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An apple a day…

Posted: March 16, 2011 in genetics, just for fun

It all began normally enough. I was wearily poking at the discarded remnants of a neglected portabella bin, wondering to myself if it was relevant to check whether mushrooms had gotten moldy, when from across the room I spied a soccer mom pick up the most amazing specimen ever to enter a grocer’s produce aisle…

I immediately sprang into action: illuminated by harsh fluorescent lights I raced across the scuffed linoleum floor, leaping over a power cord (what the heck was that doing there?!) as I dived headlong toward the unsuspecting woman holding this wondrous apple just so – such that I could see its glory while she merely thought it was red. Here’s a hint: The lady next to her, had she bothered to look, would have called the apple green.

Despite the utter lack of interest she had previously displayed toward her selection as she sifted through the bin of golden deliciousness, this unfortunate lady for a moment seemed to find offense to my apple-snatching tactics. I, however, had clearly won the grab and flaunted my remarkable trophy in the air with a triumphant “Yeeessssss!” Obviously well versed in fight picking and not-picking, my victim exhaled heavily, shrugged, and turned to resume her half-hearted fruit sorting.

Now what, you might ask, could make a biologist behave in such a manner at the neighborhood market? For what would she risk potential eye rolling, hip-jutting, over-exaggerated throat clearing, and finger pointing? Obviously outnumbered and outwitted in this rather non-diverse sea of tired, bitter middle class women, I can only surmise that my epinephrine pathway took control and caused an action response not entirely conscious.

And thank goodness it did, because otherwise I might have hesitated a moment too long and forever regretted my cowardice. You see, this apple was a genetic Golden Ticket. A needle in the proverbial haystack; and almost lost innocuously forever in a mouthful of hay by an unappreciative horse. Not that I’m comparing this lady to a horse, mind you.

I understand my enchanted apple to be a rare genetic anomaly. Or, as the last guy put it, “It’s a genuine one-off and none of us have ever seen an apple like it before.” Couldn’t have said it better myself.

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I adore apples. And I hate doctors. Like the chicken and the egg, however, I’m not sure which of those came first in my life… So let’s discuss the biology of apples a bit! But oh! where to begin? So much fascination and so little space! First of all, apples have the largest plant genome sequenced to date…or at least the apple TREE does, and specifically the Golden Delicious, which was singled out from over 7500 varieties to have its DNA code immortalized first. From that sequencing project, we have learned other interesting tidbits, such as that the wild Eve of apples (common ancestor, Malus sieversii) was born in the mountains of modern-day Kazakhstan and acquired its ginormous genome through at least one major duplication event (a large genome is thought to render competitive advantages and other major evolutionary implications – for example, vertebrates are throught to have arisen from a genome duplication in some shared invertebrate ancestor).

More on this topic later – I’ll share with you my, and biologists of various other specialties’ , suspicions regarding the specific source of this special apple’s phenotype. Here’s a hint for those of you extra-credit point seekers: What has the body of a lion, the head of a goat, a snake for a tail, and breathes fire?

You may have seen the title of this post and thought: “Oh! It’s like Jeopardy! And the question is…What three things are mutually exclusive?” I initially typed these words without irony, inspired into blogging action by the resignation of NPR CEO Vivian Schiller; however, this simple title took on new life as it glared back from the screen.

Whether you are conservative or liberal, work with your head or work with your hands, are with us or against us, look black or white or in between, a universally shared trait seems to be the inherent skepticism (no matter from whence it stems) of these three words thrown inexplicably together: Politics. Media. Truth. What has so united us in our distrust?

