack latency and the total time of aggression between rats of the aggressive line and unselected rats. A trend to decrease in the number of attacks, chases and upright postures and to increase in contribution of lateral threat postures to the total time of aggression was observed for males of the aggressive line. Plasma corticosterone in unselected males not presented with intruders and after their presentation was higher than in males of both selected lines. Comparative behavioral analysis of agonistic behaviors in rats from the aggressive and tame lines to opponents of different lines (Wistar, tame, aggressive) showed that the presence of an intruder from the aggressive line can enhance aggressive responses in residents from the tame line. Thus, selection for domestication of gray rats caused a significant attenuation of aggressive behavior without affecting the basic agonistic repertoire.

Cross-fostering Effects on Weight, Exploratory Activity, Acoustic Startle Reflex and Corticosterone Stress Response in Norway Gray Rats Selected for Elimination and for Enhancement of Aggressiveness Towards Human

Two rat lines, one tame, the other aggressive, differing by many behavioral features and stress reactivity were developed by long-term selection of wild gray rats for elimination and enhancement of aggressiveness towards humans. The aim of this work was to study the role of the maternal environment in the expression of these differences between the two rat lines using the cross-fostering paradigm. Fostering of tame rats of both sexes by aggressive mothers and aggressive females by tame mothers was without effect on behavior score towards humans, but the cross-fostered aggressive males had a small, yet significant, increase in aggressiveness score. Cross-fostering revealed that exploratory behavior in the hole-board test and the acoustic startle amplitude were weakly affected by maternal interactions, although there was an effect on body weight and on the stress corticosterone response. Body weight was decreased in tame males fostered by aggressive mothers only and it was increased in cross-fostered aggressive rats of both sexes. Fostering of tame males and females by an aggressive mother enhanced almost twofold the corticosterone response immediately after stress, while fostering of aggressive ratlings of both sexes by a tame mother was without effect. The current results demonstrated that the maternal postnatal environment had no substantial effect on the behavioral responses of both tame and aggressive rats, but it possibly contributed to the development of the corticosterone response to restraint stress in the tame, and not the aggressive rats, i.e. these effects of cross-fostering were dependent on ratling genotype.

Genetic influences on brain gene expression in rats selected for tameness and aggression

Interindividual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior toward humans for >64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40, and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals.

Functional Characteristics of Serotonin 5-HT2A and 5-HT2C Receptors in the Brain and the Expression of the 5-HT2A and 5-HT2C Receptor Genes in Aggressive and Non-Aggressive Rats

The functional activity of serotonin 5-HT2A and 5-HT2C receptors and the expression of the genes encoding them were studied in Norway rats bred for 60 generations for the presence and absence of high levels of stress-evoked aggression to humans. There were no significant differences in the levels of 5-HT2A receptor mRNA in the midbrain, frontal cortex, and hippocampus and the extents of head twitching evoked by the 5-HT2A agonist DOI in rats with and without genetically determined high levels of aggression. Administration of the selective 5-HT2C agonist MK-212 weakened reflex startle in response to an acoustic signal (the acoustic startle response) in non-aggressive animals but had no significant effects on the response in aggressive animals. Increases in the level of 5-HT2C receptor mRNA were seen in the frontal cortex and hippocampus in non-aggressive rats as compared with aggressive animals. Increases in the expression of the 5-HT2C receptor gene and the functional state of 5-HT2C receptors were seen in the brains of non-aggressive rats, without any changes in the 5-HT2A receptor mRNA level or receptor sensitivity; this is evidence for the involvement of 5-HT2C receptors in the mechanisms inhibiting fear-evoked aggressive behavior.