Biology Explainer: The big 4 building blocks of life–carbohydrates, fats, proteins, and nucleic acids

The short version
  • The four basic categories of molecules for building life are carbohydrates, lipids, proteins, and nucleic acids.
  • Carbohydrates serve many purposes, from energy to structure to chemical communication, as monomers or polymers.
  • Lipids, which are hydrophobic, also have different purposes, including energy storage, structure, and signaling.
  • Proteins, made of amino acids in up to four structural levels, are involved in just about every process of life.                                                                                                      
  • The nucleic acids DNA and RNA consist of four nucleotide building blocks, and each has different purposes.
The longer version
Life is so diverse and unwieldy, it may surprise you to learn that we can break it down into four basic categories of molecules. Possibly even more implausible is the fact that two of these categories of large molecules themselves break down into a surprisingly small number of building blocks. The proteins that make up all of the living things on this planet and ensure their appropriate structure and smooth function consist of only 20 different kinds of building blocks. Nucleic acids, specifically DNA, are even more basic: only four different kinds of molecules provide the materials to build the countless different genetic codes that translate into all the different walking, swimming, crawling, oozing, and/or photosynthesizing organisms that populate the third rock from the Sun.

                                                  

Big Molecules with Small Building Blocks

The functional groups, assembled into building blocks on backbones of carbon atoms, can be bonded together to yield large molecules that we classify into four basic categories. These molecules, in many different permutations, are the basis for the diversity that we see among living things. They can consist of thousands of atoms, but only a handful of different kinds of atoms form them. It’s like building apartment buildings using a small selection of different materials: bricks, mortar, iron, glass, and wood. Arranged in different ways, these few materials can yield a huge variety of structures.

We encountered functional groups and the SPHONC in Chapter 3. These components form the four categories of molecules of life. These Big Four biological molecules are carbohydrates, lipids, proteins, and nucleic acids. They can have many roles, from giving an organism structure to being involved in one of the millions of processes of living. Let’s meet each category individually and discover the basic roles of each in the structure and function of life.
Carbohydrates

You have met carbohydrates before, whether you know it or not. We refer to them casually as “sugars,” molecules made of carbon, hydrogen, and oxygen. A sugar molecule has a carbon backbone, usually five or six carbons in the ones we’ll discuss here, but it can be as few as three. Sugar molecules can link together in pairs or in chains or branching “trees,” either for structure or energy storage.

When you look on a nutrition label, you’ll see reference to “sugars.” That term includes carbohydrates that provide energy, which we get from breaking the chemical bonds in a sugar called glucose. The “sugars” on a nutrition label also include those that give structure to a plant, which we call fiber. Both are important nutrients for people.

Sugars serve many purposes. They give crunch to the cell walls of a plant or the exoskeleton of a beetle and chemical energy to the marathon runner. When attached to other molecules, like proteins or fats, they aid in communication between cells. But before we get any further into their uses, let’s talk structure.

The sugars we encounter most in basic biology have their five or six carbons linked together in a ring. There’s no need to dive deep into organic chemistry, but there are a couple of essential things to know to interpret the standard representations of these molecules.

Check out the sugars depicted in the figure. The top-left molecule, glucose, has six carbons, which have been numbered. The sugar to its right is the same glucose, with all but one “C” removed. The other five carbons are still there but are inferred using the conventions of organic chemistry: Anywhere there is a corner, there’s a carbon unless otherwise indicated. It might be a good exercise for you to add in a “C” over each corner so that you gain a good understanding of this convention. You should end up adding in five carbon symbols; the sixth is already given because that is conventionally included when it occurs outside of the ring.

On the left is a glucose with all of its carbons indicated. They’re also numbered, which is important to understand now for information that comes later. On the right is the same molecule, glucose, without the carbons indicated (except for the sixth one). Wherever there is a corner, there is a carbon, unless otherwise indicated (as with the oxygen). On the bottom left is ribose, the sugar found in RNA. The sugar on the bottom right is deoxyribose. Note that at carbon 2 (*), the ribose and deoxyribose differ by a single oxygen.

The lower left sugar in the figure is a ribose. In this depiction, the carbons, except the one outside of the ring, have not been drawn in, and they are not numbered. This is the standard way sugars are presented in texts. Can you tell how many carbons there are in this sugar? Count the corners and don’t forget the one that’s already indicated!

If you said “five,” you are right. Ribose is a pentose (pent = five) and happens to be the sugar present in ribonucleic acid, or RNA. Think to yourself what the sugar might be in deoxyribonucleic acid, or DNA. If you thought, deoxyribose, you’d be right.