I’m reminded of something David Gergen alluded to while speaking at UTA’s Maverick Speaker Series last year: What we need (I believe he was initially making an inter-generational comparison, which I will here take the liberty of scaling up to the whole population level) is a cause for passion. Previously in this great nation of ours, we have been united by common goals that often included battles, whether of the physical or ideological nature. Importantly, these causes gave all Americans, regardless of background or affiliation, a united stance to take on a directed measure. The example Gergen used was the first two World Wars: These were just, he argued, and everyone agreed. What Gergen then called for, in an argument under-appreciated at best, is a new united front – a new reason to band together – and one that is nonviolent. Simply stated, we need to SHARE PASSION if we are to ever feel content. What, asks Gergen, since the Great Wars, have we ever ALL BELIEVED IN, all at the same time and in the same place? Give us a common cause, a good one, and you’ve just given us a clear path forward.

The question is, of course, rhetorical. And the history of human nature seems to suggest only great injustice can incite unified indignity. Unfortunately, I share the perspective of Einstein when it comes to the disturbing concept of raging a third world war: “I know not with what weapons World War Three will be fought, but World War Four will be fought with sticks and stones.”

Economics often serves to remind us biologists of just how animal-like humans truly are. All our supposed logic and reason and critical thought can be explained and predicated by laws that serve game theorists, behaviorists, ecologists, and evolutionists equally well.

This was the order of events:

  1. My estimable colleague Larry and I were immersed in one of our many interesting conversations when he mentioned his son’s former San Antonio apartment having a box on the wall. This box was approximately 80 years old. It took him a while to figure out what the box was.
  2. I reminisced about, then actually popped into the DVD player, Mary Poppins. Remember watching Mary Poppins as a kid? (You should, because you led a depraved childhood if not.)
  3. I witnessed that the old-fashioned telephone was in a box. Simultaneously, I observed the hand-crank powering it.
  4. This morning, Plinky delivered a “prompt” to my inbox: “Would you like to dance?” it asked.
  5. I figured I’d kinda like to dance. I also suddenly recalled reading about an off-the-grid dance club that powers itself by using the dance floor as a huge generator, channeling the dancers’ energy to create electricity.
  6. I thought to myself about how the hand-crank telephone concept had morphed and re-emerged on the dance floor…
  7. And wondered why we didn’t do this more often???

After looking into it, I discovered one can actually purchase exercise equipment, mostly of the stationary bike nature, capable of acting like generators, potentially powering the host gym directly, and also able to charge a battery of some sort.

Holy singing fish! I’d love to get in on that patent! Seriously, though, it is glaringly clear we became so over-indulged and deluded by convenience during the twentieth century that one of the simplest, most obvious and sustainable concepts was lost to us when it could best have been incorporated: Harnessing the energy we were already spending to power our machines. Novelty aside, this is a fantastic idea we should never have divorced ourselves from – especially not in favor of burning organic stuff at remote locations.Come on, America! Move it, grassroots-style! This is the best idea no one is talking about. Gyms, obviously, should be powered this way. But, duh, so should everything else! For people like me, who have trouble concentrating and hate sitting still for long periods of time, I KNOW my office productivity would be greatly enhanced if I had some pedals to push as I sat deskbound. (And my coworkers would probably appreciate a break from the pushing of their buttons…) It need not be a high-tech elliptical, or even that fancy a contraption at all: Just an inconspicuous under-the-desk foot crank would be fine. Moreover, I wouldn’t feel as great an urge to spend hours on the treadmill after work if I wasn’t merely plopped immobile on my rear all day. I foresee additional benefits as well, including a decline in irrelevant (and irreverent) daydreams, naps, and various other creative forms of procrastination.

If we’re fat because we don’t move enough, but our modern jobs and technology have left us with nowhere to go, why on this significantly-less-green-than-desirable planet would we keep on burning up our finite natural resources while wasting all that potential energy trapped in our expansive potbellies? We’d be happier, we’d be healthier; we and our Earth would live longer together.

