DNA Expression

In this class, we will not dive into the nitty-gritty of DNA structure. If you find that interesting, I highly recommend you take an introductory Biology class, and/or Anthropological Genetics. This semester, we are focusing on human traits, variation in those traits among modern people, and how those traits vary over time and in closely related species. To understand this "big picture" view of human genetics, there is one important thing you need to know about DNA: it is flexible.

Genes, you'll recall, code for a string of amino acids that make up a protein. A gene is more-or-less "locked in" to the protein it creates. It's string of DNA codes for a specific sequence of amino acids, so it can't "decide" to create a completely unrelated protein. That said, whether or not a gene is expressed (that is, actually creates a protein and the effects of that protein) and how it is expressed (the specific proteins created) are flexible. DNA responds to environmental cues that determine whether or not a protein is created at all, and, in some cases, which of several closely-related proteins are made during the process of expressing a gene.

Turning genes on and off

It's easiest to see the flexibility in our genes when we recognize that not all genes are expressed (make their protein) in all times and places. For example, globin is a protein that allows red blood cells to carry oxygen through your body. The genes for making globin must be "turned on" in the cells that create red blood cells. But, most of the cells in your body do not create red blood cells. Almost all of the cells in your body have a full set of your DNA, but the cells of your skin, pancreas, or intestine don't make globin. In those cells, a chemical block (a mechanism called DNA methylation), prevents the gene that codes for globin from ever being expressed.

Even when a cell does produce a particular protein, it often only does so if there is an environmental stimulus that triggers it. For example, we all have hormone cycles. Too much of one hormone creates an environment that signals to cells they should stop producing it. Too little can send the opposite signal. Sometimes, the presence of one hormone creates the correct environment to trigger the production of another. For example, when an egg is fertilized by sperm, creating an early pregnancy, the fertilized egg gives off the hormone hCG (human chorionic gonadotropin), which a woman's body does not create on its own. The presence of hCG triggers the production of estrogen and progesterone, which cause the woman's body to retain her uterine lining (which would usually be lost during her period), and therefore maintain the pregnancy.

Flexibility in protein creation

Although the DNA strand that makes up a gene is the same throughout your life, it does not always create the same protein every time it is "turned on". For example, one gene codes for calcitonin, a hormone produced in the thyroid and pituitary gland. The same gene creates CGRP (calcitonin-gene-related peptide), a separate -- albeit related -- protein. Whether the gene codes for calcitonin or CGRP depends on how the DNA strand gets turned into a string of amino acids.

The initial step in creating a protein from a gene is call transcription. During transcription, the double helix of the DNA strand pulls apart, allowing RNA molecules to make a mirror image of a gene. The RNA copies (transcribes) the entire DNA sequence. But, that sequence includes both exons (segments that code for useful strings of amino acids, the portions that will make up an eventual protein) and introns ("intrusive" segments that are mostly "junk DNA", they do not produce a string of amino acids that could be usefully turned into a protein.) Most of our DNA is actually non-coding.

During the first step of transcription, RNA copies both the exons and introns. After the RNA has finished creating a mirror of the DNA strand, however, it breaks away, allowing the DNA double helix to bind itself back together. The RNA then excises the introns and splices the exons together in a coherent way. To use a language metaphor, perhaps the original RNA strand looked something like this, where the red letters represent exons, and the green ones introns:

Now;awoiuisouaprug'fjtheklfjadswinterw;iru twpoiaghoffoiuj''erpour;qoir.hkjdiscontenta'so;lkf

After this RNA strand broke away from the DNA, the introns and exons would be cut apart:

Now ;awoiu is ouaprug'fj the klfjads winter w;iru twpoiagh of foiuj''erp our ;qoir.hkj discontent a'so;lkf

Next, the introns would be excised:

Now ;awoiu is ouaprug'fj the klfjads winter w;iru twpoiagh of foiuj''erp our ;qoir.hkj discontent a'so;lkf

Finally, the exons would be spliced back together, with the introns removed:

Now_is_the_winter_of_our_discontent

Only after the "sentence" made by the RNA strand is correct does the strand leave the nucleus of the cell and bind with amino acids to create a protein. This process of putting amino acids into the correct sequence is called translation.

In the case of calcitonin and CGRP, there is more than one "sentence" that can be made by the original DNA strand. To extend our metaphor from above, imagine that, again the original RNA strand looked like this:

Now;awoiuisouaprug'fjtheklfjadswinterw;iru twpoiaghoffoiuj''erpour;qoir.hkjdiscontenta'so;lkf

This time, however, when the introns are excised, a different set of exons is included:

Now ;awoiu is ouaprug'fj the klfjads winter w;iru twpoiagh of foiuj''erp our;qoir.hkj discontent a'so;lkf

This creates a completely different sentence from the same original gene:

Now_is_winter

Which "sentence" or protein is created depends on the environmental triggers that cause the gene to be "turned on" in the first place.

This flexibility is whether and how proteins are created from genes is why I referred to our DNA as our body's owner's manual, rather than a blueprint. Blueprints lay out a rigid structure that must be followed or nothing that comes later will properly function. Although, obviously, we need certain basic functions to live, our DNA is not that rigid. Instead, our genes react to environmental stimuli, "looking up" possible responses in our owner's manual, depending on what light turned on on the dashboard.