The fourth sugar given in the figure is a deoxyribose. In organic chemistry, it’s not enough to know that corners indicate carbons. Each carbon also has a specific number, which becomes important in discussions of nucleic acids. Luckily, we get to keep our carbon counting pretty simple in basic biology. To count carbons, you start with the carbon to the right of the non-carbon corner of the molecule. The deoxyribose or ribose always looks to me like a little cupcake with a cherry on top. The “cherry” is an oxygen. To the right of that oxygen, we start counting carbons, so that corner to the right of the “cherry” is the first carbon. Now, keep counting. Here’s a little test: What is hanging down from carbon 2 of the deoxyribose?

If you said a hydrogen (H), you are right! Now, compare the deoxyribose to the ribose. Do you see the difference in what hangs off of the carbon 2 of each sugar? You’ll see that the carbon 2 of ribose has an –OH, rather than an H. The reason the deoxyribose is called that is because the O on the second carbon of the ribose has been removed, leaving a “deoxyed” ribose. This tiny distinction between the sugars used in DNA and RNA is significant enough in biology that we use it to distinguish the two nucleic acids.

In fact, these subtle differences in sugars mean big differences for many biological molecules. Below, you’ll find a couple of ways that apparently small changes in a sugar molecule can mean big changes in what it does. These little changes make the difference between a delicious sugar cookie and the crunchy exoskeleton of a dung beetle.

Sugar and Fuel

A marathon runner keeps fuel on hand in the form of “carbs,” or sugars. These fuels provide the marathoner’s straining body with the energy it needs to keep the muscles pumping. When we take in sugar like this, it often comes in the form of glucose molecules attached together in a polymer called starch. We are especially equipped to start breaking off individual glucose molecules the minute we start chewing on a starch.

Double X Extra: A monomer is a building block (mono = one) and a polymer is a chain of monomers. With a few dozen monomers or building blocks, we get millions of different polymers. That may sound nutty until you think of the infinity of values that can be built using only the numbers 0 through 9 as building blocks or the intricate programming that is done using only a binary code of zeros and ones in different combinations.

Our bodies then can rapidly take the single molecules, or monomers, into cells and crack open the chemical bonds to transform the energy for use. The bonds of a sugar are packed with chemical energy that we capture to build a different kind of energy-containing molecule that our muscles access easily. Most species rely on this process of capturing energy from sugars and transforming it for specific purposes.

Polysaccharides: Fuel and Form

Plants use the Sun’s energy to make their own glucose, and starch is actually a plant’s way of storing up that sugar. Potatoes, for example, are quite good at packing away tons of glucose molecules and are known to dieticians as a “starchy” vegetable. The glucose molecules in starch are packed fairly closely together. A string of sugar molecules bonded together through dehydration synthesis, as they are in starch, is a polymer called a polysaccharide (poly = many; saccharide = sugar). When the monomers of the polysaccharide are released, as when our bodies break them up, the reaction that releases them is called hydrolysis.

Double X Extra: The specific reaction that hooks one monomer to another in a covalent bond is called dehydration synthesis because in making the bond–synthesizing the larger molecule–a molecule of water is removed (dehydration). The reverse is hydrolysis (hydro = water; lysis = breaking), which breaks the covalent bond by the addition of a molecule of water.

Although plants make their own glucose and animals acquire it by eating the plants, animals can also package away the glucose they eat for later use. Animals, including humans, store glucose in a polysaccharide called glycogen, which is more branched than starch. In us, we build this energy reserve primarily in the liver and access it when our glucose levels drop.

Whether starch or glycogen, the glucose molecules that are stored are bonded together so that all of the molecules are oriented the same way. If you view the sixth carbon of the glucose to be a “carbon flag,” you’ll see in the figure that all of the glucose molecules in starch are oriented with their carbon flags on the upper left.

The orientation of monomers of glucose in polysaccharides can make a big difference in the use of the polymer. The glucoses in the molecule on the top are all oriented “up” and form starch. The glucoses in the molecule on the bottom alternate orientation to form cellulose, which is quite different in its function from starch.

Storing up sugars for fuel and using them as fuel isn’t the end of the uses of sugar. In fact, sugars serve as structural molecules in a huge variety of organisms, including fungi, bacteria, plants, and insects.

The primary structural role of a sugar is as a component of the cell wall, giving the organism support against gravity. In plants, the familiar old glucose molecule serves as one building block of the plant cell wall, but with a catch: The molecules are oriented in an alternating up-down fashion. The resulting structural sugar is called cellulose.

That simple difference in orientation means the difference between a polysaccharide as fuel for us and a polysaccharide as structure. Insects take it step further with the polysaccharide that makes up their exoskeleton, or outer shell. Once again, the building block is glucose, arranged as it is in cellulose, in an alternating conformation. But in insects, each glucose has a little extra added on, a chemical group called an N-acetyl group. This addition of a single functional group alters the use of cellulose and turns it into a structural molecule that gives bugs that special crunchy sound when you accidentally…ahem…step on them.