Think about what the Wii has done for video games. Kids big and little have ventured forth from the comfort of the couch and discovered joy in motion. Why doesn’t the Wii power itself, I ask? Now take it one step further and imagine this: The television requiring power by movement at all times! Ah hah! Wanna watch Jersey Shore? Well then keep on pedaling cause the show stops when you stop! If we cannot separate ourselves from our modern toys, isn’t it at least ideal for them to require our work to work? Technology needn’t be effortless to be appreciable.

It is estimated an average person generates about 100 watts of power during an hour of sweating. A seasoned spinner might pump out 400 watts. Think about it.

Earth Day is approaching – April 22 – And this year it shares the calendar with Good Friday. For some this connection holds significance; for others, less so. Either way, this coincidence has led me to reflect upon the potential to unite unique (and often overlapping) groups of people for one crucial common cause.

I’d like your feedback on Earth Day Celebration ideas for our campus and community. Please share any thoughts, suggestions, or ideas you have to make our day memorable, and to initiate little changes toward making big differences. You can find some starting points here and here. In addition, I owe E.O. Wilson for the ideas below:

The human species has adapted physically and mentally to life on Earth and no place else. Ethics is the code of behavior we share on the basis of reason, law, honor, and an inborn sense of decency, even as some ascribe it to God’s will.

For some, the glory of an unseen divinity; for others, the glory of the universe revealed at last. For some, the belief in God made flesh to save mankind; for others, the belief in conscious free will. Some claim to have found a final truth; I am still searching. I may be wrong, you may be wrong. We may both be partly right.

Do our differences in worldview separate us in all things? They do not. You and I and every other human strive for the same imperatives of security, freedom of choice, personal dignity, and a cause larger than ourselves. Let us see then, if we can work together to solve a great problem. I suggest we set aside our differences to save The Creation. The defense of living Nature is a universal value. It does not rise from, nor does it promote, any ideological dogma. Rather, it serves without discrimination the interests of all humanity.

The Creation – living Nature as we know it – is changing rapidly and appears to be in distress. If the current extinction rate continues unabated, the most conservative estimates still calculate that the cost to humanity, in wealth, security, and quality of life, will be catastrophic. Whatever our background, surely we can agree that each species, however inconspicuous and humble it may seem, is a masterpiece of biology, of divinity. Each species possesses a unique combination of genetic traits that fits it more or less precisely to a particular part of the environment. Prudence alone dictates that we act quickly to prevent loss of biodiversity and, with it, the pauperization of our ecosystems – hence of The Creation.

You may well ask at this point, Why me? Because religion and science are the two most powerful forces in the world today; if they could be united on the common ground of biological conservation, many ecological problems (not to mention social issues!) would efficiently be addressed. If there is any moral precept shared by people of all beliefs, it is that we owe ourselves and future generations a beautiful, rich, and healthful environment.

The great challenge of the twenty-first century is to raise people everywhere to a decent standard of living while preserving as much of The Creation as possible. Science has provided this much: The more we learn about the biosphere, the more complex and beautiful it turns out to be. Knowledge of it is a magic well: the more you draw from it, the more there is to draw. Earth, and especially the razor-thin film of live enveloping it, is our home, our wellspring, our physical and much of our spiritual existence.

I know that environmentalism is linked in the minds of many with evolution, Darwin, and secularism. I don’t know exactly how or when or why this came to be. But I know the story of a young man, newly trained for the ministry, and so fixed in his faith that he referred all questions of morality to readings from scripture. When he first visited the Brazilian rainforests, he saw the manifest hand of God and in his notebook wrote, “It is not possible to give an adequate idea of the higher feelings of wonder, admiration, and devotion which fill and elevate the mind.”

That was Charles Darwin, as recorded in his personal journal in 1832 (now published as The Voyage of the Beagle).

Genesis 2:15
The LORD God took the man and put him in the Garden of Eden to work it and take care of it.

