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Epigenetics III: Epigenetic Control of Natural Genetic Engineering and Environmental Inputs into Evolutionary Change

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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.