Basic Genetic Mechanisms - Mutation & Disease

Mutation____________________________________________________

A mutation is a change in the DNA of an organism. Most mutations are harmful, but because of the redundancy of DNA (that certain codes are repeated over and over), a mutation in a single area may have only a minimal effect.

A mutation is a change in the nucleotide sequence of a short region of a genome. Many mutations are point mutations that replace one nucleotide with another; others involve insertion or deletion of one or a few nucleotides. Mutations result either from errors in DNA replication or from the damaging effects of mutagens, such as chemicals and radiation, which react with DNA and change the structures of individual nucleotides. All cells possess DNA-repair enzymes that attempt to minimize the number of mutations that occur. These enzymes work in two ways. Some are pre-replicative and search the DNA for nucleotides with unusual structures, these being replaced before replication occurs; others are post-replicative and check newly synthesized DNA for errors, correcting any errors that they find. A possible definition of mutation is therefore a deficiency in DNA repair.

A point mutation is very easy to understand. It simply means that one base is replaced with another. For example, if a part of the DNA should read TAC GGA ACT ATG but instead reads TAC GCA ATT ATG, then a point mutation has occurred in the third codon. Notice that all of the other codons remained the same. So if this part of the DNA were transcribed into mRNA which was later translated into a protein molecule, only one amino acid would be different than usual since only one codon was changed. Usually, a protein with only one amino acid different can still function normally.

By contrast to this minor effect, frame shift mutations can have much more serious consequences. A frame shift mutation occurs when a base is either added or deleted from the DNA sequence. Taking the example from before, suppose that a nucleotide with thymine was added in the second codon so that the sequence becomes TAC GGCA ACT ATG. Since the codons are triplets, this would actually be read as TAC GGC AAC TAT G... The first codon is the same, but all of the other ones are completely different, so the protein produced would also be very different from what it should be. Usually, the resulting protein will not be able to perform the function that the original one was meant to do. This is why frame shift mutations have far more severe effects than do point mutations.

Changes to individual bases______________________________________

Remember that a set of three bases in a gene in DNA codes for a particular amino acid. If you have followed this sequence of pages from the beginning, you will have come across this table showing the codons in DNA:

A gene will be made up of a string of these codes rather like a string of 3-letter words in a sentence. We'll use that as a simple analogy. Take the sentence:

the big fox bit the dog but not the boy

Suppose one letter got changed in this by accident. Suppose, for example, the "d" in dog got replaced by a "p". The sentence would now read:

the big fox bit the pog but not the boy

Clearly this doesn't make complete sense any more. Would that matter if the same thing happened in a gene? It depends!

If you look back at the table, there are several amino acids which are coded for by more than one base combination. For example, glycine (Gly) is coded for by GGT, GGC, GGA and GGG. It doesn't matter what the last base is - you would get glycine whatever base followed the initial GG.

That means that a mutation at the end of a codon like this wouldn't make any difference to the protein chain which would eventually form. These are known as silent mutations.

Alternatively, of course, you could well get a code for a different amino acid or even a stop codon. If a stop codon was produced in the middle of the gene, then the protein formed would be too short, and almost certainly wouldn't function properly.

If a different amino acid was produced, how much it mattered would depend on whereabouts it was in the protein chain. If it was near the active site of an enzyme, for example, it might stop the enzyme from working entirely.

On the other hand, if it was on the outside of an enzyme, and didn't affect the way the protein chain folded, it might not matter at all.

Inserting or deleting bases_______________________________________

The situation is more dramatic if extra bases are inserted into the code, or some bases are deleted from the code. Using our example sentence from above, and keeping the three letter word structure:
 
If you insert a single extra base:

the big fro xbi tth edo gbu tno tth ebo y

An extra "r" is inserted in "fox". If the sentence still has to be read three letters at a time (as in DNA), everything from then on becomes completely meaningless.

If you delete a single base:

the big fxb itt hed ogb utn ott heb oy

This time the "o" in "fox" has been deleted. And again, because we have to read the letters in groups of three, the rest of the sentence becomes completely wrecked.
So does this matter? Well, of course it does! Large chunks of the protein will consist of completely wrong amino acid residues.

