The Logic of Organisms

Life is a history of change over time. That change moves in the direction of complexity.

We can observe these truths plain enough in the course of our own lives. But we owe it to Charles Darwin and his Victorian colleague Alfred Wallace that we can trace them on timescales reaching back millions of years.

In classical evolutionary theory, "descent with modification" explains the origin of new species and ultimately the vast diversity of the biological world. Yet Darwin's was only the first step, Ken Weiss said. "He knew that this evolution required something to be inherited, but he didn't know what it was."

Weiss, who is Evan Pugh professor of anthropology and genetics at Penn State, delivered the third installment of "Change Happens: Understanding How Living Things Evolve," the 2006 edition of the Penn State Lectures on the Frontiers of Science. In the first few minutes of his talk, he traced a scientific lineage from The Origin of Species to the present day.

"In the 1930s," he said, "a field called population genetics was developed, and that showed how genes—whatever they were—evolve through history, that genetic variation arises, is transmitted from one generation to the next, and that populations evolve by a process of natural selection."

Then came the dramatic discovery of DNA's structure: The genes we inherit were modular units of amino-acid sequences, arranged in very long molecules called chromosomes which, added together, make up the genome, "the repository of evolutionary memory."

Together these theories made sense of evolution. "But none of them provided a phenogenetic understanding of life," Weiss said. None of them could describe in detail the relationship between genes and the traits they produce.

A young woman intently bowing a violinthe middle of a lush wood
Ken Weiss

A profusion of life's rich diversity, the result of duplication with variation. The violinist is Ken Weiss's daughter, Amie, a professional musician

An image flashed on the screen above his head. On the left, an undifferentiated block of DNA code; on the right,
a young woman intently bowing a violinthe middle of a lush wood. "How exactly does this"—he pointed to the block of A's, T's, G's, and C's—"become this?"—and he pointed to the violinist. "How does this string of billions of nucleotides translate into the diversity of life?

"To answer this question we can't just look at evolution," Weiss said. "We have to look at development"—at how an individual organism develops from a single 'general' cell into a coordinated unit of billions of specialized cells.

"Above all, organisms are differentiated entities," he said. "So making cells differentiate is the main job of development and, in a way, the main job of genes."

Complexity made simple?

It's because of recent technical advances in molecular genetics—including the publication of whole-genome sequences for a growing number of species—that understanding how genes do their job is beginning to be possible. "In essence," Weiss has written, "these methods have revealed the nature, use, and mechanisms of differential gene expression in cells, complex organisms, and systems."

A set of fundamental principles has emerged, elements of what Weiss calls "the logic of organisms." What's become clear, he said, "is that cells can change into more complex forms by undergoing some very simple processes."

Evolution genome
Reproduced with permission from Nature Reviews Genetics 6, 36-45 copyright 2005 Macmillan Magazines Ltd.

Basic principles of phenogenetic logic. (a) Modularity is ubiquitous in the genome. A schematic representation of a region of a chromosome illustrates the kinds of modular units that are typically found. (b) Most gene expression involves arbitrary combinatorial coding. Labels identify proteins that are used in signalling. The signalling code specifies expression of the final gene (red rectangle within the nucleus).

In the long view, "genomes are the modular product of billions of years of duplication events," Weiss explained. Across the generations, the code is copied out again and again and again, and there are foul-ups in the process—mutations. "Pieces can be rearranged, break off, rejoin, be copied twice. This doesn't happen often," he said, "but it happens often enough for evolution to take place."

The eventual product is a string of modular units, "like a necklace with different colored beads on it. And these modules directly and indirectly correspond to structures and functions in organisms."

That's the part where the logic comes in. By and large, Weiss said, genes aren't independent functional units that translate directly into traits. Rather, traits are produced by combinations of genes interacting. "A fundamental aspect of development," he explained, "is that each of your cells has all of these genes, the full set of 3.1 billion nucleotides, but it only uses a subset of them. That's how a liver cell and a skin cell are different: They have the same genes, but they use different combinations of them."

"Most genes have general rather than specific functions," he added. "Of those we know, a large percentage have to do with regulating other genes, or signaling to other cells—not with making the stiff stuff in your skin or the pigment in your eye."

