by
Abstract
At a conference on molecular strategies in biological evolution, researchers discussed how evolutionary strategies can evolve, making the process of evolution more efficient.
Is the ability to evolve and adapt a skill, learned by a genome as it moves through time and generations? Over 30 speakers from 10 nations explored the topic at a conference, Molecular Strategies in Biological Evolution, held June 27-29, 1998 in New York City and sponsored by the New York Academy of Sciences.
"The conventional explanation, that random changes accumulate one locus at a time, is unconvincing on both functional and probabilistic grounds because there is too much interconnectivity and too many degrees of mutational freedom," asserted James Shapiro of the University of Chicago.
Is this a rebuke of Darwin and Wallace? Not at all. The fittest strategies survive, along with the genomes that encode them. This overarching principle of evolution, which has been largely overlooked in popularized biology, makes more comprehensible both the tremendous diversity of life on earth and the great biochemical similarities between diverse organisms. Populations of organisms that can adapt more efficiently have a selective advantage. Jumps in efficiency - made possible by the discovery of new evolutionary strategies - could fuel apparent leaps in species abundance as each innovation evolves.
The very biochemical tools that we now use in laboratories are evolved to modulate local nucleotide variation, to rearrange genomic DNA sequences, and to acquire functional DNA sequences from the environment through horizontal gene transfer. Shapiro pointed out that we are not the first genetic engineers.
Nobelist Werner Arber, who cochaired the meeting, called "second order" the natural selection that leads to the emergence of an array of tools for generating diverse populations. Diversity among a genome's descendants gives a better chance that someone will survive in a challenging environment, or will be able to take advantage of a new opportunity [1].
Enzymes that repeatedly copy, move, and repair a nucleotide sequence affect the evolution of that sequence. Where the fidelity of a polymerase that copies DNA is high, the sequences will be preserved; where fidelity is low, the sequence will change. Thus, a balance between fidelity and exploration emerges though natural selection.
Much as a change in an organism's environment will induce a shifting array of metabolic enzymes, populations of organisms can regulate the balance between repair and exploration in their own genomes. An increased mutation rate may be deleterious - but it also can accelerate the rate at which populations adapt to a changing environment [2,3].
As emphasized by Richard Sinden of the Institute of Biosciences and Technology at Texas A&M, and Lynn Ripley of the University of Medicine and Dentistry of New Jersey - New Jersey Medical School the effect of the DNA sequence on mutation usually is overlooked. Far from the motionless double helix of textbook covers, "living" DNA is dynamic and structurally complex. In a given genome, certain genetic changes are, simply put, orders of magnitude more likely than other changes. Which genomes are favored to survive? Those for which the most probable changes are more likely to lead to new functions and less likely to destroy an important active site or structural scaffold.
Just as the use of interchangeable parts enabled the industrial revolution, the use of interchangeable genetic pieces has provided an efficient path to the evolution of functionally useful combinations of structures.
Ruth Hall of CSIRO/Molecular Science in Sydney provided examples of the strategy of sampling DNA from the environment. Integrons, genes, and groups of genes that move in and out of genomes like "cassettes", spread antibiotic resistance and pathogenicity, with tremendous significance for the emergence of new pathogens. Susanna Lewis of the University of Toronto suggested that transmission of a certain genetic sequence in a genome that already had the
ability to "edit" its DNA sequence in a certain way led to the genetically
innovative immune system of vertebrates, which uses a focused strategy of
shifting gene blocks as a way to explore genetic variation.
Duplication of genes and fragments of genes allows an organism to explore variation around a functional framework, while maintaining the original function. Combining functional modules (structural and functional motifs, genes, transport, binding, catalytic, and signaling domains, regulatory regions and signaling pathways) is a much more efficient way to explore useful variations of sequences than is random mutation. Edward Trifonov of the Weizmann Institute in Israel asserted that "evolution is translocation arid transposition, rather than point mutation." [4]
Ben Koop, of the Centre for Environmental Health at the University of Victoria, described the genome as a "dynamic playground" into which genes insert themselves. Shapiro argued that repetitive DNA elements set the "system architecture" of each species and that this, not the proteins, makes a species unique. Nina Fedoroff of Pennsylvania State University, Shigeru Iida of the National Institute for Basic Biology in Okazaki, Japan, and Shapiro all emphasized that transposable elements and other genetic repeats "modularize" the genome, representing segments that are most likely to rearrange and play active roles in genome reorganization and evolution. [5, 6] Implications range from genetic disease to cancer to antibiotic resistance to the patterns on morning glories.
