A Pathway-Centered Analysis of Pig Domestication and Breeding in Eurasia

Abstract

Ascertaining the molecular and physiological basis of domestication and breeding is an active area of research. Due to the current wide distribution of its wild ancestor, the wild boar, the pig (Sus scrofa) is an excellent model to study these processes, which occurred independently in East Asia and Europe ca. 9000 yr ago. Analyzing genome variability patterns in terms of metabolic pathways is attractive since it considers the impact of interrelated functions of genes, in contrast to genome-wide scans that treat genes or genome windows in isolation. To that end, we studied 40 wild boars and 123 domestic pig genomes from Asia and Europe when metabolic pathway was the unit of analysis. We computed statistical significance for differentiation (Fst) and linkage disequilibrium (nSL) statistics at the pathway level. In terms of Fst, we found 21 and 12 pathways significantly differentiated at a q-value < 0.05 in Asia and Europe, respectively; five were shared across continents. In Asia, we found six significant pathways related to behavior, which involved essential neurotransmitters like dopamine and serotonin. Several significant pathways were interrelated and shared a variable percentage of genes. There were 12 genes present in >10 significant pathways (in terms of Fst), comprising genes involved in the transduction of a large number of signals, like phospholipase PCLB1, which is expressed in the brain, or ITPR3, which has an important role in taste transduction. In terms of nSL, significant pathways were mainly related to reproductive performance (ovarian steroidogenesis), a similarly important target trait during domestication and modern animal breeding. Different levels of recombination cannot explain these results, since we found no correlation between Fst and recombination rate. However, we did find an increased ratio of deleterious mutations in domestic vs. wild populations, suggesting a relaxed functional constraint associated with the domestication and breeding processes. Purifying selection was, nevertheless, stronger in significantly differentiated pathways than in random pathways, mainly in Europe. We conclude that pathway analysis facilitates the biological interpretation of genome-wide studies. Notably, in the case of pig, behavior played an important role, among other physiological and developmental processes.

Analysis of Gene Expression Variance in Schizophrenia Using Structural Equation Modeling

“…We ranked the list of genes according to the estimated p -values, and applied the fast gene set enrichment analysis (FGSEA) method (available as the Bioconductor package “fgsea”; Sergushichev, 2016), for each pathway. We also conducted another Gene Set Analysis (GSA)–node-based enrichment analysis which aggregates p -values of Levene’s test by Fisher’s method (Leno-Colorado et al, 2017). …”

Converging roles of glutamate receptors in domestication and prosociality

“…In studies of genetic differences between tame and aggressive foxes, changes to serotonergic signaling accompany those of the glutamatergic system, with genetic changes often po-tentially relevant to both synapses [30,31]. Similarly, domestication of the pig appears to have involved important changes across both systems [36]. Signals of selection associated with serotonergic signaling have also been identified in a tame strain of rat and the domesticated goat [105,106].…”

“…In several of the studies cited in Table 2, signals of selection on glutamate receptor genes have been suggested as potentially important for behavioral changes during the domestication process [23,27,28,29,30,36,41]. However, such suggestions form part of broader discussion on changes to genes related to the central nervous system (CNS) under domestication, and no mechanistic details are provided.…”

RAPID COMMUNICATION: A haplotype information theory method reveals genes of evolutionary interest in European vs. Asian pigs1

“…We analyzed complete genome sequence from 46 domestic and wild pigs from Asia and Europe (Leno-Colorado et al, 2017;Pérez-Enciso et al, 2017). In brief, the sampling scheme was designed to be as balanced as possible while simultaneously aiming at capturing variability within continents and within domestic status.…”

“…Here, we used 23 individuals in each of the two phylogeographic groups. The use of a previously published (Leno-Colorado et al, 2017;Perez-Enciso et al, 2017) de novo SNP identification approach from genome sequencing gave us a very high resolution analytical tool with which to scrutinize the population history and genetics of these animals.…”