More Than Just the Genome: Epigenetics

More Than Just the Honey Bee Genome: Does Epigenetics Play a Role?

Bee Culture (May) Vol. 136: 17-19

Malcolm T. Sanford

http://apis.shorturl.com

The sequencing of the honey bee genome is expected to provide a series of potential benefits as I described first in April 2003 with a follow up article in December 2006. In the former article, I stated that findings revealed that the honey bee genome shows greater similarities to those of vertebrates than Drosophila and Anopheles, for genes involved in circadian rhythms, RNAi, and DNA methylation among others.

And, I said in December 2006: “It appears that the honey bee genome evolved more slowly than the genomes of the fruit fly and malaria mosquito. One consequence of that slower evolutionary pace is that the bee genome contains versions of some important mammalian genes that have been lost from the fruit fly and mosquito genomes. Is the honey bee more slowly evolving than most organisms, or have the fly and mosquito (both members of the same order, Diptera) evolved faster? And if it’s the former, is that because of the bee’s social lifestyle? These questions can only be answered with genome sequences for more species, and thankfully, more are on the way.”

At this juncture, it might be worth defining more clearly the “genome sequences” noted above. DNA functions as life’s universal dictionary: It acts as a template, making information available (by a process called “transcription”) to an RNA template, which is called messenger RNA (mRNA). The mRNA determines (translates) the order of amino acids to make specific proteins. The “genetic code,” therefore, is a set of rules or instructions where DNA determines the order of amino acids to make proteins via mRNA. This is accomplished by the sequence of the nucleic acids’ respective units or nucleotides.

Only four nucleotides constitute the nucleic acids DNA and mRNA. Each nucleotide is characterized by a specific compound known as a “base.” These bases are intimately associated with each other and must always be paired in a specific way, known as base pairs. Finding out the number and particular sequence of base pairs in a DNA chain allows scientists to not only examine, but also manufacture a specific organism’s genetic code. Another way to look at this process is to visualize the base pairs as letters that are strung together into words, which then form sentences that in their entirety are the instructions for running an organism’s life, its genome.

Most folks at some level are familiar with the above and for many the story seemed to end there; that organisms were stuck with the DNA they were born with (i.e. cards they were dealt in the genetic hand). But as in so much of biology, there’s more. That is described in a topic that many people have not heard about, including this author, until he was told about it by an up-and-coming queen producer. It’s called epigenetics. We’ll all be hearing more about this in the future. I hope you will remember that the first time you heard about this important field was in these pages.

Dubbed “The Science of Change,” epigenetics is implicated in a wide variety of human illnesses and behaviors, including many cancers and respiratory, cardiovascular, reproductive, autoimmune, and neurobehavioral illnesses. Known or suspected drivers behind epigenetic processes include heavy metals, pesticides, diesel exhaust, tobacco smoke, polycyclic aromatic hydrocarbons, hormones, radioactivity, viruses, bacteria, and basic nutrients.¹

The word epigenetic means “in addition to changes in genetic sequence.” The term has evolved to include any process that alters gene activity without changing the DNA sequence, and leads to modifications that can be transmitted to daughter cells (although experiments show that some epigenetic changes can be reversed). Many types of epigenetic processes have been identified--they include methylation, acetylation, phosphorylation, ubiquitylation, and sumolyation. Epigenetic processes are natural and essential to many organism functions, but if they occur improperly, there can be major adverse health and behavioral effects. Other epigenetic mechanisms and considerations are likely to surface as study proceeds, and it is likely there will continue to be debate over exactly what the term means and what it covers.

One of the more studied epigenetic processes is DNA methylation, the addition of a methyl group (CH₃) to the DNA molecule. Again, note that this may interfere with subsequent transcription, but will not change the genomic sequence. Nevertheless, importantly, it will be usually passed on to daughter cells (the next generation). This has been implicated in Rett syndrome in humans, usually caused (95% or more) by a de novo mutation in the child (so it is inherited from a genotypically normal mother). Rett syndrome affects one in every 12,500 female live births by age 12 years and is an almost entirely female disease.² In other situations, it can lead to abnormal growth of tissues, overgrowth of abdominal organs, low blood sugar at birth and cancers. Similarly, in the imprinting disorder Prader-Willi syndrome, abnormal epigenetics causes short stature and mental retardation.³

Plants are also affected by DNA methylation. “This sort of mechanism is thought to be important in cellular defense against RNA viruses and/or transposons both of which often form a double-stranded RNA that can be mutagenic to the host genome. By methylating their genomic locations, through a still-poorly-understood mechanism, they (genes) are shut off and are no longer active in the cell, protecting the genome from their mutagenic effect.”⁴

The addition of methyl groups to the DNA backbone is also used to distinguish the gene copy inherited from the father and that inherited from the mother. This process is called “imprinting,” as noted above in Prader-Willie syndrome. It doesn’t follow traditional laws of genetics, which describe the inheritance of traits as either dominant or recessive, where both parental copies are equally likely to contribute to the outcome. The impact of an imprinted gene copy, however, depends only on which parent it was inherited from. For some imprinted genes, the cell only uses the copy from the mother to make proteins, and for others only that from the father.⁵

“Centuries ago, mule breeders in Iraq noted that crossing a male horse and a female donkey created a different animal than breeding a female horse and a male donkey. In the mid 1980s, scientists studying mice discovered that inheritance of genetic material from both a male and a female parent was required for normal development. The experiments also revealed that the resulting abnormalities changed depending on whether the inherited genetic material was all male in origin or all female.

