Most people probably think of change when they hear the word evolution, but some of evolution's most amazing molecular inventions have stuck around hundreds of millions, even billions of years. The complex protein machinery needed to express genes, metabolize energy sources, reproduce sexually, and lay out body plans has remained in place largely unchanged in spite of the tremendous variety we see in the living world. These constant core cellular processes are why biologists could crack the universal genetic code by experimenting with bacteria, and why we gain insight into cell division and cancer by studying yeast.

The big question, argue the authors of The Plausibility of Life, is not how evolution keeps inventing new genes - it's how evolution can produce so much variety when the basic processes change so little. Later in the book Kirschner and Gerhart are going to argue that these basic systems have persisted so long because they are versatile, that they posses features which make them well-suited to facilitating the biological diversity we see today. We'll come to that argument later; today we'll take a closer look at the core conserved molecular systems that carry out the most basic cellular functions.

1. Metabolism and Gene Expression

When molecular biology was really taking off as a science, most of the field's future Nobel Laureates were doing their experiments with bacteria. The process of moving information from genes, encoded in DNA, to proteins, which carry out most of the physical work in the cell, is one of the oldest molecular systems around. All known organisms on earth use the same basic process to express genetic information: a gene is read out and transcribed into RNA by one set of proteins, including the critical one called RNA polymerase. The RNA is taken up into a large complex called a ribosome, and translated into protein.

All cells do this, and all cells use the same core protein machinery. There are many accessory proteins involved as well, and the accessory proteins are not always conserved. But the basic machinery is. Take for example, a piece of the ribosome: you can line up the protein sequence of the same piece from humans, yeast and bacteria, and you can see the similarity (each letter stands for a different amino acid; recall that a protein is a linear chain of amino acids):

How to read this: the little marks at the bottom indicate amino acids that are identical or chemically similar. Especially similar sequences are boxed in red.

The sequence is similar, and the proteins fold up into very similar final structures. Whether you are a human, yeast, or bacteria, you use the same basic proteins to express the information encoded in your DNA.

Not only do we share gene expression machinery with bacteria, we also share many of the chemical reactions and enzymes that power the cell. Many of the enzymes that break down sugar, as well the class of chemical wizards called the P450 cytochromes are found in all life.

What this means is that these incredibly useful systems were invented early in the history of life, and they have served all forms of life well ever since. Evolution doesn't have to reinvent proteins to metabolize sugar over and over; once was enough.

2. Sex, Chromosomes, and Cell Division

The next major evolutionary innovation that Kirchner and Gerhart note is the evolution of eukaryotic cells, that is, cells whose genetic material is packaged into chromosomes and kept in a nucleus. This was a major step forward, away from the bacterial lifestyle. Eukaryotes include single-celled critters like amoebas and yeast, as well as all plants, animals, and fungi (yeast are actually fungi).

The story here is the same: the basic protein machinery responsible for the unique features of eukaryotic cells are conserved in all eukaryotic cells. The proteins that package DNA into chromosomes and the proteins that control and carry out cell division have been conserved through one billion years of evolution.

Sex has been conserved as well. Not what we typically think of as sex, but the process at the cellular level arose long ago. For example, Yeast reproduce sexually - yeast are single cells, and don't make sperm or eggs, but they do undergo the same process of meiosis involved in producing human reproductive cells. After meiosis, two yeast cells can fuse to create a new organism with two copies of each chromosome, just like a fertilized human egg. From our perspective, this process is not what we imagine when we think of sex, but from system for sexual reproduction was invented about a billion years ago, and it has served eukaryotic cells well ever since.

3. Sticking Together: Multi-cellularity

The next major molecular innovation discussed by Kirschner and Gerhart is the development of organisms made up of more than one cell. This type of thing has happened multiple times in evolution. The evolution of animals and plants are the obvious examples, but it's also happened independently in fungi (mushrooms), and slime molds (and elsewhere).

There are many different ways to be multicellular, and at this point, Kirschner and Gerhart purposely limit their focus to animals. Animals are all multicellular in the same way, meaning that the same basic protein components that hold cells together and enable them to communicate with each other have remained the same. Sea urchin cells use the same molecular glue to holds cells together that we do, and they also use of the same cell-to-cell communication pathways.

