In the last blog we saw how cells keep track of invading DNA and use that information to target copies for incorporation in silent chromatin. The ability of cells to silence mobile genetic elements and other invading DNAs is a key epigenetic control process maintaining genome stability in normal times, when growth and reproduction proceed smoothly. The silent elements and other natural genetic engineering agents do not disturb a genome that is functioning well.
But what happens when the going gets tough? Do the tough get going in the genome, generating change to get out of trouble? The answer is: Yes, they do. We know that all kinds of stress conditions activate natural genetic engineering processes. These stresses range from DNA damage, exposure to various poisons and lack of nutrients to infection, dehydration and too much salt.
Almost 30 years ago, Barbara McClintock recognized genome responses to challenge in her Nobel Prize speech:
In the future attention undoubtedly will be centered on the genome, and with greater appreciation of its significance as a highly sensitive organ of the cell, monitoring genomic activities and correcting common errors, sensing the unusual and unexpected events, and responding to them, often by restructuring the genome. We know about the components of genomes that could be made available for such restructuring. We know nothing, however, about how the cell senses danger and instigates responses to it that often are truly remarkable.
Since McClintock's time, we have learned that a great deal of cell sensing involves the epigenetic regulation of mobile elements and other aspects of genome function. The same kind of stresses that activate natural genetic engineering lead to major changes in epigenetic chromatin formatting: loss of DNA methylation and alteration of histone modifications.
As I remarked in the first blog on epigenetics, many environmental stresses lead to multigenerational inherited epigenetic changes. This is consistent with multigenerational genome instabilities induced by stresses such as viral infection.
Among the life history events which lead to genome instabilities and epigenetic modifications are unusual mating events, such as interspecific hybridization. Although interspecific hybridizations have been recognized as critical events by some evolutionists for a long time (Stebbins 1951; Anderson 1954), their importance has not been widely appreciated by the general public or molecular biologists.
DNA sequencing uncovered whole genome duplications at key transition points in evolution of organisms from bacteria and yeasts to flowering plants and vertebrates. This striking and widely unexpected finding caused the molecular community to pay more attention to hybridization because it is often associated with genome doubling.
We know about the connection between unusual mating events and epigenetic control most clearly in the related phenomenon known as "hybrid dysgenesis" in animals (Drosophila, mice and marsupials).
Hybrid dysgenesis has a fascinating history (Bregliano 1983). It originated in attempts to investigate the population biology of wild Drosophila by carrying out genetic analysis of flies captured from their natural habitats, such as garbage cans. When wild flies were mated with laboratory stocks established in the early 20th Century, the crosses often were not successful or produced aberrant results. The poor outcomes dictated the name "dysgenesis" (i.e., reproductive disfunction).
In many cases, before hybrid dysgenesis became a recognized phenomenon in the 1970s, investigators sometimes blamed laboratory personnel for the problems. I recall discussing this topic with a fellow PhD student and famous Drosophila geneticist, Michael Ashburner. We speculated on how many technicians lost their jobs because a still unknown natural process was at work.
Investigation of hybrid dysgenesis revealed two essential components to the phenomenon. One was the acquisition or reactivation of mobile elements in the chromosomes of wild flies. The P factor transposon is the prototype for such an element. P represents "paternal" because P factors came from the male in the typical dysgenic mating.
The P factor was acquired by wild Drosophila sometime after the laboratory strains were established. The transposon spread through the genomes of populations across the globe following World War II, apparently aided by international trade in fruits that served as hosts to the flies.
P factors preferentially insert and mutate the Drosophila X-linked singed locus, which affects bristle shape, a trait that can be seen with a magnifying glass. This mutagenic preference made it possible to locate the interface between populations with and without the transposon simply by finding zones with a high frequency of singed mutant flies. Misha Golubovsky did this in the 1970s and was able to trace the spread of P factors across the Siberian forests.
The second component of hybrid dysgenesis was a more mysterious property of the M ("maternal") strain called "cytotype." The egg cells of the M strain females in dysgenic crosses had a cytotype that was permissive for P factor activation, while the egg cells of wild P strains had a repressive cytotype. The nature of cytotype remained mysterious until just a few years ago, when it was definitively correlated with genetic loci encoding piRNAs that direct epigenetic silencing of the incoming P factors.
We are still far from understanding epigenetic and genome destabilization that accompany interspecific hybridizations. It is reasonable to hypothesize that each species has its own pattern of epigenetic control, so that natural genetic engineering functions will escape control when gametes with distinct control regimes merge to form a zygote. As we accumulate evidence that whole genome duplications and interspecific hybridization play major roles in evolutionary novelties, the postulated epigenetic conflicts present a new and unexpected place to focus research on molecular control of evolution.
