Epigenetics Rising in Consciousness of Geneticists, Embryologists

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Posted on July 27, 2009 in Genetics, Health, Human Body

The old story of genetics was that all the information is in genes, and when sperm and egg unite, it’s only the combination of genes from parents that affect the offspring.  That view has been under challenge for years now as geneticists and embryologists find more and more evidence for additional heritable factors that affect development of the embryo and the life of the offspring.
    It should have been obvious that more than genes unite at conception.  Both egg and sperm are much more than sets of naked genes.  Nature reported that human sperm contains protein factors that guide and direct the embryo.1  Researchers primarily at Howard Hughes Medical Institute found that distinctive chromatin packages genes for embryo development.  Prior to this, they said, “the epigenetic contributions of sperm chromatin to embryo development have been considered highly limited.”  They found numerous heritable factors:

Here we show that the retained nucleosomes are significantly enriched at loci of developmental importance, including imprinted gene clusters, microRNA clusters, HOX gene clusters, and the promoters of stand-alone developmental transcription and signalling factors.  Notably, histone modifications localize to particular developmental loci.  Dimethylated lysine 4 on histone H3 (H3K4me2) is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX clusters, certain noncoding RNAs, and generally to paternally expressed imprinted loci, but not paternally repressed loci.  Notably, trimethylated H3K27 (H3K27me3) is significantly enriched at developmental promoters that are repressed in early embryos, including many bivalent (H3K4me3/H3K27me3) promoters in embryonic stem cells.  Furthermore, developmental promoters are generally DNA hypomethylated in sperm, but acquire methylation during differentiation.  Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators.

So it’s not just the gift of DNA; it’s the packaging.  “We provide several lines of evidence that the parental genome is packaged and covalently modified in a manner consistent with influencing embryo development.”  The factors in both egg and sperm affect “developmental decisions and imprinting patterns.”
    In a related topic, Science Daily said that the rise in awareness of epigenetics among researchers is blurring the line in the old nature-nurture debate.  For instance, doctors used to think that having a certain mutation guaranteed a patient will have a genetic disease.  Other factors, though, such as a mother’s diet, can affect the outcome: “epigenetic factors play a surprisingly large role in the disease risk that gets passed down through the generations,” the article said.  While permanent genetic mutations are the largest factor, “what is not often explained is that less permanent changes to our DNA also significantly influence our risk for disease,” said Mark Johnston, editor of Genetics.  “We tend to view disease risk as a tug of war between nature and nurture, but this study shows that nature and nurture are more closely related than we had imagined.”

1.  Hammoud et al, “Distinctive chromatin in human sperm packages genes for embryo development,” Nature 460, 473–478 (23 July 2009) | doi:10.1038/nature08162.

It should be noted that nature vs nurture is an example of the either-or fallacy.  Some evolutionary psychologists agree (see PhysOrg): they called for “tossing out the nature-nurture debate, which they say has prevailed for centuries in part out of convenience and intellectual laziness.”  Can you think of other factors that should be added to the equation?  How about intelligence and choice?  Without those, it renders human beings as mere determined products of physical and environmental factors.  Your genetics and environment are not forcing you to read these words right now.  Think about that.  There – you made another choice.
    Epigenetics is poised to mount another major assault on evolutionary theory.  One of the points made in the upcoming film Darwin’s Dilemma* is that epigenetic factors pile difficulty upon difficulty for Darwin, because evolutionary theory needs to account not only for genetic information in DNA, but the epigenetic information that controls development.  There are many factors beyond the gene library that determine a body plan.  What orchestrates and choreographs the orderly localization of cell types in a developing embryo?  What manages their differentiation?  What commits them to the roles they will play?  We are only beginning to understand these higher-order programs.  If neo-Darwinists were hard-pressed to explain the genetic code by the accumulation of mutations filtered by natural selection, wait till they have to account for the epigenetic code.
*Scheduled for release in mid-September: see Illustra Media.


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