Archive for the ‘genetics’ Category

Apple of My Eye

Posted: March 29, 2011 in evolution, genetics, just for fun, plants

Next time you bite into a sweet, juicy piece of fruit, don’t let your enjoyment be diminished by the realization that you are both eating an ovary and being manipulated into playing an active role in plant sex. Ignorance might seem like bliss, but really; that plump, fleshy goodness is just as satisfying nonetheless. Kind of. Mostly. But many plants NEED animals to help them with both copulation and then also distribution of offspring, because plants can’t just get up and walk to the singles bar, nor can their children move away. So these chlorophyll-laden Casanovas devised tactics to entice unsuspecting motile creatures to do their dirty work for them. In exchange for a little sugar high, plants romance animals into carrying off feats of reproduction and migration without so much as ruffling a leaf.

Angiosperms, or flowering plants, began to dominate the planet (taking over from the Gymnosperms, which bear “naked” seeds) as insects also began to radiate into incredible abundance, diversity, and ubiquity. Coincidence, you might ask? Not so fast – with flying pollinators unabashedly doing the deed for immobile plants, these clever vegetables developed all sorts of sneaky tricks to entice the growing insect population to carry their sperm for impregnation of ova far and wide. This co-evolution gives us both the diverse beauty of the plant kingdom and the specific flower (sight, taste, smell) preferences of the animal kingdom.

I think now is a good time to discuss the difference between a fruit and a vegetable… So: All a plant’s somatic, or non-reproductive cells, make up vegetative structures. Why do we (perhaps unkindly) refer to comatose patients as existing in a “vegetative” state? Well, they’re not moving, they’re not reproducing; in fact, they are rather plant-like! On the other hand, certain structures may become specialized for reproduction – in plants, cells dedicate themselves to one or the other: normal body growth and development, OR reproduction. Flowers and their resulting fruit are such specialized tissues. Thus, any plant part NOT involved in reproduction (i.e. vegetative) is called a vegetable, while those parts directly involved in sex are called fruit. You can distinguish this by determining whether a piece of produce has seeds, which are plant embryos. Sans seeds, you have some vegetative structure from the plant. Squash? Fruit. Peppers? Fruit. Nuts? Fruit. Avocado? Fruit. Olives? Fruit. You see where I’m going with this. Seeds = Fruit. Beans and peas ARE the seeds! (The pod is the fruit.) This defies the conventional wisdom of amateur chefs around the globe. Consistently, we call items traditionally seasoned with savory flavors “vegetables” while reserving “fruit” for items incorporated in sweet dishes. You may want to take a moment to reflect and recoup after that reality-altering realization.

When it’s time for an angiosperm to have sex, the plant diverts energy and nutrients into creating differentiated reproductive structures. Leaf and other tissues specialize into distinct flower components by altering gene expression and up-regulating exactly those genes necessary for each cell’s particular role. A flower often has female parts – collectively called the carpel, and male parts – comprising the stamen. On the anthers (tips) of the stamen, pollen grains are hollow structures housing millions of individual male gametes (sperm!). Insects pick up these grains and transport them to the carpel of a different plant. Flowers, then, share a bit of nectar in exchange for fertilization!You know that bulbous structure at the base of flowers? Within that ovary lies the ova, or eggs, of the flower. When a bee brings foreign sperm into contact with a viable egg, the receptive flower begins to produce ethylene gas, which triggers the decline of any flower parts not essential in seed and fruit formation (this is the same compound that causes ripening of fruit). Simultaneously, the receptacle and/or ovary wall tissue grows, swelling in size to form a protective (and often tasty!) structure in which to house the developing offspring. Eventually, the structure begins to look like a fruit as we know it; the seeds are the embryos (or house the embryos).

When trees establish themselves in the ground, they compete with one another for resources; access to sunlight, and surface area to absorb water and nutrients from the soil. Mature trees then will often be found spaced apart, at whatever distance that particular ecosystem has the nutrients to support them. So to prevent the parent tree from competing for valuable resources with offspring, trees would like to be able to distance themselves from their seedlings…..And so: The fruit was born. When you or I or some other creature comes along and spies a shiny treat dangling tantalizingly from the tree, we promptly grab it and go. In doing so, we are feeding right in to the plant’s plot – As we wolf down the sweet snack we inadvertently consume the seeds (or, for picky humans, toss them far from the parent plant). Fruit, then, share a bit of nutrition in exchange for seed dispersal (where do you think the term “spreading his seeds” comes from?!).

Intact seeds pass through our digestive system without great harm to the protected embryo. It’s no coincidence that fruits contain fiber and other compounds that aid in excretion; in fact, many fruits contain natural laxatives that induce peristalsis (smooth muscle contraction in your digestive tract) and literally force expulsion of the seedlings. This is pure plant genius. Not only have you safely carried (dispersed) the angiosperm offspring to a new location, you have planted it happily within a cushy pile of fresh, hydrated fertilizer. What more could a germinating baby plant ask for??

Incidentally, it isn’t only plants who have evolved these sneaky tactics – fungi do their fair share of animal manipulation as well. After all, what is the stereotypical place to find ‘shrooms? All’s fair in love and war. And love is war.

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?

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.

One Gene = One Protein

Posted: February 12, 2011 in biochemistry, genetics

Once upon a time, every organism was a single cell. Whether the product of binary fission, mitosis, or sexual fertilization, all of life’s secrets are held in a microscopic unit with an average (eukaryotic) diameter of 0.00001 meters.