I suggested in my book that ecological crises will deplete populations and thus increase the likelihood of abnormal and interspecific matings. This is a hypothetical contribution to the goal of connecting ecology, the genome and the epigenome with episodes of evolutionary innovation. McClintock predicted that we would focus on how the genome responds to challenge. Clearly, unraveling the molecular basis of epigenetic regulation is an integral part of that revolutionary research agenda.
REFERENCES
Anderson, E., Stebbins, G.L., Jr. (1954). "Hybridization as an evolutionary stimulus." Evolution 8: 378-388.
Bregliano, J., Kidwell, M (1983). Hybrid dysgenesis. Mobile Genetic Elements. J. Shapiro. New York, Academic Press,: 363-410.
Stebbins, J., G.L. (1951). "Cataclysmic Evolution." Scientific American 184(4): 54 -59.
Bacterial Protein Acetylation: the Dawning of a New Age
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907427/?tool=pubmed
The conclusion:
"Bacteria have long been considered simple relatives of eukaryotes. Obviously, this misperception must be modified. From the presence of a cytoskeleton to the packaging of DNA to the existence of multiple posttranslational modifications, bacteria clearly implement highly sophisticated mechanisms to regulate diverse cellular processes precisely. From even a quick scan of the recently generated lists of acetylated proteins, it is clear that many of these processes are likely regulated by acetylation in bacteria and eukaryotes and, almost certainly, archaea as well. If this is the case, then our deep knowledge of bacterial physiology and the power of bacterial genetics and biochemistry should rapidly advance our understanding of protein acetylation and the diverse cellular processes that it regulates."
Thanks for this link. Acetylation is one type of protein modification used in the histone code. We don't know much about bacterial chromatin, which is rather different from eukaryotic chromatin. I expect we will learn soon whether acetylation plays a role in the epigenetic regulation of bacterial genomes.
Acetylation and other covalent protein modifications (phosphorylation, methylation, adenylylation, etc.) are important aspects of cell control and signal transduction. Since these processes are essential to life, it is no surprise to find them in bacteria. We have known about some of them for well over 40 years. It may be that they were actually first discovered in bacteria.
Your comment deserves several replies. These are intended to help keep the discussion focussed on dealing with the biology in as realistic a way as we can with the present state of knowledge.
It is essential to distinguish between what is done by "genes." which are coding sequences of DNA, and by the encoded products. A lot has been written about "gene regulatory networks" as though regions of DNA interacted directly with each other without the participation of all the cellular functions needed for genome information to be expressed.
The response of an intact cell to inputs like hormones and light is a sensory and cognitive process. Describing that as fully as we can is a first step to understanding what the cell as a whole does with the sensory information.
As you correctly point out, different signals work at different time scales. Epigenetic modifications help prepare cells for specialized tasks, like photoreception. Without that preparation, they could not respond usefully. That is one reason it is mistaken to attribute properties of the whole (e.g. a photoreceptor cell) to any individual part (e.g. receptors). The components only do their jobs in context.
As for genes being conscious, remember DNA is inert by itself. Outside properly formatted chromatin and a cell environment full of activities for transcription, replication, signal transduction, etc., the genome does nothing. If we wish to ascribe complex capabilities to living things, we have to choose the appropriate level of description.
I have not argued that epigenetics causes evolution on the macro scale by itself. It plays a role in allowing ecological changes to activate genome restructuring. Ultimately, what we see in the sequence record are the resulting DNA changes.
Epigenetics help us understand the many DNA differences between chimps, humans and other taxonomics groups by showing how major episodes of genome change can occur.
We will never fully comprehend what has happened to create indels, for example, until we can observe them forming in real time. That is why I wrote two earlier blogs encouraging experimental approaches to major genome alterations (http://www.huffingtonpost.com/james-a-shapiro/experimental-evolution-ho_b_1619171.html and http://www.huffingtonpost.com/james-a-shapiro/natural-genetic-engineering_b_1638823.html).
As for preventing species collapse, we don't yet know a lot about that either. Again, we need more real-time observations. My own opinion is that many natural genetic engineering episodes will not prove successful. Complete failure will lead to extinction, and we have many examples in the fossil record.
Personally, I think it is more interesting to find out how the successes happened to generate new species that survived ecological challenge. Those successes are inconceivable on the basis of accidental genome change because the accumulated probabilities become vanishingly small. How do the changes that lead to success accumulate? That is the question.
as an outsider I've often wondered why 'combinatorics' is such a neglected issue in genetics, or have I missed something?
http://blogs.discovermagazine.com/loom/2012/07/19/the-mystery-of-the-missing-chromosome-with-a-special-guest-appearance-from-facebook-creationists
And, an aside, James, I wished you had emulated Carl Zimmer:
http://www.evolutionnews.org/2012/07/we_called_out_d062371.html
Welcome back. Interesting links, but not quite relevant to the topic of epigenetics. More suitable for a discussion of chromosome rearrangements and taxonomic divergences.