We've looked so far at inserting or deleting one base. What if you do it for more than one?
The effect is the same unless you add or delete multiples of three bases - without changing any other codons. If you added an extra three bases between two existing codons, then essentially you are just adding an extra word.

the big fox bit the xjy dog but not the boy

That extra word represents an extra codon in the DNA, and so an extra amino acid residue in the protein chain. Does this matter? It depends where it is in the chain (Is it important to the active site of an enzyme, for example?), and whether it affects the folding of the chain.

What if the three bases were inserted so that they broke up an existing codon? Here is the same extra "word", "xjy", dropped in the word "bit". Everything is then reshuffled into groups of three letters.

the big fox bxj yit the dog but not the boy

You can see that the effect is again fairly limited. It will change one codon completely, and introduce an extra codon. That would give you one different amino acid and one extra amino acid in the chain. Again, how much that would affect the final protein depends on where it happens in the chain.

Deleting a whole codon again leaves most of the protein chain unchanged. Again, whether the function of the protein is affected depends on where the missing amino acid should have been and how critical it was to the way the protein folded.





Some diseases caused by mutation_________________________________
 
The following examples illustrate some of the changes we've looked at above and how they can result in disease.

Cystic fibrosis
Cystic fibrosis is an inherited disease which affects the lungs and digestive system. It results from mutation in a gene responsible for making a protein which is involved in the transport of ions across cell boundaries.
The effect is to produce a sticky mucus which clogs the lungs and can lead to serious infection. A similar sticky mucus also blocks the pancreas (a part of the digestive system) which provides enzymes for breaking down food. This gets in the way of the processes which convert the food into molecules which can be absorbed by the body.

There are lots of different mutations which can cause this, but we'll just have a quick look at the one which accounts for about 70% of cystic fibrosis cases.

The base sequence in the part of the gene affected ought to look like this:

 
The phenylalanine (Phe) in red is the amino acid which is missing from the final protein in many sufferers from cystic fibrosis. However, it isn't quite as simple as just losing the TTT codon.
 
Instead, the three bases lost are:

That leaves the sequence:

Notice that the amino acid sequence is identical to before but without the phenylalanine. How did that happen when we didn't actually remove the whole of the phenylalanine codon?
If you look carefully, you will see that the codon for the second isoleucine (Ile) is different from before. It so happens that isoleucine is coded for by both ATC and ATT. Once the second T (the red one) has joined the existing AT, all the rest of the base sequence is exactly what it was before.

Sickle cell anaemia    

This is so called because red blood cells change their shape from the normal flexible doughnut shape to a much more rigid sickle shape - rather like a crescent moon.

It results from the change of a single base in a gene responsible for making one of the protein chains which makes up haemoglobin.

The affected part of the gene should read:

What it actually reads in someone suffering from sickle cell anaemia is:

The effect of this single change is to make the haemoglobin temporarily polymerise to make fibres after it has released the oxygen that it carries around the body. This changes the shape of the red blood cells so that they don't flow so easily - it makes them sticky, especially in small blood vessels. This can cause pain and lead to organ damage.

 

Genetic diseases associated with defects in DNA repair systems.

Bioenergetics & Metabolism

Mitochondria: Cellular Power Plants

Blink. Breathe. Wiggle your toes. These subtle movements—as well as the many chemical reactions that take place inside organelles—require vast amounts of cellular energy. The main energy source in your body is a small molecule called ATP, for adenosine triphosphate.

ATP is made in organelles called mitochondria. Let's see if we can find some. They look like blimps about as long as pickup trucks but somewhat narrower. Oh, a few of them are over there. As we get nearer, you may hear a low whirring or humming sound, similar to that made by a power station. It's no coincidence. Just as power plants convert energy from fossil fuels or hydroelectric dams into electricity, mitochondria convert energy from your food into ATP.

Like all other organelles, mitochondria are encased in an outer membrane. But they also have an inner membrane. Remarkably, this inner membrane is four or five times larger than the outer membrane. So, to fit inside the organelle, it doubles over in many places, extending long, fingerlike folds into the center of the organelle. These folds serve an important function: They dramatically increase the surface area available to the cell machinery that makes ATP. In other words, they vastly increase the ATP-production capacity of mitochondria.

The mazelike space inside mitochondria is filled with a strong brew of hundreds of enzymes, DNA (mitochondria are the only organelles to have their own genetic material), special mitochondrial ribosomes, and other molecules necessary to turn on mitochondrial genes.

