The concerted impact of domestication and transposon insertions on methylation patterns between dogs and grey wolves.
The process of domestication can exert intense trait-targeted selection on genes and regulatory regions. Specifically, rapid shifts in the structure and sequence of genomic regulatory elements could provide an explanation for the extensive, and sometimes extreme, variation in phenotypic traits observed in domesticated species. Here, we explored methylation differences from >24 000 cytosines distributed across the genomes of the domesticated dog (Canis familiaris) and the grey wolf (Canis lupus). PCA and model-based cluster analyses identified two primary groups, domestic vs. wild canids. A scan for significantly differentially methylated sites (DMSs) revealed species-specific patterns at 68 sites after correcting for cell heterogeneity, with weak yet significant hypermethylation typical of purebred dogs when compared to wolves (59% and 58%, P < 0.05, respectively). Additionally, methylation patterns at eight genes significantly deviated from neutrality, with similar trends of hypermethylation in purebred dogs. The majority (>66%) of differentially methylated regions contained or were associated with repetitive elements, indicative of a genotype-mediated trend. However, DMSs were also often linked to functionally relevant genes (e.g. neurotransmitters). Finally, we utilized known genealogical relationships among Yellowstone wolves to survey transmission stability of methylation marks, from which we found a substantial fraction that demonstrated high heritability (both H(2) and h(2 ) > 0.99). These analyses provide a unique epigenetic insight into the molecular consequences of recent selection and radiation of our most ancient domesticated companion, the dog. These findings suggest selection has acted on methylation patterns, providing a new genomic perspective on phenotypic diversification in domesticated species.
Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, 08544, USA.
Ilana
I
Janowitz Koch
Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Michelle M
MM
Clark
Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Michael J
MJ
Thompson
Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, 08544, USA.
Kerry A
KA
Deere-Machemer
Department of Biological Sciences, Wayne State University, Detroit, MI, 48085, USA.
Jun
J
Wang
Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Lionel
L
Duarte
Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, 08544, USA.
Gitanjali E
GE
Gnanadesikan
Yale School of Management, Yale University, New Haven, CT, 06511, USA.
Eskender L
EL
McCoy
Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Liudmilla
L
Rubbi
Yellowstone Center for Resources, National Park Service, Yellowstone National Park, WY, 82190, USA.
Daniel R
DR
Stahler
Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Matteo
M
Pellegrini
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Elaine A
EA
Ostrander
Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Robert K
RK
Wayne
Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, 90095, USA.|Department of Human Genetics and Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Janet S
JS
Sinsheimer
Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, 08544, USA.
Bridgett M
BM
vonHoldt
D000818:Animals; D019175:DNA Methylation; D004251:DNA Transposable Elements; D004285:Dogs / Q000235:genetics*; D000071278:Domestication; D019143:Evolution, Molecular; D040582:Inheritance Patterns; D010375:Pedigree; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D019596:Wolves / Q000235:genetics*
D004251:DNA Transposable Elements
canid; domestication; genome regulation; methylation