Natural genetic engineering is essential for successful chromosome rearrangements. They require coordinated DNA cleavage and splicing events. The events discussed in your first link are excellent examples of active cell involvement in large-scale genome changes in evolutionary diversification. Do you have an explanation that does not involve natural genetic engineering?
You may not be conscious of it, but you are continually asking me to be like other people. I have a great deal of regard for Carl Zimmer and his ability to communicate science. But I prefer to be myself and express my own ways of thinking about the data. That seems to trouble you.
Anyone truly devoted to the progress of science should encourage a diversity of opinions because that's the way we make progress. Is there any particular reason why my having my own views troubles you so much?
Let me know if the following is accurate.
When P-strain males mate with M-strain females, hybrid dysgenesis occurs. This is because the P factor transposons run amok and mess up the genome. However, when P-strain males mate with P-strain females the P factor transposons are held in check, thus resulting in normal offspring.
When this was first observed it was not known what in the P-strain females brought about the 'silencing' of the P factor transposons. Eventually it was discovered that in the genome of the P-strain females were loci encoding piRNAs. The piRNAs in turn have a key role in RNA silencing - post-transcriptional silencing - which destroys the mRNAs which would otherwise result in proteins needed for P factor transposons to 'transpose'. I gather that the loci for the piRNAs occur only in the females thus explaining why the P-strain males alone are not sufficient to avoid hybrid dysgenesis.
The reason the status of the piRNA loci in the females is so important is that the egg contributes virtually all of the nucleus and cytoplasm to the newly fertilized zygote. If the female comes from a strain that has never experienced P factors, then it cannot control them, as you point out. If she comes from a P strain, her eggs have the piRNAs.
It appears to be the case that the germline cells get most of their piRNAs from the egg (and hence from the mother). I do not personally know enough about Drosophila germline development to explain why the piRNAs encoded from the paternal chromosomes are not expressed. It may have to do with how the germline develops or imprinting of the piRNA loci. Wish I knew more, but I think a lot of the developmental details still remain to be worked out.
-Somewhat dissimilar species mate, producing a hybrid with double the number of chromosomes
-Lines of code called P Factors get inserted into the genome from the male
-Those lines of code are "commented out" by epigenetics
-P Factors have the ability to move around (transpose) in the genome, and because they're commented out, new subroutines can be built prior to activation
-In experiments, M strain females from the lab allowed P Factors to merge with their code, but wild female genomes resisted these same P Factors
-Researchers discovered another kind of instruction, called a piRNA, which controls the silencing of the P Factors
When hybrids are formed, cells go through an unstable process of sorting through the redundancies and building new instructions with existing code - per the above.
This has a high failure rate, often producing sterile offspring, but it sometimes successfully engineers an efficient genome for a new fertile species. So hybrids create many fresh opportunities for research into the mechanisms of epigenetics.
Is that about right?
The blurb is basically: cells are complex, creationists are dumb, they'll buy my book.
They won't understand it, partly because they're dumb, and partly because it's very badly edited, or maybe written.
Perhaps because of word limits I was not as clear as could be.
We understand the phenomenon of hybrid dysgenesis in considerable detail. It involves crosses where any one of a number of different kinds of mobile element (P factor transposons, retrotransposons, endogenous retroviruses) enter a zygote where there are no piRNAs directing the formation of silent chromatin keeping those elements in check.
Interspecific hybridization is more complex and much less well understood. We know there are typically three consequences of interspecific hybridization: (1) genome doubling, which is essential for a hybrid to undergo successful meiosis, (2) changes in epigenetic chromatin formatting, mostly losses of inhibitory chromatin, and (3) episodes of genome instability (sometimes more than one generation).
The three consequences of interspecific hybridization all contribute to genomic innovation and are consistent with the correlations found in the DNA sequence record of whole genome duplication and the emergence of novel taxa. We lack detailed knowledge of how and why interspecific hybridization has these well-documented consequences. That subject belongs on the 21st Century research agenda.
Please let me know if I need to amplify more.
I can't help but wonder why the HuffPost approves some of derogatory remarks we see here. I know it's not my fault, but I still feel like apologizing for people who contribute nothing to the discussion but put-downs. The mark of a gentleman is when he can be cordial and respectful even when he fiercely disagrees with his opponent.