pubmed.ncbi.nlm.nih.gov

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

  • ️Tue Jan 01 2019

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

Dafni Anastasiadi et al. Mol Biol Evol. 2019.

Erratum in

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.

Keywords: animal domestication; developmental processes; domestication syndrome; epigenetics; epimutation, transgenerational effects, glutamate receptors; neural crest.

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

PubMed Disclaimer

Figures

<sc>Fig</sc>. 1.
Fig. 1.

DNA methylation changes in early domesticate versus wild European sea bass. (A) Genome-wide distribution of DMRs; red, hypermethylation; green, hypomethylation. (B) Details of annotated genes on chromosome 4 containing DMRs in tissues derived from the ectoderm (brain; blue), paraxial mesoderm (muscle; light green), intermediate mesoderm (testis; green), and endoderm (liver; red). (C) GO term enrichment of genes that contain DMRs. The length of the bar indicates the log10-transformed P value of the enrichment and the color scale indicates the amount (in percent) of genes associated with the specific GO term as compared with the total number of genes with DMRs.

<sc>Fig</sc>. 2.
Fig. 2.

Epimutations established during early development. (A) Absolute (green) and relative (red) number of genes with DMRs established during gastrulation, the latter shown as a percentage of the total number of genes with DMRs in adults. The dotted line indicates the mean of the relative number and the shaded area includes the range. (B) GO term enrichment of genes that contain DMRs. The most significantly enriched GO terms, related to development, are ranked according to the decreasing order of −log10-transformed P value of the enrichment and colored according to the percentage of genes that contain DMRs and that are members of each GO category. (C) Enrichment of tissues where the genes with DMRs are expressed. The most significantly enriched tissues are ranked according to the combined z-score as calculated by the Enrichr tool and colored according to the −log10-transformed adjusted P value of the enrichment.

<sc>Fig</sc>. 3.
Fig. 3.

Influence of the farming environment on genes interacting with the ECM and neurotransmitters. Distribution of CpG methylation in wild (red, W) and farmed (blue) sea bass during gastrulation (E) and in adult tissues (F) inside the DMRs of adamts9 (A), col18a1 (D), and gria4a (F). Mean methylation of CpGs around the DMRs of adamts9 in muscle (B), col18a1 in testis (E), and gria4a in brain (G). Differential gene expression of adamts9 is also shown (C). The extent of DMRs is highlighted with gray shading and the CpGs are arbitrarily numbered. Differences in expression are shown with the following equivalence: ***P adjusted <0.001.

<sc>Fig</sc>. 4.
Fig. 4.

Epimutations as a consequence of the farming environment associate with genetic changes in the sea bass after 25 years of domestication. (A) DMCs in early domesticate versus wild sea bass overlap with on-the-spot SNPs in two sea bass populations after 25 years of selective breeding (Bertolini et al. 2016). The number of overlaps of the two genomic sites is shown and tested via permutations. The shaded grey area shows the number of overlaps of randomized regions with the mean represented by the black bar. The green line represents the actual number of overlaps of SNPs with DMCs and the double arrow its distance from the significance limit in red. The significance of the association is indicated by the z-score and the P value. (B) Schematic representation inside the DMR of cadherin family member 9 of a CpG in wild sea bass that was found hypermethylated (red lollipop) in early domesticates (Fearly) and converted into a TG after 25 years of selective breeding (Fsel).

Similar articles

Cited by

References

    1. Akalin A, Kormaksson M, Li S, Garrett-Bakelman FE, Figueroa ME, Melnick A, Mason CE.. 2012. methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles. Genome Biol. 1310:R87.. - PMC - PubMed
    1. Alexa A, Rahnenfuhrer J.. 2009. Gene set enrichment analysis with topGO. Bioconductor Improv, 27. https://bioconductor.org/packages/release/bioc/vignettes/topGO/inst/doc/... last accessed July 05, 2019.
    1. Anastasiadi D, Esteve-Codina A, Piferrer F.. 2018. Consistent inverse correlation between DNA methylation of the first intron and gene expression across tissues and species. Epigenet Chromatin 111:37. - PMC - PubMed
    1. Anastasiadi D, Vandeputte M, Sánchez-Baizán N, Allal F, Piferrer F.. 2018. Dynamic epimarks in sex-related genes predict gonad phenotype in the European sea bass, a fish with mixed genetic and environmental sex determination. Epigenetics 139:988–1011. - PMC - PubMed
    1. Andrews S. 2010. FastQC: a quality control tool for high throughput sequence data. http://www.bioinformatics.babraham.ac.uk/projects/fastqc/. last accessed July 05, 2019.

Publication types

MeSH terms