Ernst Mayr's theory illustrated in genetic epidemiology studies

Feb 19 2006

The late, famed evolutionary biologist Ernst Mayr's theory of genetic revolution , introduced in 1954, remains controversial to this day and has many detractors.

Mayr believed that genes interacted with one another, and that this genetic interaction in turn led to an interaction of natural selection with genetic drift that could cause genetic revolution - new directions of evolutionary change.

Detractors of the theory object to what they consider the random nature of genetic drift.

But an evolutionary and population biologist at Washington University in St. Louis says that Mayr's theory has been illustrated nicely in recent years in human genetic epidemiology and population biology studies.

Alan R. Templeton, Ph.D., Washington University professor of biology in Arts & Sciences, said that there is an extensive documentation of genetic interaction over the past few years including his own genetic epidemiology studies of coronary artery disease (CAD).

"These recent results really show that Mayr's ideas were correct," said Templeton. "His theory has been empirically supported very well."

But first, the background. Mayr thought that founder events were very important in the origins of new species. These occur when a very small population of a species gets established in a new area. Because the population is very small, there is a lot of genetic randomness, and there is only a subset of the genetic variation of the ancestral population, and the frequencies of different kinds of genes can be changed dramatically.

Mayr also believed that there is lots of interaction between genes, so that when the frequency of one gene changes randomly, that causes a different suite of interactions to occur so that natural selection will drive the founder population in a different direction. He saw a very strong interaction between natural selection and random forces in a founder population.

"Mayr felt that the interaction of selection and what we call genetic drift could cause what he called a genetic revolution, a rather radical adaptive change that would be unlikely to happen if you had just natural selection in a large population alone," Templeton said. "It's kind of like you stirred the pot at random, but then it goes off in a new direction due to natural selection.

So, that was a very controversial idea when it was introduced. I corresponded with Mayr for 25 years, and he considered it to be one of his very best ideas."

Templeton said that there are still a lot of biologists who don't like the idea of genetic drift, but he thinks that they miss two very important concepts of Mayr's argument. One is that genes interact with one another extensively, and that with the establishment of an interaction system, it's inevitable that once frequencies are changed, the direction of natural selection changes.

"We now know from my CAD work and other genetic epidemiology studies that we find these kinds of genetic interactions all over the place, so that modern molecular biology has confirmed Mayr's idea of genetic architecture," Templeton said. "Given that you have this interaction it's inevitable that a random process like drift will interact with natural selection strongly to spark new directions of evolutionary change."

The other thing detractors object to is the random aspect of evolutionary change.

"Those uncomfortable with Mayr's theory don't take into account that under his model, it's the interaction of the random that forces the natural selection that creates the evolutionary change," Templeton said. "Although the initial founder effect is somewhat random, the changes that emerge out of it are highly non-random and are very much directed by natural selection and are adaptive.

"It's incorrect to portray genetic revolution as just a random speciation model. It's a process that is very strongly driven by natural selection, but this adaptive process can go in directions that can't be predicted just by selection alone because a random force puts a new direction into play - that's where the genetic revolution comes from."

Templeton spoke Feb. 18 at the annual meeting of the American Association for the Advancement science, held Feb. 16-20 in St. Louis. He dedicated his talk to the late Ernst Mayr and the late Hampton Carson, another famed biologist who was at Washington University from 1944-70 and was an important mentor of Templeton's. Templeton said that Carson's work on founder events with an Hawaiian Drosophila species contributed greatly to the refinement of May's concept of genetic revolution.

Templeton said that his CAD studies in human founder populations reveal interactions between two important genes involved in high cholesterol, the Apolipoprotein E (APOE) gene and the Low density lipoprotein receptor (LDLR) gene. Interestingly, it has been found that the protein products of these genes physically interact. Both play a role in high cholesterol that can lead to CAD, but in most human populations the APOE component is very rare and the LDLR component is very common.

Because rare factors tend to be the limiting factors in an interaction system, strong genetic effects are observed only at APOE - the rare component - and not at LDLR - the common component. However, simply by altering the frequencies of the interacting genes, the apparent importance of these two genes in influencing cholesterol levels can be totally reversed. Such alterations, Templeton said, are the fundamental basis of genetic revolution.

A school of biologists who goes back to the English biologist R. A. Fisher believes that genes alone inherently are major or minor in terms of effects on traits. A school following the 1920s biologist Sewal Wright believes there is no such thing as a major or minor gene except in the context of another population. Templeton is in the Wright camp.

"As soon as you have interactions between genes and then change the frequencies of these genes through some random factor, you're going to have a tremendous shift in where natural selection is directed in a genetic sense," he said. "This is the underlying basis of genetic revolution. We have documented that a gene major in one population is minor in another. This is a very real phenomenon that documents Mayr's point of view."

Templeton said that the Fisher camp views major and minor genes as if they are the properties of the single gene itself. His, Wright's and Mayr's view is that major and minor are properties of an interactive genetic system, and, depending on the frequencies of the interacting factors, some genes seem to play a larger role than others at any given time.

"The real causation of the trait is at the interaction level and not the single gene level, and therefore if you change just the frequency of the gene you'll change what's major and what's minor, and that's another way of saying you're changing how natural selection acts on the system," he said.