These variations on the simple theme of a basic carbon-ring-as-building-block occur again and again in biological systems. In addition to serving roles in structure and as fuel, sugars also play a role in function. The attachment of subtly different sugar molecules to a protein or a lipid is one way cells communicate chemically with one another in refined, regulated interactions. It’s as though the cells talk with each other using a specialized, sugar-based vocabulary. Typically, cells display these sugary messages to the outside world, making them available to other cells that can recognize the molecular language.

Lipids: The Fatty Trifecta

Starch makes for good, accessible fuel, something that we immediately attack chemically and break up for quick energy. But fats are energy that we are supposed to bank away for a good long time and break out in times of deprivation. Like sugars, fats serve several purposes, including as a dense source of energy and as a universal structural component of cell membranes everywhere.

Fats: the Good, the Bad, the Neutral

Turn again to a nutrition label, and you’ll see a few references to fats, also known as lipids. (Fats are slightly less confusing that sugars in that they have only two names.) The label may break down fats into categories, including trans fats, saturated fats, unsaturated fats, and cholesterol. You may have learned that trans fats are “bad” and that there is good cholesterol and bad cholesterol, but what does it all mean?

Let’s start with what we mean when we say saturated fat. The question is, saturated with what? There is a specific kind of dietary fat call the triglyceride. As its name implies, it has a structural motif in which something is repeated three times. That something is a chain of carbons and hydrogens, hanging off in triplicate from a head made of glycerol, as the figure shows.  Those three carbon-hydrogen chains, or fatty acids, are the “tri” in a triglyceride. Chains like this can be many carbons long.

Double X Extra: We call a fatty acid a fatty acid because it’s got a carboxylic acid attached to a fatty tail. A triglyceride consists of three of these fatty acids attached to a molecule called glycerol. Our dietary fat primarily consists of these triglycerides.

Triglycerides come in several forms. You may recall that carbon can form several different kinds of bonds, including single bonds, as with hydrogen, and double bonds, as with itself. A chain of carbon and hydrogens can have every single available carbon bond taken by a hydrogen in single covalent bond. This scenario of hydrogen saturation yields a saturated fat. The fat is saturated to its fullest with every covalent bond taken by hydrogens single bonded to the carbons.

Saturated fats have predictable characteristics. They lie flat easily and stick to each other, meaning that at room temperature, they form a dense solid. You will realize this if you find a little bit of fat on you to pinch. Does it feel pretty solid? That’s because animal fat is saturated fat. The fat on a steak is also solid at room temperature, and in fact, it takes a pretty high heat to loosen it up enough to become liquid. Animals are not the only organisms that produce saturated fat–avocados and coconuts also are known for their saturated fat content.

The top graphic above depicts a triglyceride with the glycerol, acid, and three hydrocarbon tails. The tails of this saturated fat, with every possible hydrogen space occupied, lie comparatively flat on one another, and this kind of fat is solid at room temperature. The fat on the bottom, however, is unsaturated, with bends or kinks wherever two carbons have double bonded, booting a couple of hydrogens and making this fat unsaturated, or lacking some hydrogens. Because of the space between the bumps, this fat is probably not solid at room temperature, but liquid.

You can probably now guess what an unsaturated fat is–one that has one or more hydrogens missing. Instead of single bonding with hydrogens at every available space, two or more carbons in an unsaturated fat chain will form a double bond with carbon, leaving no space for a hydrogen. Because some carbons in the chain share two pairs of electrons, they physically draw closer to one another than they do in a single bond. This tighter bonding result in a “kink” in the fatty acid chain.

In a fat with these kinks, the three fatty acids don’t lie as densely packed with each other as they do in a saturated fat. The kinks leave spaces between them. Thus, unsaturated fats are less dense than saturated fats and often will be liquid at room temperature. A good example of a liquid unsaturated fat at room temperature is canola oil.

A few decades ago, food scientists discovered that unsaturated fats could be resaturated or hydrogenated to behave more like saturated fats and have a longer shelf life. The process of hydrogenation–adding in hydrogens–yields trans fat. This kind of processed fat is now frowned upon and is being removed from many foods because of its associations with adverse health effects. If you check a food label and it lists among the ingredients “partially hydrogenated” oils, that can mean that the food contains trans fat.

Double X Extra: A triglyceride can have up to three different fatty acids attached to it. Canola oil, for example, consists primarily of oleic acid, linoleic acid, and linolenic acid, all of which are unsaturated fatty acids with 18 carbons in their chains.