	ACTUAL SIZE (AVERAGE)	PERCEIVED SIZE WHEN MAGNIFIED 3 MILLION TIMES
Cell diameter	30 micrometers*	300 feet
Nucleus diameter	5 micrometers	50 feet
Mitochondrion length	Typically 1–2 micrometers, but can be up to 7 micrometers long	18 feet
Lysosome diameter	50–3,000 nanometers*	5 inches to 30 feet
Ribosome diameter	20–30 nanometers	2–3 inches
Microtubule width	25 nanometers	3 inches
Intermediate filament width	10 nanometers	1.2 inches
Actin filament width	5–9 nanometers	0.5–1 inch

*A micrometer is one millionth (10^-6) of a meter. A nanometer is one billionth (10^-9) of a meter.

Got Energy?

Energy from the food you eat is converted in mitochondria into ATP. Cells use ATP to power their chemical reactions. For example, muscle cells convert ATP energy into physical work, allowing you to lift weights, jog, or simply move your eyeballs from side to side.

The largest human cell (by volume) is the egg. Human eggs are 150 micrometers in diameter and you can just barely see one with a naked eye. In comparison, consider the eggs of chickens...or ostriches!

When you think about food, protein, and energy, what may come to mind is the quick meal you squeeze in before racing off to your next activity. But while you move on, your cells are transforming the food into fuel (ATP in this case) for energy and growth.

As your digestive system works on an apple or a turkey sandwich, it breaks the food down into different parts, including molecules of a sugar called glucose. Through a series of chemical reactions, mitochondria transfer energy in conveniently sized packets from glucose into ATP. All that's left are carbon dioxide and water, which are discarded as wastes.

This process is extremely efficient. Cells convert nearly 50 percent of the energy stored in glucose into ATP. The remaining energy is released and used to keep our bodies warm. In contrast, a typical car converts no more than 20 percent of its fuel energy into useful work.

Your body uses ATP by breaking it apart. ATP stores energy in its chemical bonds. When one of these bonds is broken, loosing a chemical group called a phosphate, energy is released.

ATP is plentifully produced and used in virtually every type of cell. A typical cell contains about 1 billion molecules of ATP at any given time. In many cells, all of this ATP is used up and replaced every 1 to 2 minutes!

Peter Mitchell, a British scientist, proposed the theory of chemiosmosis in 1961 to describe the way in which ATP is actually synthesized; he received the Nobel Prize for his work in 1978. In prokaryotes, it occurs at the cell membrane. In eukaryotic animal cells, chemiosmosis takes place in the cristae of the mitochondria, and in autotrophic cells, it occurs across the thylakoid membranes in the chloroplasts. Since chemiosmosis is the same for all three membranes, in the following discussion we will not need to differentiate between the membranes.

On one side of the membrane (we will call this side the "inside") is a supply of hydrogen atoms. Special carrier molecules use the energy released in the electron transport chain to bring hydrogen atoms close to the membrane and separate the hydrogen into an H+ ions and electrons. The electrons are brought back to the inside of the membrane while the H+ ions are forced to the other side (the "outside"). As more and more H+ ions accumulate on the outside of the membrane, two gradients are formed. First, a pH gradient is formed. This means that the outside is more acidic (because it has H+ ions) than the inside of the membrane. Also, an electrical gradient forms, since H+ ions have a positive charge.

When these gradients become sufficiently intense, they force the H+ ions through a channel (sometimes called the F₀ channel) in the membrane in a tremendous gush. The ions end up in a large structure called the F₁ unit where an enzyme called ATP synthetase is located. Also present in the F₁ are ADP molecules and phosphate molecules. As the H+ ions rush by, they provide the energy which brings the ATP synthetase, ADP, and phosphates together. The ATP synthetase bonds the ADP and phosphate molecules, forming ATP. The H+ ions, now on the inside of the membrane, can be transported by the carrier molecules across the membrane so that the process may be repeated when enough energy is released from the electron transport chain.

Plastids

Plastids are organelles which are found only in autotrophic cells. In many respects, plastids are similar to entire prokaryotic organisms; they contain their own DNA and can replicate themselves. Like the mitochondria, plastids have an outer membrane which separates them from the cytoplasm and a highly folded inner membrane. Plastids come in three different types: leucoplasts, chloroplasts, and chromoplasts.

 

Leucoplasts are colorless plastids which store starch (a carbohydrate), proteins, and lipids. These materials are released from the leucoplast when the cell requires them.

