Selection for tameness modulates the expression of heme related genes in silver foxes

Abstract

Background: The genetic and molecular mechanisms of tameness are largely unknown. A line of silver foxes (Vulpes vulpes) selected for non-aggressive behavior has been used in Russia since the 1960's to study the effect of domestication. We have previously compared descendants of these selected (S) animals with a group of non-selected (NS) silver foxes kept under identical conditions, and showed that changes in the brain transcriptome between the two groups are small. Unexpectedly, many of the genes showing evidence of differential expression between groups were related to hemoproteins.

Results: In this study, we use quantitative RT-PCR to demonstrate that the activity of heme related genes differ between S and NS foxes in three regions of the brain. Furthermore, our analyses also indicate that changes in mRNA levels of heme related genes can be well described by an additive polygenic effect. We also show that the difference in genetic background between the two lines of foxes is limited, as estimated by mitochondrial DNA divergence.

Conclusion: Our results indicate that selection for tameness can modify the expression of heme related genes in canid brain regions known to modulate emotions and behavior. The possible involvement of heme related genes in behavior is surprising. It is possible that hemoglobin modulates the behavior of canids by interaction with CO and NO signaling. Another possibility is that hemorphins, known to be produced after enzymatic cleavage of hemoglobin, are responsible for behavioral alterations. Thus, we hypothesize that hemoglobin metabolism can be a functionally relevant aspect of the domestic phenotype in foxes selected for tameness.

Figure 1

Neighbor-joining phylogenetic tree based on mtDNA control region. Sequences corresponding to the non-selected (NS) foxes (□), selected (S) foxes (■) and wild foxes from one population (*). Sequences of other wild foxes obtained from GenBank are indicated by a dot. Bootstrap support is indicated when higher than 50%.

Figure 2

Gene expression levels of heme related genes in fox brain. Average mRNA levels of hemoglobin alpha (HBA), beta (HBB) and epsilon (HBE) chains, and heme binding protein (HEBP1) are shown for four groups of foxes, Vulpes vulpes. Wild = wild red foxes (N = 12), NS = non selected farm foxes (N = 17), S = farm foxes selected for tame behavior (N = 9), Cross = off-spring from crosses and back crosses of NS and S foxes (N = 12). Least square means and standard errors are given.