Why do we take in fat anyway? Fat is a necessary nutrient for everything from our nervous systems to our circulatory health. It also, under appropriate conditions, is an excellent way to store up densely packaged energy for the times when stores are running low. We really can’t live very well without it.

Phospholipids: An Abundant Fat

You may have heard that oil and water don’t mix, and indeed, it is something you can observe for yourself. Drop a pat of butter–pure saturated fat–into a bowl of water and watch it just sit there. Even if you try mixing it with a spoon, it will just sit there. Now, drop a spoon of salt into the water and stir it a bit. The salt seems to vanish. You’ve just illustrated the difference between a water-fearing (hydrophobic) and a water-loving (hydrophilic) substance.

Generally speaking, compounds that have an unequal sharing of electrons (like ions or anything with a covalent bond between oxygen and hydrogen or nitrogen and hydrogen) will be hydrophilic. The reason is that a charge or an unequal electron sharing gives the molecule polarity that allows it to interact with water through hydrogen bonds. A fat, however, consists largely of hydrogen and carbon in those long chains. Carbon and hydrogen have roughly equivalent electronegativities, and their electron-sharing relationship is relatively nonpolar. Fat, lacking in polarity, doesn’t interact with water. As the butter demonstrated, it just sits there.

There is one exception to that little maxim about fat and water, and that exception is the phospholipid. This lipid has a special structure that makes it just right for the job it does: forming the membranes of cells. A phospholipid consists of a polar phosphate head–P and O don’t share equally–and a couple of nonpolar hydrocarbon tails, as the figure shows. If you look at the figure, you’ll see that one of the two tails has a little kick in it, thanks to a double bond between the two carbons there.

Phospholipids form a double layer and are the major structural components of cell membranes. Their bend, or kick, in one of the hydrocarbon tails helps ensure fluidity of the cell membrane. The molecules are bipolar, with hydrophilic heads for interacting with the internal and external watery environments of the cell and hydrophobic tails that help cell membranes behave as general security guards.

The kick and the bipolar (hydrophobic and hydrophilic) nature of the phospholipid make it the perfect molecule for building a cell membrane. A cell needs a watery outside to survive. It also needs a watery inside to survive. Thus, it must face the inside and outside worlds with something that interacts well with water. But it also must protect itself against unwanted intruders, providing a barrier that keeps unwanted things out and keeps necessary molecules in.

Phospholipids achieve it all. They assemble into a double layer around a cell but orient to allow interaction with the watery external and internal environments. On the layer facing the inside of the cell, the phospholipids orient their polar, hydrophilic heads to the watery inner environment and their tails away from it. On the layer to the outside of the cell, they do the same.
As the figure shows, the result is a double layer of phospholipids with each layer facing a polar, hydrophilic head to the watery environments. The tails of each layer face one another. They form a hydrophobic, fatty moat around a cell that serves as a general gatekeeper, much in the way that your skin does for you. Charged particles cannot simply slip across this fatty moat because they can’t interact with it. And to keep the fat fluid, one tail of each phospholipid has that little kick, giving the cell membrane a fluid, liquidy flow and keeping it from being solid and unforgiving at temperatures in which cells thrive.

Steroids: Here to Pump You Up?

Our final molecule in the lipid fatty trifecta is cholesterol. As you may have heard, there are a few different kinds of cholesterol, some of which we consider to be “good” and some of which is “bad.” The good cholesterol, high-density lipoprotein, or HDL, in part helps us out because it removes the bad cholesterol, low-density lipoprotein or LDL, from our blood. The presence of LDL is associated with inflammation of the lining of the blood vessels, which can lead to a variety of health problems.

But cholesterol has some other reasons for existing. One of its roles is in the maintenance of cell membrane fluidity. Cholesterol is inserted throughout the lipid bilayer and serves as a block to the fatty tails that might otherwise stick together and become a bit too solid.

Cholesterol’s other starring role as a lipid is as the starting molecule for a class of hormones we called steroids or steroid hormones. With a few snips here and additions there, cholesterol can be changed into the steroid hormones progesterone, testosterone, or estrogen. These molecules look quite similar, but they play very different roles in organisms. Testosterone, for example, generally masculinizes vertebrates (animals with backbones), while progesterone and estrogen play a role in regulating the ovulatory cycle.

Double X Extra: A hormone is a blood-borne signaling molecule. It can be lipid based, like testosterone, or short protein, like insulin.

Proteins

As you progress through learning biology, one thing will become more and more clear: Most cells function primarily as protein factories. It may surprise you to learn that proteins, which we often talk about in terms of food intake, are the fundamental molecule of many of life’s processes. Enzymes, for example, form a single broad category of proteins, but there are millions of them, each one governing a small step in the molecular pathways that are required for living.

