Transgenerational Inheritance Of Phenotypic Variation Research Articles

Intrinsically disordered BMP4 morphogen and the beak of the finch: Co-option of an ancient axial patterning system

Darwin's finches, with the primary diversity in the shape and size of their beaks, represent an excellent model system to study speciation and adaptive evolution. It is generally held that evolution depends on the natural selection of heritable phenotypic variations originating from the genetic mutations. However, it is now increasingly evident that epigenetic transgenerational inheritance of phenotypic variation can also guide evolutionary change. Several studies have shown that the bone morphogenetic protein BMP4 is a major driver of beak morphology. A recent study explored variability of the morphological, genetic, and epigenetic differences in the adjacent “urban” and “rural” populations of two species of Darwin's finches on the Galápagos Islands and revealed significant changes in methylation patterns in several genes including those involved in the BMP/TGFß pathway in the sperm DNA compared to erythrocyte DNA. These observations indicated that epigenetic changes caused by environmental fluctuations can be passed on to the offspring. Nonetheless, the mechanism by which dysregulated expression of BMP4 impacts beak morphology remains poorly understood. Here, we show that BMP4 is an intrinsically disordered protein and present a causal a link between epigenetic changes, BMP4 dysregulation and the evolution of the beak of the finch by natural selection.

Differential DNA methylation in somatic and sperm cells of hatchery vs wild (natural-origin) steelhead trout populations.

Environmental factors such as nutrition, stress, and toxicants can influence epigenetic programming and phenotypes of a wide variety of species from plants to humans. The current study was designed to investigate the impacts of hatchery spawning and rearing on steelhead trout (Oncorhynchus mykiss) vs the wild fish on a molecular level. Additionally, epigenetic differences between feeding practices that allow slow growth (2 years) and fast growth (1 year) hatchery trout were investigated. The sperm and red blood cells (RBC) from adult male slow growth/maturation hatchery steelhead, fast growth/maturation hatchery steelhead, and wild (natural-origin) steelhead were collected for DNA preparation to investigate potential alterations in differential DNA methylation regions (DMRs) and genetic mutations, involving copy number variations (CNVs). The sperm and RBC DNA both had a large number of DMRs when comparing the hatchery vs wild steelhead trout populations. The DMRs were cell type specific with negligible overlap. Slow growth/maturation compared to fast growth/maturation steelhead also had a larger number of DMRs in the RBC samples. A number of the DMRs had associated genes that were correlated to various biological processes and pathologies. Observations demonstrate a major epigenetic programming difference between the hatchery and wild natural-origin fish populations, but negligible genetic differences. Therefore, hatchery conditions and growth/maturation rate can alter the epigenetic developmental programming of the steelhead trout. Interestingly, epigenetic alterations in the sperm allow for potential epigenetic transgenerational inheritance of phenotypic variation to future generations. The impacts of hatchery exposures are not only important to consider on the fish exposed, but also on future generations and evolutionary trajectory of fish in the river populations.

Environmentally Induced Epigenetic Transgenerational Inheritance and the Weismann Barrier: The Dawn of Neo-Lamarckian Theory.

For the past 120 years, the Weismann barrier and associated germ plasm theory of heredity have been a doctrine that has impacted evolutionary biology and our concepts of inheritance through the germline. Although August Weismann in his 1872 book was correct that the sperm and egg were the only cells to transmit molecular information to the subsequent generation, the concept that somatic cells do not impact the germline (i.e., the Weismann barrier) is incorrect. However, the doctrine or dogma of the Weismann barrier still influences many scientific fields and topics. The discovery of epigenetics, and more recently environmentally induced epigenetic transgenerational inheritance of phenotypic variation and pathology, have had significant impacts on evolution theory and medicine today. Environmental epigenetics and the concept of epigenetic transgenerational inheritance refute aspects of the Weismann barrier and require a re-evaluation of both inheritance theory and evolution theory.

Developmental origins of epigenetic transgenerational inheritance.

Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective.

Epigenetics and the evolution of Darwin's Finches.

The prevailing theory for the molecular basis of evolution involves genetic mutations that ultimately generate the heritable phenotypic variation on which natural selection acts. However, epigenetic transgenerational inheritance of phenotypic variation may also play an important role in evolutionary change. A growing number of studies have demonstrated the presence of epigenetic inheritance in a variety of different organisms that can persist for hundreds of generations. The possibility that epigenetic changes can accumulate over longer periods of evolutionary time has seldom been tested empirically. This study was designed to compare epigenetic changes among several closely related species of Darwin’s finches, a well-known example of adaptive radiation. Erythrocyte DNA was obtained from five species of sympatric Darwin’s finches that vary in phylogenetic relatedness. Genome-wide alterations in genetic mutations using copy number variation (CNV) were compared with epigenetic alterations associated with differential DNA methylation regions (epimutations). Epimutations were more common than genetic CNV mutations among the five species; furthermore, the number of epimutations increased monotonically with phylogenetic distance. Interestingly, the number of genetic CNV mutations did not consistently increase with phylogenetic distance. The number, chromosomal locations, regional clustering, and lack of overlap of epimutations and genetic mutations suggest that epigenetic changes are distinct and that they correlate with the evolutionary history of Darwin’s finches. The potential functional significance of the epimutations was explored by comparing their locations on the genome to the location of evolutionarily important genes and cellular pathways in birds. Specific epimutations were associated with genes related to the bone morphogenic protein, toll receptor, and melanogenesis signaling pathways. Species-specific epimutations were significantly overrepresented in these pathways. As environmental factors are known to result in heritable changes in the epigenome, it is possible that epigenetic changes contribute to the molecular basis of the evolution of Darwin’s finches.