“Why imprinting evolved in animals is unclear, but one hypothesis is that it represents a genetic ‘battle of the sexes,’ since many imprinted genes regulate embryonic growth. Maternally-expressed imprinted genes (for which the copy from mom is always used) usually suppress growth, while paternally expressed genes usually enhance growth. The ‘battle of the sexes’ hypothesis is partly based on studies in animals that suggest growth-promoting imprinted genes help ensure the continuation of the father's genes, a particularly important issue for species in which more than one male can contribute to a single litter of offspring. The mother, however, is more interested in maintaining her own health, biologically speaking, and hence her genes ‘fight’ the paternal genes and limit the size of the embryo or fetus.”⁶

Does this remind readers of any particular organism? How about the polyandrous honey bee? Paternity matters in honey bees in several ways. First as seen in these pages and elsewhere, it has been revealed in study after study that diversity makes a big difference in colony productivity and that it is achieved via the contribution of a number of drones (the more the better?) to a queen’s sperm supply. It also matters when it comes to Africanization of European honey bees;. studies appear to show that drones are far more important in the process than queens. It only takes the influence of a few African drones to produce an over-defensive colony.

There's also evidence that some imprinted genes may play a role in social behavior, particularly in nurturing situations. Mother rats that are good moms, for example, can permanently change the way the genes of their offspring act, causing their pups to be calmer throughout adulthood.

The following appears in a recent abstract with respect to sociological study in humans: “The methods and theoretical repertoire of the biomedical sciences are undergoing rapid change fuelled, first and foremost, by advances in genomics and molecular biology. Advances in the understanding of epigenetic regulation have begun to fundamentally change notions of inheritance and development and to differentiate the central dogma of genetics (DNA makes RNA makes Protein), with significant implications for notions of inter and intra-generational responsibility and biographical time regimes. The incorporation of ‘things social’ into medical domains is being taken to a new level of significance, fuelled by a number of fundamental shifts in medical reasoning and practice. The social sciences’ current focus on (epi)genetics can only be a starting point for a broader interdisciplinary agenda to better understand the pathways through which ‘the social and cultural’ enters the body.”⁷

The idea that environment (nurture) does impact genetics (nature) is the basis for the development of the field of epigenetics by two iconoclastic scientists. Their stated mission was to find out what is really at the heart of this interaction.

“Together, they discovered that our genetic code, the actual sequential structure of our DNA, can pretty much shrug off the influence of any external environmental factors, short of massive radiation. However, the expression of individual genes within that sequence can be permanently altered by such seemingly innocuous influences as diet or how others treat us. Once triggered, a group of molecules called a methyl group attaches itself to the control centre of a gene, permanently switching on or off the manufacture of proteins that are essential to the workings of every cell in our body. In most tumours, this DNA methylation pattern has been knocked awry, leading to a gene being completely deactivated or triggered to abnormally high activity.

“Now, scientific evidence is emerging that these externally driven changes in the behaviour of our genes might be passed down through the generations. For example, recent research has demonstrated that the sons of men who began smoking before puberty were more prone to obesity. All of a sudden, we're staring personal responsibility in the face. Not only can our bad habits or noble attempts at clean living permanently change the way our genes act within us, they could very well have a significant impact on the quality of our children's lives.”⁸

This also contributes to a reconsideration of an old view of evolution proposed by Lamarck and discredited over the years as Darwin’s ideas of natural selection took hold. It proposed that individual efforts during the lifetime of the organisms were the main mechanism driving species to adaptation, as they supposedly would acquire adaptive changes and pass them on to offspring. A proponent was Ivan Pavlov, who claimed to have observed similar phenomena in animals being subject to conditioned reflex experiments. He saw that with each generation, the animals became easier to condition.⁹ So-called NeoLamarckism has been given impetus with discoveries of epigenetic phenomena. But although the reality of epigenetic inheritance is not doubted (countless experiments have validated it) the significance to the evolutionary process remains uncertain.¹⁰

Returning to honey bees as noted in the first part of this article, their genome is much like that of vertebrates. In addition, their sociality is highly developed and there is already evidence that the haplo-diploid situation with regard to the “battle of the sexes” fits with epigenetic theory. All this points to the fact that the effects of epigenetics cannot be ignored when beekeepers manage or scientists study the honey bee. Genetic analysis of Apis mellifera is no longer just about the genome. Epigenetics and the resultant epigenome must be taken into account as well. Both beekeeping and bee research just got a lot more complicated.

References: (All URLs accessed February 12, 2008).