 

Chloroplasts are the organelles in which photosynthesis takes place. Photosynthesis is an important process by which autotrophic cells manufacture their own food. Chloroplasts contain the green pigment chlorophyll (this is why plant leaves are green) which absorbs light to provide the energy necessary to complete photosynthesis.

A chloroplast (image courtesy of Nanoworld)

Chloroplasts have two membranes: an outer membrane and an inner membrane. A solution called the stroma fills the part of the chloroplast inside of the inner membrane. In this area, there are stacks of flattened vesicles. The stacks themselves are known as grana, and the vesicles are called thylakoids. The thylakoids are where photosynthesis actually occurs.

 

Chromoplasts are very similar to chloroplasts, but they do not contain the green pigment chlorophyll. Instead, they contain other pigments which give color to flowers and to leaves during the fall. These other pigments absorb colors of light than chlorophyll.

Organelles

Overview

 

Welcome! I hope the transformation wasn't too alarming. You have shrunk down to about 3 millionths of your normal size. You are now about 0.5 micrometers tall (a micrometer is 1/1000 of a millimeter). But don't worry, you'll return to your normal size before you finish this chapter.

At this scale, a medium-sized human cell looks as long, high, and wide as a football field. But from where we are, you can't see nearly that far. Clogging your view is a rich stew of molecules, fibers, and various cell structures called organelles. Like the internal organs in your body, organelles in the cell each have a unique biological role to play.

Now that your eyes have adjusted to the darkness, let's explore, first-hand and up close, the amazing world inside a cell.

A typical animal cell, sliced open to reveal cross-sections of organelles.

Nucleus: The Cell's Brain

Look down. Notice the slight curve? You're standing on a somewhat spherical structure about 50 feet in diameter. It's the nucleus—basically the cell's brain.

The nucleus is the most prominent organelle and can occupy up to 10 percent of the space inside a cell. It contains the equivalent of the cell's gray matter—its genetic material, or DNA. In the form of genes, each with a host of helper molecules, DNA determines the cell's identity, masterminds its activities, and is the official cookbook for the body's proteins.

Go ahead—jump. It's a bit springy, isn't it? That's because the nucleus is surrounded by two pliable membranes, together known as the nuclear envelope. Normally, the nuclear envelope is pockmarked with octagonal pits about an inch across (at this scale) and hemmed in by raised sides. These nuclear pores allow chemical messages to exit and enter the nucleus. But we've cleared the nuclear pores off this area of the nucleus so you don't sprain an ankle on one.

If you exclude the nucleus, the rest of the cell's innards are known as the cytoplasm. Virtually all forms of life fall into one of two categories: eukaryotes or prokaryotes.

Eukaryotic Cells	Prokaryotic Cells
The cells of “complex” organisms, including all plants and animals	“Simple” organisms, including bacteria and blue-green algae
Contain a nucleus and many other organelles, each surrounded by a membrane (the nucleus and mitochondrion have two membranes)	Lack a nucleus and other membrane-encased organelles
Can specialize for certain functions, such as absorbing nutrients from food or transmitting nerve impulses; groups cells can form large, multicellular organs and organisms	Usually exist as single, virtually identical cells
Most animal cells are 10–30 micrometers across, and most plant cells are 10–100 micrometers across	Most are 1–10 micrometers across

Endoplasmic Reticulum: Protein Clothier and Lipid Factory

If you peer over the side of the nucleus, you'll notice groups of enormous, interconnected sacs snuggling close by. Each sac is only a few inches across but can extend to lengths of 100 feet or more. This network of sacs, the endoplasmic reticulum (ER), often makes up more than 10 percent of a cell's total volume.

 

The endoplasmic reticulum comes in two types: Rough ER is covered with ribosomes and prepares newly made proteins; smooth ER specializes in making lipids and breaking down toxic molecules.

Take a closer look, and you'll see that the sacs are covered with bumps about 2 inches wide. Those bumps, called ribosomes, are sophisticated molecular machines made up of more than 70 proteins and 4 strands of RNA, a chemical relative of DNA. Ribosomes have a critical job: assembling all the cell's proteins. Without ribosomes, life as we know it would cease to exist.

To make a protein, ribosomes weld together chemical building blocks one by one. As naked, infant protein chains begin to curl out of ribosomes, they thread directly into the ER. There, hard-working enzymes clothe them with specialized strands of sugars.