Much of the action of development, he went on, takes place not inside the cell nucleus where the chromosomes dwell, but outside the cell. There, signaling factors sent by other cells find the right receptor on the cell's surface, which allows them to communicate their message to proteins inside the cell, which in turn go to the nucleus and signal the expression of a particular gene. "The same signaling factors are used in many different contexts," Weiss noted. "It's the combination that counts."

Branching out all over

Darwin's notes

A page from Darwin's journals shows an early phylogenetic tree.

Combination is only one tactic. Another of life's short cuts is repetition. "Go home and look in the mirror," Weiss said. "Look at your teeth, your hair, your hands. We are built by repetitive patterning. I call this biological programming in installments—repeatedly making the same unit. This is found in all levels of life, from gene to cell to organ. Life is a profusion of modules."

Still another basic strategy for building complexity is branching, which Weiss called "probably the most powerful single metaphor of life." "It's a very simple, logical idea," he acknowledged. "Take one thing, split it into two, and they can then become different."

Darwin was big on branching, of course: How could he not be, when it popped up everywhere he looked? Not just in family
trees, but in real ones too, and in fingers and toes, plant roots and candelabras of coral. And the same forms show upinside organisms—in blood vessels, nerves, and the bronchioles of the lungs.

But according to Weiss, it's even more basic than that. "Multicellular organisms begin their lives organized as balls or tubes," he writes. "[They] become more complex through branching"—whether that means splitting off repeat units as in blood vessels and roots, or producing hierarchies, like the digestive organs that branch from the developing gut or the distinctive regions of the brain.

Branching, he continued, allows for yet another developmental gambit: asymmetry. Here a branch of undifferentiated cells is exposed to a quantity of signaling factor at one end which slowly diffuses to the other, the concentration growing less and less as the chemical spreads. These cells, because of the receptors on their membranes, detect the concentration outside, and have mechanisms in their genome that, depending on that concentration, will switch them into different functional behaviors by turning on different genes.

Vertebrates and insects both use this mechanism to turn quantities of signaling factors into qualities of structure, Weiss said—"different limb bones, or wing parts. The same system is used to produce the segmented bodies of insects." Although asymmetry may be less evident than symmetry in the mature organism, its role in development is significant.

Evo-Devo

Ken Weiss
James Collins

Ken Weiss

The fresh perspective of developmental biology offers some powerful new generalizations for understanding how life evolves."It's a lot simpler than having to have a specific gene for every structure, which is what we thought genetics was all about," Weiss said. "At the same time, we can't forget that evolution produces variation, among individuals within a species as well as among species. Development never comes out exactly the same from organism to organism."

He flashed a slide of a complicated flow chart, a dense nest of boxes and connecting lines depicting what is known about the regulation of a single trait—the formation of a single type of cell in a particular variety of sea urchin. "It shows a process made up of multiple gene interactions," Weiss said. "Each of these genes is a target for mutation. Each can accumulate variation. This is the opposite of simplicity, because mutations happen randomly.

"One of the great lessons of early-twentieth-century biology," he added, "was that there can be many genetic pathways to the same result. You being six feet tall and me being six feet tall will not be due to us sharing the exact same genotype, because no two people have the exact same genotype." At the species level, "teeth take similar form in mammals and in fish, but they are made in each case by independently evolved genes.

"Development and evolution are different faces of the same phenomena," Weiss concluded. "Evolution shows how diversity arises among organisms, development how diversity arises within organisms. They work together, but on different timescales: development a few weeks, evolution millions of years."

"With elegant simplicity and symmetry, history and function—evolution and development—are one," he writes. "They are facilitated by genes through the same modular, nested, branching logic of life."

Kenneth M.Weiss, Ph.D., is Evan Pugh professor of biological anthropology and genetics, and can be reached at kenweiss@psu.edu. This article is based on a talk given by Weiss as one of the 2006 Penn State Lectures on the Frontiers of Science. The annual
series is sponsored by the pharmaceutical company Pfizer, Inc., and Penn State's Eberly College of Science, and organized by Barbara K. Kennedy, coordinator of college relations.

Last Updated June 05, 2006