Is Eukaryotic DNA Still Living in a Prokaryotic World? How Changing Our Labels Can Change the Way We Think about Genetics

A “housekeeping” gene is a gene which is constitutively or constantly expressed and is necessary for basic cellular functions. “Contingency” genes, on the other hand, produce gene products which are, shall we say, slightly more expendable should a mutation arise. Contingency genes were first identified and have been well-studied in prokaryotes such as bacteria, because these genes, though slightly less vital than your average housekeeping gene product, tend to be highly mutable and offer the organism a rapid means for adaptation to new environmental challenges. For example, many bacterial infections today are growing resistant to antibiotics, a result of rapid genetic adaptation to antibiotic overuse.

Good_housekeeping_1908_08_a

While the term “housekeeping gene” has been used to describe subsets of eukaryotic genes, the term “contingency gene” has really not crossed over [1]. The reason is probably rooted in the limitations of its current definition, the term being defined by two primary characteristics: 1) a high rate of mutability as compared to housekeeping genes, and 2) the mutation’s potential for allowing its carrier to positively adapt to its environment. The problem lies in the fact that it’s really difficult to gauge “positive adaptation” when we study only a single or a few generations of organisms. The concept of “adaptation,” after all, was originally inspired by viewing evidence of ancestral lines over large expanses of time. And so “contingency” has primarily been used in those scenarios in which they’re easiest to identify in short expanses of time, e.g., pathogen-host interactions [1, for review]. Scientists have performed post hoc analyses by selecting those bacteria which have adapted to a given challenge and then found the gene mutations which have correlated with those changes.

In the case of infectious bacteria, especially those which must make their rounds within a single season, rapid adaptation can mean the difference between remaining in the bacterial gene pool and going extinct. But given our ancestral relationship with prokaryotes and the variability in rates of mutations in different genes, might not our own genomes house similar trends in mutation as those in the prokaryotic genomes? Scientists have already identified hundreds of housekeeping genes; perhaps we also have contingency genes as well [2]. We certainly have many genes which could be considered “hypermutable” as compared to the housekeeping genes.

But a label is just a label and has no use if it can’t fulfill some pragmatic purpose, like fostering predictions about gene mutations and how they might relate to the human condition. So what uses might applying the term “contingency genes” to the eukaryotic genome serve?

SOUP

For one, scientists already know something about how contingency genes in prokaryotes mutate. Repetitive sequences are vitally important in producing contingency gene instability– a characteristic not unlike the trinucleotide repeat instability that defines most cases of Fragile X Syndrome for instance [3, 4]. The human genome itself is littered with repetitive sequences just like the prokaryotic genome and are known hotspots for mutations [5, 6, 7]. Coincidence?

Understanding the behavior of mutation-prone genes may also give us a clearer picture as to how DNA has evolved  over the aeons and what techniques it uses, prokaryote and eukaryote alike, to adapt to its environment. Phenotypic plasticity, though capable of creating a myriad of optional traits, can nevertheless be limited by products available to it from its genome. In addition, if these basic techniques are common to both prokaryotes and eukaryotes, it suggests that the division between housekeeping and contingency genes is very old indeed. Though, in reality, this division is undoubtedly nominal and probably more accurately described by a continuum with two tails of extremes. But we may nevertheless glean a great deal of generalizable information from those genes which fall decidedly within the extremes of the genetic spectrum which could subsequently help us understand the causes of mutations throughout.

Understanding how mutations arise can give us a certain means of predicting when they might occur and either a way to treat or even prevent those mutations when their resultant phenotype is less than desirable, e.g., mutations that promote cancer development or neurodevelopmental conditions like Fragile X.

Many aspects of cellular biology may have arisen from mutations in contingency genes, creating larger families of related gene products which have subsequently been used for greater specificity and the dynamic creation of novel cell and tissue groups, such as the central nervous system (CNS). In support of this, Dorus et al. (2004) found that rates of mutation between man and mouse were insignificantly different when comparing housekeeping genes. But when they went on to study a group of genes associated specifically with the CNS, significant differences in numbers of mutations were apparent. This group of scientists also suggested that many of those traits particular to the human CNS have observed a more rapid rate of mutational adaptation as compared to mouse, intimating a relation between said mutations and the evolution of our impressively big brains.

mouse copy

So what do you think? A useful label, or just another cheap can of condensed soup? Hopefully more to come on this in future months. Stay tuned!

2 responses to “Is Eukaryotic DNA Still Living in a Prokaryotic World? How Changing Our Labels Can Change the Way We Think about Genetics

  1. I think labels reveal a lot about our manner of looking at things and what they can reveal when examined carefully–which typically we don’t do unless we make a point of it–are often the unstated assumptions we make about the matters to which the labels are applied. So a lable can highlight one or more aspects of something even as it obscures other aspects.

    Try considering any commonly-used label for what it highlights and obscures and we begin to see examples of how labels shape our views and do this with extreme finesse so that in general we are hardly or not at all aware of the “shaping” that has occurred:
    In socilal and political affairs, the examples are easy to find:
    “illegal alien” ; “terrorist” ; “drop-out” ; “unwed-mother” ; prize-winning… (fill-in-the-blank) ; “modernized”, etc.

    I find “housekeeping” and “contingency” wonderfully interesting adjectives as applied to genes, don’t you? 🙂 Imagine if genes were aware of their human-lableled-status!

    “Hey, “housekeeper”, got a spill here.”
    “Yeah, I’m on it, “contingency” type.
    Huh?! Who you callin’ ‘contingency’?”
    Uh, I’m callin’ you ‘contingency’, pal. Ever counted how many times you been mutated? It ain’t even funny!
    “I’m adaptable, bud. Just remember that when some big scene-change happens and your mop-and-pail stuff don’t work no more, ‘kay?”

    By the way, I love the graphics. The “Contingency Genes” on a Campbell’s soup can label—that’s inspired. Your recent posts are ones I print and re-read because they’re worth the added attention and reflection on my part.

  2. So true about labels highlighting AND obscuring issues. Reminds me of my continued (yet slow) reading through Kuhn’s “The Structure of Scientific Revolutions” in which he talks about how paradigms refocus investigative/theoretical energies but are never ever 100% accurate in their predictions. –That’s the “obscuring” part.

    Btw, love the mock duologue. I can just picture my genes arguing amongst themselves, wrapped in heated debate about molecular theory or something. Or maybe just what clothes to wear, who knows.

    And thanks for the props on the pics. I was an artist before I was ever a scientist and, given time and energy constraints, have moved into photography as a sideline hobby. Hence, I’m very familiar with Photoshop, which comes in pretty handy for pics on the blog. (Hopefully Campbell or Coca Cola doesn’t come and demand I take down these pics. It’s all for science after all!)

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