Now, climb off the nucleus and out onto the ER. As you venture farther from the nucleus, you'll notice the ribosomes start to thin out. Be careful! Those ribosomes serve as nice hand- and footholds now. But as they become scarce or disappear, you could slide into the smooth ER, unable to climb out.

In addition to having few or no ribosomes, the smooth ER has a different shape and function than the ribosome-studded rough ER. A labyrinth of branched tubules, the smooth ER specializes in synthesizing lipids and also contains enzymes that break down harmful substances. Most cell types have very little smooth ER, but some cells—like those in the liver, which are responsible for neutralizing toxins—contain lots of it.

Next, look out into the cytosol. Do you see some free-floating ribosomes? The proteins made on those ribosomes stay in the cytosol. In contrast, proteins made on the rough ER's ribosomes end up in other organelles or are sent out of the cell to function elsewhere in the body. A few examples of proteins that leave the cell (called secreted proteins) are antibodies, insulin, digestive enzymes, and many hormones.

Golgi: Finishing, Packaging, and Mailing Centers

Now, let's slog through the cytosol a bit. Notice that stack of a half dozen flattened balloons, each a few inches across and about 2 feet long? That's the Golgi complex, also called the Golgi apparatus or, simply, the Golgi. Like an upscale gift shop that monograms, wraps, and mails its merchandise, the Golgi receives newly made proteins and lipids from the ER, puts the finishing touches on them, addresses them, and sends them to their final destinations. One of the places these molecules can end up is in lysosomes.

Lysosomes: Recycling Centers and Garbage Trucks

See that bubble about 10 feet across? That's a lysosome. Let's go—I think you'll like this. Perhaps even more than other organelles, lysosomes can vary widely in size—from 5 inches to 30 feet across.

Go ahead, put your ear next to it. Hear the sizzling and gurgling? That's the sound of powerful enzymes and acids chewing to bits anything that ends up inside.

But materials aren't just melted into oblivion in the lysosome. Instead, they are precisely chipped into their component parts, almost all of which the cell recycles as nutrients or building blocks. Lysosomes also act as cellular garbage trucks, hauling away unusable waste and dumping it outside the cell. From there, the body has various ways of getting rid of it.

Cool Tools for Studying Cells

Cell biologists would love to do what you just did—shrink down and actually see, touch, and hear the inner workings of cells. Because that's impossible, they've developed an ever-growing collection of approaches to study cellular innards from the outside. Among them are biochemistry, physical analysis, microscopy, computer analysis, and molecular genetics. Using these techniques, researchers can exhaustively inventory the individual molecular bits and pieces that make up cells, eavesdrop on cellular communication, and spy on cells as they adapt to changing environments. Together, the approaches provide vivid details about how cells work together in the body's organs and tissues. We'll start by discussing the traditional tools of the trade—microscopes—then touch on the new frontiers of quantum dots and computational biology.

Light Microscopes: The First Windows Into Cells

Robert Hooke, the British scientist who coined the word "cell," probably used this microscope when he prepared Micrographia. Published in 1665, Micrographia was the first book describing observations made through a microscope. It was a best-seller.

This fireworks explosion of color is a dividing newt lung cell seen under a light microscope and colored using fluorescent dyes: chromosomes in blue, intermediate filaments in red, and spindle fibers (bundled microtubules assembled for cell division) in green.

Scientists first saw cells by using traditional light microscopes. In fact, it was Robert Hooke (1635–1703), looking through a microscope at a thin slice of cork, who coined the word "cell." He chose the word to describe the boxlike holes in the plant cells because they reminded him of the cells of a monastery.

Scientists gradually got better at grinding glass into lenses and at whipping up chemicals to selectively stain cellular parts so they could see them better. By the late 1800s, biologists already had identified some of the largest organelles (the nucleus, mitochondria, and Golgi).
Researchers using high-tech light microscopes and glowing molecular labels can now watch biological processes in real time. The scientists start by chemically attaching a fluorescent dye or protein to a molecule that interests them. The colored glow then allows the scientists to locate the molecules in living cells and to track processes—such as cell movement, division, or infection—that involve the molecules.

Fluorescent labels come in many colors, including brilliant red, magenta, yellow, green, and blue. By using a collection of them at the same time, researchers can label multiple structures inside a cell and can track several processes at once. The technicolor result provides great insight into living cells—and is stunning cellular art.

Electron Microscopes: The Most Powerful of All

In the 1930s, scientists developed a new type of microscope, an electron microscope that allowed them to see beyond what some ever dreamed possible. The revolutionary concept behind the machine grew out of physicists' insights into the nature of electrons.

