Epimutations in Developmental Genes Underlie the Onset of Domestication in Farmed European Sea Bass

Abstract

Domestication of wild animals induces a set of phenotypic characteristics collectively known as the domestication syndrome. However, how this syndrome emerges is still not clear. Recently, the neural crest cell deficit hypothesis proposed that it is generated by a mildly disrupted neural crest cell developmental program, but clear support is lacking due to the difficulties of distinguishing pure domestication effects from preexisting genetic differences between farmed and wild mammals and birds. Here, we use a farmed fish as model to investigate the role of persistent changes in DNA methylation (epimutations) in the process of domestication. We show that early domesticates of sea bass, with no genetic differences with wild counterparts, contain epimutations in tissues with different embryonic origins. About one fifth of epimutations that persist into adulthood are established by the time of gastrulation and affect genes involved in developmental processes that are expressed in embryonic structures, including the neural crest. Some of these genes are differentially expressed in sea bass with lower jaw malformations, a key feature of domestication syndrome. Interestingly, these epimutations significantly overlap with cytosine-to-thymine polymorphisms after 25 years of selective breeding. Furthermore, epimutated genes coincide with genes under positive selection in other domesticates. We argue that the initial stages of domestication include dynamic alterations in DNA methylation of developmental genes that affect the neural crest. Our results indicate a role for epimutations during the beginning of domestication that could be fixed as genetic variants and suggest a conserved molecular process to explain Darwin’s domestication syndrome across vertebrates.

Human Social Evolution: Self-Domestication or Self-Control?

“…A study of very recent domesticates of sea bass, which show no genetic differences from wild fish, found that these recent domesticates have epimutations (differences in patterns of DNA methylation) in various tissues, with about one fifth of the persistent epimutations being in genes that are expressed in embryonic structures, including the neural crest. Furthermore, the epimutated genes coincide with mutated genes in established domesticates (Anastasiadi and Piferrer, 2019). It is therefore plausible that a comparative study of epigenetic (e.g., methylation) differences among domesticates and humans will reveal many more substantial similarities and differences than gene-sequence differences, but at present there are only a few comparative studies that address this question.…”

Genome-Wide Epigenomic Stress Response in the European Sea Bass (Dicentrarchus Labrax, L.)

“…Main observations might be summarized as follows: all studies considering brain tissue for which gene annotations were made available (n = 6) reported at least one match with DMC-related genes found in the present study. More speci cally, data of the single former sea bass epigenetic study performed at a genome-wide level [83] reported ve genes of the present study as differentially methylated in the brain (GLG1a, GFRA2, CELF2, PRKCQ, ROBO3), three in muscle (CILP1, FURIN, KBTBD13), one in testis (GLG1a), and any in liver (total: eight distinct genes). This indicated slightly more matches with the brain than with other organs investigated so far.…”

“…Taking advantage of the epiGBS protocol that allow to process more samples [88], the number of individuals considered in this study is rather high (n = 70 distinct individuals), when most epigenomic studies in sh dealt with less than 30 individuals (range: n = 3 in [60]; n = 106 in [47] for a population study). In sea bass, Anastasiadi and Piferrer [83] previously reported a study that used 27 samples and as many libraries to be sequenced while our data were obtained from a unique library preparation. Our modi ed epiGBS protocol provides a considerable amount of information, certainly at a reasonable cost, to decipher methylation landscapes of sea bass or other species.…”

“…ROBO3 is involved in the immune response, but also implied in early neurogenesis [178], as well as NPAS3 [179]. With BMP3 [180], FURIN [181]; NOL4B [182], and Myf5 [183,184], most of these genes are engaged in the development of the anterior region and/or the craniofacial skeleton which is modi ed during sea bass farming [83]. This suggests that methylation patterns observed in sea bass could also potentially rely on the ontogenetic regulation of a particular phenotype between pre-and post-stress sh, rather than being directly related to the stress challenge.…”

“…It has been extensively studied over the last three decades, for both natural and farmed populations (reviewed in [75]). This includes the sequencing of its genome [76] and an increasing number of epigenetic studies [77][78][79][80][81][82][83][84]. The stress response of European sea bass remains evaluated using blood parameters that have been shown to re ect multiple components of its stress response [16,85], despite authors have proposed alternatives [86,87].…”