Levels of Structure

Amino acids are the building blocks of proteins. A few amino acids strung together is called a peptide, while many many peptides linked together form a polypeptide. When many amino acids strung together interact with each other to form a properly folded molecule, we call that molecule a protein.

For a string of amino acids to ultimately fold up into an active protein, they must first be assembled in the correct order. The code for their assembly lies in the DNA, but once that code has been read and the amino acid chain built, we call that simple, unfolded chain the primary structure of the protein.

This chain can consist of hundreds of amino acids that interact all along the sequence. Some amino acids are hydrophobic and some are hydrophilic. In this context, like interacts best with like, so the hydrophobic amino acids will interact with one another, and the hydrophilic amino acids will interact together. As these contacts occur along the string of molecules, different conformations will arise in different parts of the chain. We call these different conformations along the amino acid chain the protein’s secondary structure.

Once those interactions have occurred, the protein can fold into its final, or tertiary structure and be ready to serve as an active participant in cellular processes. To achieve the tertiary structure, the amino acid chain’s secondary interactions must usually be ongoing, and the pH, temperature, and salt balance must be just right to facilitate the folding. This tertiary folding takes place through interactions of the secondary structures along the different parts of the amino acid chain.

The final product is a properly folded protein. If we could see it with the naked eye, it might look a lot like a wadded up string of pearls, but that “wadded up” look is misleading. Protein folding is a carefully regulated process that is determined at its core by the amino acids in the chain: their hydrophobicity and hydrophilicity and how they interact together.

In many instances, however, a complete protein consists of more than one amino acid chain, and the complete protein has two or more interacting strings of amino acids. A good example is hemoglobin in red blood cells. Its job is to grab oxygen and deliver it to the body’s tissues. A complete hemoglobin protein consists of four separate amino acid chains all properly folded into their tertiary structures and interacting as a single unit. In cases like this involving two or more interacting amino acid chains, we say that the final protein has a quaternary structure. Some proteins can consist of as many as a dozen interacting chains, behaving as a single protein unit.

A Plethora of Purposes

What does a protein do? Let us count the ways. Really, that’s almost impossible because proteins do just about everything. Some of them tag things. Some of them destroy things. Some of them protect. Some mark cells as “self.” Some serve as structural materials, while others are highways or motors. They aid in communication, they operate as signaling molecules, they transfer molecules and cut them up, they interact with each other in complex, interrelated pathways to build things up and break things down. They regulate genes and package DNA, and they regulate and package each other.

As described above, proteins are the final folded arrangement of a string of amino acids. One way we obtain these building blocks for the millions of proteins our bodies make is through our diet. You may hear about foods that are high in protein or people eating high-protein diets to build muscle. When we take in those proteins, we can break them apart and use the amino acids that make them up to build proteins of our own.

Nucleic Acids

How does a cell know which proteins to make? It has a code for building them, one that is especially guarded in a cellular vault in our cells called the nucleus. This code is deoxyribonucleic acid, or DNA. The cell makes a copy of this code and send it out to specialized structures that read it and build proteins based on what they read. As with any code, a typo–a mutation–can result in a message that doesn’t make as much sense. When the code gets changed, sometimes, the protein that the cell builds using that code will be changed, too.

Biohazard!The names associated with nucleic acids can be confusing because they all start with nucle-. It may seem obvious or easy now, but a brain freeze on a test could mix you up. You need to fix in your mind that the shorter term (10 letters, four syllables), nucleotide, refers to the smaller molecule, the three-part building block. The longer term (12 characters, including the space, and five syllables), nucleic acid, which is inherent in the names DNA and RNA, designates the big, long molecule.

DNA vs. RNA: A Matter of Structure

DNA and its nucleic acid cousin, ribonucleic acid, or RNA, are both made of the same kinds of building blocks. These building blocks are called nucleotides. Each nucleotide consists of three parts: a sugar (ribose for RNA and deoxyribose for DNA), a phosphate, and a nitrogenous base. In DNA, every nucleotide has identical sugars and phosphates, and in RNA, the sugar and phosphate are also the same for every nucleotide.

So what’s different? The nitrogenous bases. DNA has a set of four to use as its coding alphabet. These are the purines, adenine and guanine, and the pyrimidines, thymine and cytosine. The nucleotides are abbreviated by their initial letters as A, G, T, and C. From variations in the arrangement and number of these four molecules, all of the diversity of life arises. Just four different types of the nucleotide building blocks, and we have you, bacteria, wombats, and blue whales.

RNA is also basic at its core, consisting of only four different nucleotides. In fact, it uses three of the same nitrogenous bases as DNA–A, G, and C–but it substitutes a base called uracil (U) where DNA uses thymine. Uracil is a pyrimidine.