As its name implies, the electron microscope depends not on light, but on electrons. The microscopes accelerate electrons in a vacuum, shoot them out of an electron gun, and focus them with doughnut-shaped magnets. As the electrons bombard the sample, they are absorbed or scattered by different cell parts, forming an image on a detection plate.

Scanning electron microscopes allow scientists to see the three-dimensional surface of their samples.

Although electron microscopes enable scientists to see things hundreds of times smaller than anything visible through light microscopes, they have a serious drawback: They can't be used to study living cells. Biological tissues don't survive the technique's harsh chemicals, deadly vacuum, and powerful blast of electrons.

Electron microscopes come in two main flavors: transmission and scanning. Some transmission electron microscopes can magnify objects up to 1 million times, enabling scientists to see viruses and even some large molecules. To obtain this level of detail, however, the samples usually must be sliced so thin that they yield only flat, two-dimensional images. Photos from transmission electron microscopes are typically viewed in black and white.

Scanning electron microscopes cannot magnify samples as powerfully as transmission scopes, but they allow scientists to study the often intricate surface features of larger samples. This provides a window to see up close the three-dimensional terrain of intact cells, material surfaces, microscopic organisms, and insects. Scientists sometimes use computer drawing programs to highlight parts of these images with color.

Studying Single Molecules: Connecting the Quantum Dots

Dyes called quantum dots can simultaneously reveal the fine details of many cell structures. Here, the nucleus is blue, a specific protein within the nucleus is pink, mitochondria look yellow, microtubules are green, and actin filaments are red. Someday, the technique may be used for speedy disease diagnosis, DNA testing, or analysis of biological samples.

Whether they use microscopes, genetic methods, or any other technique to observe specific molecules, scientists typically flag every molecule of a certain type, then study these molecules as a group. It's rather like trying to understand a profession—say, teaching, architecture, or medicine—by tagging and observing all the workers in that profession simultaneously. Although these global approaches have taught us a lot, many scientists long to examine individual molecules in real time—the equivalent of following individual teachers as they go about their daily routines.

Now, new techniques are beginning to allow scientists to do just that. One technology, called quantum dots, uses microscopic semiconductor crystals to label specific proteins and genes. The crystals, each far less than a millionth of an inch in diameter, radiate brilliant colors when exposed to ultraviolet light. Dots of slightly different sizes glow in different fluorescent colors—larger dots shine red, while smaller dots shine blue, with a rainbow of colors in between. Researchers can create up to 40,000 different labels by mixing quantum dots of different colors and intensities as an artist would mix paint. In addition to coming in a vast array of colors, the dots also are brighter and more versatile than more traditional fluorescent dyes: They can be used to visualize individual molecules or, like the older labeling techniques, to visualize every molecule of a given type.

Quantum dots promise to advance not only cell biology but also a host of other areas. Someday, the technology may allow doctors to rapidly analyze thousands of genes and proteins from cancer patients and tailor treatments to each person's molecular profile. These bright dots also could help improve the speed, accuracy, and affordability of diagnostic tests for everything from HIV infection to allergies. And, when hitched to medicines, quantum dots might deliver a specific dose of a drug directly to a certain type of cell.

Computers Clarify Complexity

Say you're hungry and stranded in a blizzard: If you eat before you seek shelter, you might freeze to death, but if you don't eat first, you might not have the strength to get yourself out of the storm. That's analogous to the decisions cells have to make every day to survive.

For years, scientists have examined cell behaviors—like the response to cold or hunger—one at a time. And even that they did bit by bit, laboriously hammering out the specific roles of certain molecules. This approach made it difficult or impossible to study the relative contributions of—and the interplay between—genes that share responsibility for cell behaviors, such as the 100 or so genes involved in the control of blood pressure.

Now, computers are allowing scientists to examine many factors involved in cellular behaviors and decisions all at the same time. The field of computational biology blossomed with the advent of high-end computers. For example, sequencing the 3.2 billion base pairs of the human genome, which was completed in 2003, depended on computers advanced enough to tackle the challenge. Now, state-of-the-art equipment and a wealth of biological data from genome projects and other technologies are opening up many new research opportunities in computer analysis and modeling. So, much as microscopes and biochemical techniques revolutionized cell biology centuries ago, computers promise to advance the field just as dramatically in this new century.