Islam is described in the Qur’an as the religion of nature. God declares: “Therefore, orient yourself, with all due sincerity and uprightness toward the natural religion; this is consistent with the nature He has created in humankind…this is the straight way. However, most of humanity realizes it not.” (30:30)

Cells Divide

Posted: February 27, 2011 in cell cycle, disorders, genetics

Here is a helpful study tool for the cell cycle: NOVA’s comparison of mitosis and meiosis

This is a great paper about cell cycle control – I also recommend you peruse PLoS regularly to find new, relevant information to help answer all your questions 🙂

Aberrant cell division is what we call cancer – cells that deny their place as a cooperative, sacrificial part of our body and instead replicate at our expense. All cancers are unique; additionally, it likely takes more than three independent events to give rise to a cancer cell. Thus, a “cure” for cancer is an ungrounded fantasy. However, there are two main characteristics that fundamentally link all cancers and their lack of cell cycle regulation: Lack of density-dependent inhibition and loss of anchorage control.

The initial discoveries of genetic alterations leading to cancer formation were gain-of-function mutations – these changes, creating mutant oncogenes, occur in normal cellular protooncogenes. The products of protooncogenes function in signal transduction pathways that promote cell proliferation. Studies suggest multiple, distinct pathways of genetic alteration lead to cancer, but that not all pathways have the same role in each cell type.

The significance of loss-of-function mutations has lately gained appreciation as well. The consequences of mutations in these tumor suppressor genes are not fully understood, though evidence suggests several encode proteins that prevent cell cycle progression through the division process. When functioning properly, tumor suppressor genes negate entry into or completion of the S, G2, or M phases. If protooncogenes are the accelerator when cells purposefully undergo division, tumor suppressor genes may be the brakes that halt them when growth is unnecessary.

So what does it means to “inherit” a predisposition to cancer? If cancer runs in your family, why might you be more likely to “get” it than others? Remember, now, that while you have a total of 46 chromosomes, your genome is in reality composed of two sets of 23 chromosomes. That is, you inherit one version of each chromosome from mom, and one from dad. These homologous chromosomes each hold the same genes in the same locations (termed loci) – but you may have gotten different versions – called gene variants or alleles – of these genes from each parent (and this still is only two of what may be hundreds of different versions available in our population’s collective gene pool). At any given loci (since we have ~20,000-25,000 genes, there are that number of loci in our genomes), you may have two different alleles; being a hybrid for any gene is termed heterozygous. Thus you potentially could inherit a faulty copy of the gene from one parent and a healthy copy from the other. Alternatively, you could have two healthy copies or two faulty copies – termed homozygous. How this affects you is largely speculation, though we can, in hindsight, observe trends and create percent likelihood values.

Tumor suppressor genes were initially recognized to have a major role in inherited cancer susceptibility. Because inactivation of both copies of a tumor suppressor gene is required for loss of function, individuals heterozygous  for mutations at the locus are phenotypically normal. Thus, unlike gain-of-function mutations, loss-of-function tumor suppressor mutations can be carried in the gene pool with no direct deleterious consequence. However, individuals heterozygous for tumor suppressor mutations are more likely to develop cancer, because only one mutational event is required to prevent synthesis of any functional gene product (Collins et al. 1997).

“Somewhere, in what had been up until then a near perfectly harmonious community of some one hundred trillion cells, a normal cell becomes a cancer cell. There is no sharp jab of pain to mark the event. There is no “festering” at the site of the transformation. There is no rallying of the immune system. The body accepts the cell as if it were one of its own (which it is), still under the control of the collective whole (which it is not).

For a long time, maybe twenty or thirty years, the cancer cell divides again and again. Even when its descendants number in the billions, the body exhibits no readily apparent sign or symptom of what has by then become a semi-independent mass with its own blood supply. By this time some tiny “gangs” of cancer cells have broken away from the original mass and have started thriving colonies in the brain and in the lungs, places to which the “colonists” were carried by the blood stream.

About the time the original mass reaches the ten-billion cell size, the body notices a lump.” From Dimensions of Cancer, by Charles E. Kupchella.