DNA vs. RNA: Function Wars

An interesting thing about the nitrogenous bases of the nucleotides is that they pair with each other, using hydrogen bonds, in a predictable way. An adenine will almost always bond with a thymine in DNA or a uracil in RNA, and cytosine and guanine will almost always bond with each other. This pairing capacity allows the cell to use a sequence of DNA and build either a new DNA sequence, using the old one as a template, or build an RNA sequence to make a copy of the DNA.

These two different uses of A-T/U and C-G base pairing serve two different purposes. DNA is copied into DNA usually when a cell is preparing to divide and needs two complete sets of DNA for the new cells. DNA is copied into RNA when the cell needs to send the code out of the vault so proteins can be built. The DNA stays safely where it belongs.

RNA is really a nucleic acid jack-of-all-trades. It not only serves as the copy of the DNA but also is the main component of the two types of cellular workers that read that copy and build proteins from it. At one point in this process, the three types of RNA come together in protein assembly to make sure the job is done right.


 By Emily Willingham, DXS managing editor 
This material originally appeared in similar form in Emily Willingham’s Complete Idiot’s Guide to College Biology

Cottoning on to genome duplications

Cotton, courtesy of the USDA.
What do electrons have to do with our ability to spin this into yarn?
Image via Wikimedia Commons.
 
by Chris Gunter, Science Education Editor, DXS

 

Plants are hard. Not in the physical way, but in the genomics way: It’s been estimated that 75% of domesticated plant genomes are polyploid, meaning they have up to 12 sets of each chromosome in every cell. This makes genome sequencing crazily difficult: Each gene segment is represented multiple times, and each one has changes between them, since these organisms multiplied their chromosomes millions of years ago.
Photo of one of the institutions involved, the HudsonAlpha Institute
for Biotechnology (and my employer), through our backyard cotton field.
Credit: Holly Ralston
 
Every genome sequence has errors produced along the way; it’s just a factor of the technology and the scale involved. When you are trying to read the genome of a plant and you see a nucleotide position with multiple bases supposedly reported by the sequencer at that position, how do you know what’s real and what’s error?
 
Enter comparative genomics. Scientists around the world are attacking this problem by sequencing as many different plants as possible and comparing the genomes to each other across evolutionary time. This week, the plant in the spotlight is cotton, or the Gossypium genus. Scientists from 10 countries collaborated to produce a draft genome sequence for Gossypium raimondii, which produces a non-spinnable variety of cotton fiber.
 
The cotton genome produced is much larger than other plants that have been sequenced – poplar, rice, and grapevines – and in this case 61% of its genome size comes from repetitive elements, which are also quite hard to incorporate into a genome sequence. It’s a little like putting together a multi-million piece jigsaw puzzle where over half the picture is blue sky. In the unique parts of the genome are over 37,000 genes, which is at least 10,000 more than humans.
 
By comparing this more complete genome sequence to other plants, the researchers can conclude that what we now know as cotton has gone through multiple transformations. At least 60 million years ago, its ancestors diverged from other plants and went through an abrupt chromosome multiplication, to have the five or six sets of chromosomes we still see today.
 
Then, about 5-10 million years ago, fibers with a structure that allowed them to be spinnable into yarn evolved in some cotton subgroups and not others. To investigate what makes spinnable cotton, the researchers produced some genome sequence for a number of representatives of these subgroups. Intriguingly, they saw linkage between fiber quality and a block of mitochondrial genes that had transported to the nucleus of some cotton strains. Mitochondria are the structures in the cell that take nutrient energy and package it into molecules that cells can use as an energy source.
 
In the case of cotton, the co-opted mitochondrial genes relate to the way cells like ours and those of plants generate those energy-containing molecules, by transport of electrons through certain enzymes (like NADH dehydrogenase for you aficionados). There is no obvious connection between the observations about electrons and the spinnability of cotton, though, leaving open the question: Can this passage of electrons from protein to protein really be involved in allowing our own ancestors to start making clothes from cotton? Now that these genome data have been released, anyone can study them for an answer.
 
The paper is freely available on the website of the journal Nature and is entitled “Repeated polyploidization of Gossypium genomes and the evolution of spinnable cotton fibres.” 

