DNA methylation networks underlying mammalian traits.

Using DNA methylation profiles (n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.

Comparative embryology of Delphinapterus leucas (beluga whale), Balaena mysticetus (bowhead whale), and Stenella attenuata (pan-tropical spotted dolphin) (Cetacea: Mammalia).

Embryogenesis of cetaceans (whales, dolphins, porpoises) is best known in Stenella attenuata, the pan-tropical spotted dolphin, based on a remarkably complete and well-studied prenatal ontogenetic series. Our study expands understanding of cetacean embryology by adding two additional cetacean taxa: the beluga whale (Delphinapterus leucas, Odontoceti), and the bowhead whale (Balaena mysticetus, Mysticeti). We identify key features that characterize these taxa at specific stages and highlight heterochrony between the odontocetes and mysticetes. The toothed whales are more similar in developmental timing to each other than either is to Balaena. The two odontocete taxa, Stenella and Delphinapterus, share similar developmental trajectories while early Balaena specimens differ from the odontocetes. This developmental variation proves challenging to ascribe to the existing Carnegie staging system. Most notably, flippers, hindlimbs, and flukes all provide morphological traits for characterization within the Carnegie staging system. A presomitic Delphinapterus embryo is also described. This study applies the Carnegie staging system to two more cetacean taxa and forms a framework for future research on cetacean developmental genetics and the modeling of fetal growth.

Linking gene expression and phenotypic changes in the developmental and evolutionary origins of osteosclerosis in the ribs of bowhead whales (Balaena mysticetus).

Bowhead whales are among the longest-lived mammals with an extreme lifespan of about 211 years. During the first 25 years of their lives, rib bones increase in mineral density and the medulla transitions from compact to trabecular bone. Molecular drivers associated with these phenotypic changes in bone remain unknown. This study assessed expression levels of osteogenic genes from samples of rib bones of bowheads. Samples were harvested from prenatal to 86-year-old whales, representing the first third of the bowhead lifespan. Fetal to 2-year-old bowheads showed expression levels consistent with the rapid deposition of the bone extracellular matrix. Sexually mature animals showed expression levels associated with low rates of osteogenesis and increased osteoclastogenesis. After the first 25 years of life, declines in osteogenesis corresponded with increased expression of EZH2, an epigenetic regulator of osteogenesis. These findings suggest EZH2 may be at least one epigenetic modifier that contributes to the age-related changes in the rib bone phenotype along with the transition from compact to trabecular bone. Ancient cetaceans and their fossil relatives also display these phenotypes, suggesting EZH2 may have shaped the skeleton of whales in evolutionary history.