The Secret Recipe

Posted: February 26, 2011 in biochemistry, evolution, genetics

I am guilty, along with countless texts, websites, experts, and novices, of an academic travesty – using an inaccurate simile to explain scientific phenomena. Namely, the description of genomic information as a blueprint and the body as the resultant structure.

Thank goodness I recently failed to notice The Agile Gene was merely a renaming of Nature Via Nurture, and was therefore conned into reading it again. It reminded me of what I already knew, but lie buried beneath the weight of my formal education… Our DNA is not a blueprint but a recipe. We are not built, but baked.

The building designed from a blueprint is literally the sum of its parts. A cake, however, or a human, is a whole greater than its sum; it takes on properties not obvious from the list of ingredients. What, asks Blumberg in Body Heat, is the essence of a chocolate cake? Is it the eggs? Flour? Cocoa? No, these are merely ingredients. Nor is it the pan, oven, or whisk. A recipe is clearly not a cake, either. What is the essence of a human? How can it be captured?

The reality is that simply unraveling our DNA does not explain how it works, any more than knowing the alphabet helps you to read a book (with apologizes to Charles Arthur).

It seems we expect too much of our limited understanding of DNA, which derives from the metaphors we use about it. When we can only describe something indirectly, it may falsely acquire the expectations realistic of the associated analogy. We therefore look to genes to solve riddles, fix problems, and explain mysteries. However, we forget that it just isn’t so simple…

Consider what the greatly missed writer Douglas Adams pointed out – Imagine that you were trying to describe how to make a fruit cake by writing the blueprint: currant here, surrounded by certain amount of air-filled cake mixture, and then more currants. It would be hellish. So how do we make fruit cakes? Not by blueprint. We use recipes – mix these things together, bake at a particular temperature for so long, and voila: if you’ve got the components right, you’ll have currants distributed satisfactorily around your finished product.

Think about it: Bakers use, by and large, the same ingredients in many recipes to produce a wide variety of unique confections. The art of baking lies in the ratio of flour to sugar to eggs to salt, and such; not in using different ingredients for each different recipe. Can you predict the precise structure, placement of parts, consistency, etc. of the product just by looking at a recipe? Nope.

Likewise, many organisms share many genes, probably from a common ancestor. We change around the timing, intensity, and location of gene expression, throw in a few special touches, and viola! become unique individuals. But it isn’t just genes that make us who we are – environment clearly affects the expression of genes.

Okay, so you’ve made the cake batter or bread dough or what have you – now what? The oven condition and quality, local elevation, humidity, etc. all have significant impacts on the final product. Some cooks create masterpieces at low temperatures for a long time; others dazzle with short durations of high heat.

The secret ingredient we’re often missing when we describe our genes as a blueprint is quite possibly that elusive fourth dimension, forgotten usually by its continuous presence – time. You can break a structure back down into its constituent components; you cannot unbake a cake. Or a person.

One of my favorite analogies used by Ridley is: You and I and other animals share the genes necessary to make vertebrae. This neck sauce, as he calls it, is used to marinate giraffes for a much longer time during their development than us people; yet we too were briefly soaked in that sauce. Snakes are basted in the marinade during their entire development and thus end up with a neck the length of their body! But each of us express the same neck genes in our neck region; the difference is how long, and how much marinade we soaked in as we developed. You see, we were not assembled, we were concocted.

If something disrupts our proper development, or throws off the timing of gene expression, then that something has the potential to cause disorders and disabilities. We are the products of the conditions in which our genes are expressed; not only that, but the conditions we find ourselves in further influence future directions of gene expression.

As the psychologist Gary Marcus has pointed out in yet another attempt at an applicable analogy by which to understand something not quite understandable, genes function like IF-THEN lines of code in a computer program. The IF refers to the regulatory portion of the gene and THEN refers to the protein template region.