Why being a Nature editor is like riding the Knight Bus

 
Have you seen a picture of our science education editor, Chris Gunter (above)? She looks kinda nice, doesn’t she? Would it surprise you to learn that once upon a time, she was viewed along the lines of the love child between a rock goddess and Darth Vader? Perhaps picture Grace Slick in a long black cape, glaring at you. Like this:
 
Via Wikimedia Commons.
Why was Chris such a badass? Because she was an editor at Nature, science’s toppest-tier journal, for almost seven years, dealing with submissions in the genetics/genomics side of things. You might be surprised to learn, as Chris relates in telling about her experiences at Story Collider, which features compelling stories about science, that what sounds like an intensely precise and technical field generated “mountains of drama.” In telling her tale, Chris likens her experience to riding the Knight Bus in Harry Potter, in which you’re never quite sure who your seat mate will be. She writes, 

People ask me all the time what the job was like. The best analogy I’ve I found is riding the Knight Bus in Harry Potter. The Knight Bus is the magical transport full of crazy people and events, both amazingly good and scarily over the top. Similarly, I felt like I was on this magical transport that went to the wildest places, and every week I’d think, “There is absolutely no way we will get to our destination” of putting out a magazine. Yet, thanks in part to the skillful drivers on the editorial and production teams, every week we did arrive at the publication of an issue, and it was an exhilarating ride.

For more about Chris and her experiences on the Knight Bus … er, at Nature … read on over at Story Collider, where her story has been filed under “Stress.” For good reason.

 

The Bright Crystal

The crazy-complicated structure of the ribosome, solved by x-ray crystallography (Source
Drug development used to be accomplished by the chemical equivalent of what you might call the spaghetti method: Throw a bunch of molecules against the wall and see what sticks. More recently, pharmaceutical companies have applied a more rational approach, using the molecular structures of drug targets to design molecules that “fit” them like a lock to a key.
The technique most often used to solve those molecular structures is x-ray crystallography. With this approach, which turned 100 years old in November, a high-powered beam of x-rays is shot at a crystal of protein molecules. The x-rays collide with the crystal’s atoms, scattering at specific angles. Working backwards from that information, researchers can figure out the original structure.
Over at Boing Boing, Maggie Koerth-Baker recently came up with a really fantastic analogy to explain this idea. X-ray crystallography, she wrote, is

… a method of determining the shape and structure of things that we can’t see with our own eyes. Imagine that you have captured Wonder Woman’s invisible airplane. You can’t see it. But you know it’s there because when you throw a rubber ball at the space, the ball bounces back to you. If you could throw enough rubber balls, from all different sides, and measure their trajectory and speed as they bounced back, you could probably get a pretty good idea of the shape of the plane.

(Source)
Anyhoo, as the name of the technique implies, the key to crystallography is, well, crystals. But not all proteins crystallize, and even with those that do, it can be hard to grow crystals large enough for the technique to work.
Recently, though, a pair of technology developments have made it possible (in some cases) to work around these problems.

The first development was the commissioning in the past few years of ultra-bright x-ray sources in California (the Linac Coherent Light Source at Stanford) and Japan. These so-called “x-ray free electron lasers” (X-FELs) shoot incredibly bright, incredibly short x-ray pulses, pulses that are so intense that they destroy a sample in a fraction of a second, but not before the x-rays (which travel at the speed of light, natch) have bounced off of it.

The reason crystals are required in crystallography is that any one diffraction event is hard to see. The regularly spaced molecules inside a crystal amplify that relatively weak signal, simplifying detection and structure determination. As it turns out, the brighter an x-ray source, the smaller the crystal required to obtain such data has to be, and with X-FELs, the crystals can be very small indeed – on the order of millionths of a meter (micrometers) in size, and perhaps even smaller.

Which brings me to the second development. In the March issue of the journal Nature Methods, a team of researchers led by Michael Duszenko in Germany showed that some proteins that cannot crystallize in a test tube will crystallize inside insect cells. Protein chemists often use cells as molecular factories to obtain large quantities of protein. But the goal is to extract the protein from the cells, not have them crystalize inside of them. Generally speaking, protein crystallization inside cells is a bad thing, the kind of thing researchers really don’t want to see; Duszenko and his team are the first to capitalize on this so-called “in vivo crystallization” phenomenon.

The crystals Duszenko’s team collected are quite small, of course –- they fit inside cells, after all — and in that initial study, they were on the order of 1 micrometer wide and 15 micrometers long. But as it turns out, they are big enough for the X-FEL. In the March paper, the team showed that these crystals will diffract x-rays in the X-FEL, but they didn’t solve the resulting structure.

Now, in a paper published Nov. 29 in Science, they have. They did it by combining X-FEL and in vivo crystallization to solve the structure of a trypsanosomal enzyme called cathepsin-B, a potential drug target for African sleeping sickness.

The team sprayed a stream of tiny enzyme crystals (each about 1 x 1 x 11 micrometers) into the path of the X-FEL, which fired discrete pulses of x-ray, each just 40 femtoseconds, or 0.000000000000040 seconds long, 120 times per second. Every so often, one of those pulses would collide with a crystal, and a nearby camera would capture the event.