Genetic diseases, from the genome's perspective, may be stumblings along the pathway of exploration.
It is reasonable to consider that mechanisms now used by the the immune system to respond to pathogens may be adapted from mechanisms that evolved in the germline enabling populations to respond to selective pressures more effectively than by selection among monotonous mutations. When we compare members of a gene family, certain sequence regions exhibit much higher variation than other regions. It is assumed that the different rates of change observed at different positions in a DNA sequence result solely for selection operating on the changed amino acids, one at a time. Isn't this assumption wrong, as it is wrong for the immune system?
If variation is intrinsically more probable in certain regions of a gene, we would expect even synonymous coding positions (i.e., changes that do not change the amino acid sequence) to have an increased rate of variation. Indeed, Giorgio Bernardi of the Institute Jacques Monod in Paris has observed a correlation between the rate of synonymous and nonsynonymous changes in many gene families [7].
Baldomero Olivera of the University of Utah raised the possibility that cone snails - possibly the largest living genus of marine invertebrates - have evolved a strategy for rapidly generating diverse toxins, which allows rapid adaptation to changes in prey, predators, and/or competitors. Olivera observes that this variation is focused on the toxin exon, which mutates at an apparent tenfold higher rather than other gene regions. It is hard to argue that these rapid sequence changes are generated by random point mutations throughout the gene, followed by selection of each altered amino acid, because there is a high rate of change at "synonymous" coding positions in the toxin exon.
An informative, and now accessible, area for analysis is the information content of nucleotide sequences within gene families. Just as individual organisms are at a selective advantage if their DNA encodes "better" amino acid sequences, populations of organisms with DNA sequences that allow exploration of useful sequence variation, such as those of the immune system, also would be at a selective advantage.
Jaws dropped when David Prescott of the University of Colorado at Boulder described an example of regulated, massive, and nonrandom alteration of DNA. The protozoan Oxytrichia fragments its germline chromosomes into thousands of pieces and then quickly reassembles a subset in a scrambled order [8].
How differently would we view genomes, Werner Arber asked, if we had been working on Oxytrichia for 30 years before someone looked at E. coli? And what would we understand that we do not yet understand, I wondered, about what happens to our own genome during meiosis?
As entire genomes are sequenced, our blindfolds are removed. As we perceive genomic strategies, will we join David Thaler of Rockefeller University in attributing "intelligence" to genomes? Perhaps we will. After all, how did we get to be so smart?
Lynn Caporale, who organized and cochaired the conference, is an independent researcher who works as a consultant to the pharmaceutical and biotech industries.
Andrzej Krauze is an illustrator, poster maker, cartoonist, and painter who illustrates regularly for HMS Beagle, The Guardian, The Sunday Telegraph, Bookseller, and New Statesman.
Optimum Mutation Rates in Evolution and Disease - HMS Beagle's Cutting Edge debate discusses mutational mechanisms in both dividing and nondividing cells, and how this relates to our understanding of both evolution and disease.
A New Passion for Evo-Devo - an HMS Beagle Meeting Brief describing the Fifth Annual Meeting of the Society for Molecular Biology and Evolution.
Some Published Works on Biochemical Evolution - a well-organized list of links to PubMed abstracts for papers on the evolution of biochemical systems and structures.
Molecular Evolution - an introduction to several concepts involved in the study of evolution at the level of DNA, this site is a part of the Lecture Notes series from Brown University's Evolutionary Biology class.
P Elements in Drosophila - a detailed online review of fruit-fly transposable elements. Maintained by William Engels of the University of Wisconsin at Madison.
The Mitochondrial Genome of Trypanosomes: Research in the Simpson Laboratory - if you still think of nucleic acids as static sequences, take a look at the creativity possible in nucleic acids highlighted by Larry Simpson's description of massive editing of RNA, and the world of cryptogenes.
EBI Sander Group, GenProTECE: E. coli Genome and Proteome Database, Laboratory for DNA Data Analysis Center for Information Biology - sites showing the effect of DNA sequences on mutation.
Schimenti Lab - an interest in evolution mandates a look at the germline of eukaryotes. The first step to analyzing what happens in mammalian germ lines was presented by John Schimenti of the Jackson Lab.