What the components of any given cell are, whether it contains organelles, and which, and a number of other variables are dynamic between creatures and over time. The one thing all cells have, however, that defines them as living organisms, is heritable information – nucleic acids – and the machinery required to process those directions – ribosomes.

When our DNA directs growth and development, and provides the defining characteristics of our selves, what really is happening? How can a four-letter sequence of sugar-phosphate-nitrogenous bases create a living being? And then, in the case of multicellular organisms, build it up to a coordinated, functioning whole?

Excepting our red blood cells, all our somatic (body) cells contain our entire genome. The only difference between cells in different parts of your body is WHICH genes are turned on, to what degree (level) each is expressed, and when. In addition, the genes you turn on and off even within distinct body regions are dynamic over time – coordinating the correct set of genes is essential for proper development, proportional body growth, to maintain homeostasis in an ever-changing environment, and to regulate life cycles.

What does it mean to say that a gene is expressed? Less than 2% of our entire genome actually consists of “genes” – these are the stretches of nucleic acid “words” that encode instructions for the creation of a specific protein. Proteins themselves are composed of amino acids – your DNA is read as three-letter words; each triplet of bases, termed a codon, specifies one particular amino acid equivalent. If you had a random collection of objects from which to choose, you might say “hat” – and could then also select the literal item itself. You could then perhaps say “bat,” and so on. Your DNA gene would be the complete list of three-letter codon words like “hat”  and “bat,” and the piece of the protein it referred to (individual amino acids) would be the objects we named a hat and bat and etcetera. A gene, then, is a stretch of DNA that refers to an actual object; genes are said to be expressed when that gene is read as directions and the object, a protein, is assembled within your cells. When all these components have been properly created and distributed, you might have a full game of baseball, or a functional organism.

To protect that most precious of all molecules, DNA, your cells enclose it in a membrane-bound nucleus. When a particular gene needs to be expressed, that specific DNA region is copied into an RNA transcript. This RNA copy of the DNA gene is then exported from the nucleus to the cytoplasm, where expression is completed. The process of creating an RNA copy of a single gene from the DNA template is called transcription; just as the general definition of the term would imply, this process involves making a same-language copy of the DNA words. The alphabet looks nearly the same (the letters are G, C, A, and U – where U is substituted for the T of DNA); you can think of RNA as a different dialect, or accent, of the language of DNA.

The RNA transcript of a demanded gene is now greatly shorter, and therefore easier to work with, than the original full DNA genome. This sequence may be further processed before the act of translation occurs in the cytoplasm. During translation, the RNA triplet codons of nucleic acids are exchanged for the associated amino acid in a growing peptide chain. In other words, just as with the general definition of “translation,” one language is changed into another – but while retaining the original meaning. As the polypeptide grows, it is folded and processed and eventually emerges as a functional protein. At this point, your original DNA gene has been expressed.

All of your characteristics are the result of protein creation during gene expression. Your eye color is the accumulation of proteins that reflect certain wavelengths of light back to the eyes of others (if you have green eyes, or brown eyes, or hazel eyes, it’s because the protein pigmentation in your eyes does NOT absorb that particular color and shade, reflecting it for others to see). Likewise for your hair color and skin color, and all color! All of these phenotypic traits are coded for by not one, but a complex combination of genes. Not only do individual genes and proteins make you who you are, but the interactions between multiple genes and proteins also contributes to your unique self.

“There is grandeur in this view of life, with its several powers, having been originally breathed by The Creator into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.”

(Last paragraph from Darwin’s The Origin of Species)

Incidentally, ladies and gentlemen, today, 12 February is International Darwin Day.

Photo 51

Posted: February 12, 2011 in biochemistry, genetics

How does DNA work? How can something so seemingly arbitrary – something composed of four bases each containing simply a sugar, a phosphate group, and a nitrogen-containing compound – determine our appearance, instincts, thoughts, behaviors, and very existence?

Humans have 46 chromosomes, or 23 paired sets (one each from ma and from pa!). Altogether, the human genome has roughly 3 billion base pairs – in other words, the genetic information directing our lives is a “book” containing 3 billion “letters.” If you were to stretch it all out end-to-end, you would discover yourself to be carrying about 6 feet of DNA per cell, or 2 billion miles of genetic information total. Wow! The alphabet itself contains only four letters; most of the words are the same for each of us (think: if they weren’t, you might have limbs or organs in different places than the guy next to you!), but the difference between any two humans can reach up to 0.1% (this may seem like a small number, but it is still about 3 million letters). Most of the differences, called single nucleotide polymorphisms, are singular and located in isolated spots rather than in full “words” or long stretches.

Journey Into DNA

Humans have an estimated 20,000-25,000 genes. These “words” – the part of your DNA that is coded into protein – make up only about 1.5% of your total genome! What does the rest do? Well, that question is a work still in progress:

How do we know what DNA looks like? How do we explore our genes at the molecular level? In biochemistry, form and function go together like peanut butter and bananas (trust me, it’s good). Most of our knowledge comes from analyzing data garnered during elegantly designed, indirect experiments. Today, we often use highly sophisticated computer programs to discern the secrets of our genes, but originally we relied heavily on X-ray diffraction.

From this image, taken by Rosalind Franklin in 1952, did modern genomics emerge:

The Anatomy of Photo 51