Serial femtosecond crystallography (Source Continue reading

Drill, baby, drill — microbial-style

Could the oil energy needed to light up this drill
come directly from soil bacteria instead of the soil?
Image credit: Obakeneko; via Wikimedia Commons

By Jeffrey Perkel, DXS tech editor

It’s no secret that America’s petroleum addiction is a problem in need of a solution. “Drill, baby, drill” notwithstanding, this country eventually will have to find a way to survive without low-cost oil – or at least, find another way to make it.


A recent MIT press release suggests one route to energy independence: soil bacteria. The release, Teaching a microbe to make fuel,” details a recent study from MIT graduate student Jingnan Lu, research scientist Christopher Brigham, and their lab director, Anthony Sinskey.

What Brigham, Lu, and their colleagues did was convince a soil bacterium called Ralstonia eutropha to turn carbon into gasoline –- specifically, the four-carbon molecules iso-butanol and 3-methyl-1-butanol.


Ralstonia eutropha bacteria in culture
How’d they do that? It was a simple matter of microbial engineering. As detailed in MIT’s description:
… in the microbe’s natural state, when its source of essential nutrients such as nitrate or phosphate is restricted, “it will go into carbon-storage mode,” [Brigham says,] essentially storing away food for later use when it senses that resources are limited. 
 “What it does is take whatever carbon is available, and stores it in the form of a polymer, which is similar in its properties to a lot of petroleum-based plastics,” Brigham says. By knocking out a few genes, inserting a gene from another organism and tinkering with the expression of other genes, Brigham and his colleagues were able to redirect the microbe to make fuel instead of plastic.

That last sentence makes the process sound easier than it was. It took a full year of work to effect that transformation, Brigham tells me, and no wonder: Bacteria don’t normally make gasoline. But they do make amino acids, the protein building blocks that all living things need to survive. The team realized that Ralstonia bacteria create one particular group of amino acids (the so-called branched-chain amino acids) using chemical intermediates that they could coopt to turn sugar into fuel.


To realize that potential, Brigham and his colleagues first had to get Ralstonia to refocus its energies, literally. When stressed, the bacteria store carbon in a polymer–a chain of molecules–called PHB. The bacterium executes this particular biochemical program extremely effectively, cranking out enough polymer to account for more than 80% of the cell’s mass. Brigham and Lu had to redirect that enzymatic zeal towards gasoline instead. So, they knocked out the genes involved in building PHB.


Next, they added some missing chemical pieces. I said earlier that the branched-chain amino acid pathway includes an intermediate that could be used to make gasoline. To do that, the cells need a missing bit of hardware — specifically, an enzyme to convert that chemical intermediate into something the gasoline-making enzymes can use. That enzyme is called KIVD, and Ralstonia does not make it. But another bacterium, Lactococcus lactis, does make it. Brigham and Lu borrowed the related bit of genetic material from Lactococcus lactis, expressed it in Ralstonia, and –- not much happened.

As University of California, Berkeley, biochemical engineer Jay Keasling explained to me, the cell in such situations is literally a chemical factory. For the factory to run smoothly, all the factory workers –- the enzymes -– need to be fully engaged at the right time. That won’t happen if one enzyme is cranking out lots of its product but others are not. Intermediate products will start piling up, reducing efficiency and potentially poisoning the cell.


In this case, with KIVD, the cells had all the necessary pieces to make gasoline. But they weren’t producing them at the same levels. In other words, the factory had more workers at one part of the assembly line than at others. As a result, productivity was relatively low (about 10 mg isobutanol per liter of culture). To boost that output, the researchers dialed up expression levels of several proteins to get them all in sync. They also shut down a handful of other chemical assembly lines, too, “carbon sinks” that could siphon off intermediates.


When all was said and done, the cells could produce about 310 mg of gasoline per liter of culture. That gas conveniently drifts into the culture medium surrounding the cells, from which it is easily extracted. Now, says Brigham, the trick is optimizing the process.


In the meantime, others are working towards the same goal. Researchers have considerable experience getting bacteria and yeast to produce compounds they don’t normally make — the antimalarial drug artemisinin, for instance -– and microbial biofuel development is a research target at the Joint BioEnergy Institute (headed by Keasling), Synthetic Genomics, and LS9, among other places.


Often, those biofuel strategies rely on plants to produce their starting materials. And that’s the really cool part about Sinskey’s work: Ralstonia can eat almost anything, Brigham says, from carbon dioxide and organic acids to fatty acids and sugar. Brigham envisions coupling these organisms to waste streams, such that they can suck out the nutrients and turn them into fuel, no plants required.


Garbage in, fuel out: Now that’s a microbial trick I can get behind. 


(If you’re interested, you can read Brigham and Lu’s work here.)


Image: Christopher Brigham / http://web.mit.edu/newsoffice/2012/genetically-modified-organism-can-turn-carbon-dioxide-into-fuel-0821.html