Watched a fascinating program on epigenetics and the epigenome, Ghost in Your Genes. It was originally broadcast last summer, but I missed it. Here is a short introduction:
Conrad Waddington, originally defined the term epigenetics as 'the interactions of genes with their environment that bring the phenotype into being'. Today, the term is used to describe the study of heritable changes in genome function that occur without a change in DNA sequence. This includes; the study of how patterns of gene expression are passed from one cell to its descendants, how gene expression changes during the differentiation of one cell type into another, and how environmental factors can change the way genes are expressed. There are far-reaching implications of epigenetic research for agriculture and for human biology and disease, including our understanding of stem cells, cancer and ageing.
http://www.epigenome-noe.net/aboutus/epigenetics.php
While the PBS program concentrated on pathology as does the above, the much more interesting aspect to the function of epigenetics is its implications for evolution.
It always struck me as a fault that tools as crude as mutations and natural selection no matter how finely nuanced could account for the rich diversity and sophistication we find in the world of plants and animals. The study of epigenetics unveils a whole new and potentially much larger realm of systems through which evolutionary processes in conjunction with the environment give rise to richness of biological systems. Here is the key quote:
``Gene expression, chromosome segregation, DNA replication, repair, and recombination all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed epigenetic mechanisms that considerably extend the information potential of the genetic code. Thus, one genome can generate many 'epigenomes', as the fertilised egg progresses through development and translates its information into a multitude of cell fates.''
In the program, several researchers studied the records of a remote village in Sweden and discovered among other things, that boys who lived through famines in their late childhood between about ten and thirteen had grandsons who lived longer than average. Meanwhile, girls born to mothers during a famine had granddaughters who lived relatively shorter lives.
The theory is that ovaries and eggs are formed during fetal development in females. In males, cells in the testis that produce sperm are formed much later sometime during the onset of puberty or adolescence. So, then the difference of timing in the origin of female and male germ cell development create differences in the response to similar environmental factors that bring the phenotypes into being. The importance is that these epigenetic phenomenon are inherited. The mode of inheritance is through the regulatory system carried in the germ cell DNA. In girls the ovum and its future DNA compliment are created during fetal development. In boys, sperm and its compliment DNA are created later at onset of reproductive age.
Okay, so what difference does that make? They didn't go into this in the program, but the difference is that the timing of puberty can be influenced directly by the environment by altering the complicated hormone systems of the body. These alterations are known to happen through diet deficiencies and heavy physical stress. Famine delays puberty in both male and females. In females that timing doesn't seem to effect the ovum DNA since it is already formed. In males, it very well might. The Sweden study implies it does and that effect may be beneficial at least in terms of aging and possibly disease resistances.
Fifteen years ago when I was studying the genetic regulatory system in plants, the labs were just beginning to understand the molecular details of the transcription and regulation system which basically runs maintenance routines on DNA repairing breaks, cutting bad joins and returning them to proper arrangement turning on some genes and turning off others. It is this system, this maintenance and repair system that goes on all the time in the phenotypic cellular expression that has the potential for environmental influence. Once influenced and altered, some of the alterations are then passed on through cell divisions and through the production of germ cells.
Here is a NYT article:
http://www.nytimes.com/2009/02/24/science/24chromatin.html? _r=1&th&emc=th
This is an illustration of the potential complexity involved:
http://www.nytimes.com/imagepages/2008/11/11/science/ 20081111_EPIGENETICS_GRAPHIC.html?ref=science
Here is the key paragraph:
``How is the structure of the epigenome determined? The basic blueprint for the epigenomes needed by each cell type seems to be inherent in the genome, but the epigenome is then altered by other signals that reach the cell. The epigenome is thus the site where the genome meets the environment.''
Here is another that bares on the story of the Swedish researchers:
``A family of enzymes called sirtuins monitors the nutritional state of the cell, and one of them removes a specific mark from the chromatin, providing a possible route for the genome to respond to famine conditions.''
Beside the crotch, the other great area of my interest of course is the development of the brain and central nervous system. Again I am more interested in the evolutionary implications rather than the pathologies. So, getting straight to the point. We descended from highly socialized primates with complex behaviors and of course the mating and social lives locked into development and psycho-social mediators of our hormone systems and in turn ... now evidently the effect of those on our epigenenome.
The above developments in epigenetic studies means that it might be possible to sketch our own evolutionary history in much more detail and nuance than ever before. When these studies are combined with the sorts of detail that we now can reconstruct about ancient ecologies and environments, well, just wow.
For example, the timing of human development with a lengthened childhood has obvious adaptive advantages, in the increase of time for learned behavior and acquisition of knowledge and skills. But it is by no means obvious how such a delayed maturity got started in the first place. Perhaps a more thorough knowledge and understanding of the epigenetics of our maturation system will tell us. Our maturation is tightly controlled by our complex hormonal systems and their interactions with the brain chemistry and the environment.
With cross comparisons over time and space and human populations looking at both very slight genetic differences combined with epigenetic difference we might get a much more detailed and much richer picture of the human evolutionary landscape, and well the broader systems of evolution. From only one night's reading it seems the evolution of the epigenenomic system is not well understood...
For example, think about the implications of the epigenenome combined with Gould's punctuated equilibrium hypothesis. We know that certain kinds of environmental changes have lead to very fast evolutionary changes. We now have an additional potential mechanism by which we can explain those periods of speed up and slow down in the evolutionary record.
Waddington has been around for a long time and I saw illustrations for his work back in the 1970s. But the basic implication was that as time goes on, the cell lines become more and more fixed. An embryonic stem cell line becomes a liver cell and doesn't return to stem cell.
What's new in the recent developments is while all that might be true, the epigenetic phenomenon that create this landscape, is itself alterable by environmental conditions and that changes at that level can be inherited. Here are some illustrations of his work with a short description:
http://www.nature.com/nrg/journal/v3/n11/fig_tab/nrg933_F3.html
CG