4. Body Plans

Finally, the protein toolbox to make body plans - to determine front and back, top and bottom, to generate limbs or wings - was a major evolutionary invention that has been modified over and over (but never rebuilt from scratch) to create worms, starfish, flies, lizards, and us. For example, a regulatory protein called PAX6 is involved in making eyes in a mouse, and also makes eyes in flies.

This one of the most interesting lessons scientists have learned in the past two decades: the tremendous variety of animal body plans does not involve building new protein systems from scratch, it just involves tweaking existing ones. The system already in place has tremendous potential to produce millions of different body forms.

Detecting Evolution

How do we know these systems evolved? In truth, this is a side issue in our main intellectual thread; scientists generally are not interested in re-establishing evolution over and over again. That evolution occurs has been well-established by 150 years of scientific research. In contrast, understanding how evolution works is an area of active research, and this is the question that The Plausibility of Life is focused on.

Still, in the public arena the conversation keeps coming back to how scientists know evolution happens. There are many ways to answer this question, and here I'll focus on two lines of evidence for the antiquity of the major cellular systems we've just discussed.

1. The same but different: the pattern of differences and similarities in the gene sequences themselves are what we expect evolution to produce. We've just learned that the machinery involved in transferring information from DNA to proteins is essentially the same in all life, from bacteria to us. But the genes making up this machinery are not exactly the same, as you can see in the figure above: over time, mutations are going to change things, and after several billion years, differences have accumulated between the human and the bacterial versions of these genes.

Where those differences accumulate is the key clue: those parts of a gene most important for function have experienced little change, while the less-important portions change significantly. This is natural selection at work: a mutation that destroys the function of a critical gene will cripple an organism, while a mutation in a less important portion of the gene will accumulate as evolutionary noise.

The human and bacterial ribosome proteins do not look designed. The differences between the proteins are largely random differences, they are not differences important for making a human instead of a bacterium. You can't explain the pattern of similarities and differences by saying a designer made one version for just right for humans and one perfect for bacteria, because the differences between these two versions are random; they are not relevant to the function of the protein. The pattern of differences you see is what you expect evolution to produce.

And we can go further: look closely at the above figure again. You can see that the human and yeast proteins are more similar to each other than they are to the bacterial protein. This is because yeast and humans shared a common ancestor more recently than they shared a common ancestor with bacteria. The similarities and differences, found in the genes of all life, follow the pattern of a family tree. Your genes are more similar to the genes of your siblings than they are to the genes of your first cousins, and there are even more genetic differences between you and your second cousins. Why? Because you share more recent common ancestors with your siblings (the ancestors being your parents) than you do with your cousins (with your grandparents being the common ancestors in the case of first cousins, great-grandparents in the case of second cousins).

2. Molecules and fossils match: The family tree evident in the DNA of all life is reinforced by the fossil record. The protein machinery for controlling body plans discussed by Kirschner and Gerhart is shared by all animals, but not plants (which have a significantly different set of protein tools); thus this protein machinery probably evolved later than the evolutionary split between animals and plants. And that is in fact when animal body plans start showing up in the fossil record: much, much later than the split (seen in the fossil record) between animals and plants.

The order of invention of these conserved cellular processes (observable only with modern molecular biology technology) correlates stunningly well with the changes we see in the fossil record. And the genes involved in these core cellular processes show differences and similarities that follow the pattern of a family tree, very similar to the one that evolutionary biologists put together before we knew how to read the DNA sequences of genes.

Coming back to our main thread, we can see that, in spite of the huge variety we observe in the living world, several major core cellular systems were put in place early in life's history and have remained ever since. Is there something about these systems that makes them well-suited to producing novelty in evolution? Their existence would seem to make things easier: instead of reinventing complex systems from scratch to produce major new groups of organisms, evolution can use the same basic set of tools, over and over, to continually produce new modes of life.

This is the third installment of a series of posts on an interesting recent book by the accomplished biologists Marc Kirschner and John Gerhart. In this book, the authors lay out what they see as the most important research agenda for molecular biologists in the 21st century. Read Part 1 and Part 2.