Dr. Michael D. Purugganan, associate professor, and Dr. Kenneth M. Olsen, postdoctoral fellow, both of the Department of Genetics at NC State, joined colleagues from other universities to demonstrate two key results in "The Cost of Inbreeding in Arabidopsis," published in the April 4, 2002 issue of Nature.
According to Purugganan, as the researchers compared amino acid replacement among species of the mustard weed Arabidopsis with those among species of the fruit fly Drosophila, they found evidence for mostly beneficial gene substitutions in the flies, but mostly detrimental substitutions in the weed. "We attribute this difference to the Arabidopsis mating system of partial self-fertilization," he said, "which corroborates a prediction in genetics theory that species with a high frequency of inbreeding will be less efficient in eliminating deleterious mutations."
Purugganan and Olsen worked with Dr. Daniel L. Harti and Dr. Carlos D. Bustamante of Harvard University; Dr. Stanley A. Sawyer of Washington University; and Dr. Rasmus Nielsen of Cornell University in developing the findings. The research at NC State is funded by an interdisciplinary grant from the National Science Foundation's Integrated Research Challenges in Environmental Biology (IRCEB) program. Purugganan is also the recipient of an Alfred P. Sloan Foundation Young Investigator award, which helped fund part of the research.
Inbreeding in flies does not show the same detriment found in the mustard weed because, Purugganan said, "the way flies operate is that they mate with each other in a more-or-less random fashion, and Arabidopsis naturally mates with itself 99 percent of the time - its pollen will fertilize its own stigma." Flies forced to inbreed for thousands of generations might show the deleterious mutations found in the mustard weed. "In humans, for example" said Purugganan, "groups in small isolated populations may build up greater amounts of 'bad' mutations and reduce the 'genetic health' of the population. This is also one reason why it is important to increase population sizes of endangered species - small populations may lead to build-up of bad mutations, and make it more difficult to save these species."
In addition to verifying, at a molecular level, a prediction of evolutionary theory, said Olsen, their research has a second key result. "The method outlined in the paper provides genomics scientists with new methods to look at the effect of selection among different genes in the genome," he said. "This may lead to a greater understanding of how genomes evolve through time."
Editor's note: Included below is the abstract and other pertinent information about the article published in Nature. To see this and related articles, visit www.nature.com.
"The Cost of Inbreeding in Arabidopsis"
Authors: Michael D. Purugganan, Kenneth M. Olsen, North Carolina State University; Daniel L. Harti, Carlos D. Bustamente, Harvard University; Stanley A. Sawyer, Washington University; Rasmus Nielsen, Cornell University. Published: April 4, 2002, in Nature
Abstract: Population geneticists have long sought to estimate the distribution of selection intensities among genes of diverse function across the genome. Only recently have DNA sequencing and analytical techniques converged to make this possible. Important advances have come from comparing genetic variation within species (polymorphism) to fixed differences between species (divergence) (1,2). These approaches have been used to examine individual genes for evidence of selection. Here we use the fact that the species divergence time allows combination of data across genes. In a comparison of amino acid replacements among species of the mustard weed Arabidopsis with those among species of the fruit fly Drosophila, we find evidence for predominantly beneficial gene substitutions in Drosophila but predominantly detrimental substitutions in Arabidopsis. We attribute this difference to the Arabidopsis mating system of partial self-fertilization, which corroborates a prediction of population genetics theory (3-6) that species with a high frequency of inbreeding will be less efficient in eliminating deleterious mutations owing to their reduced effective population size. We conclude from figures 2 and 3 that the average amino acid replacement that is polymorphic or fixed in Drosophila is beneficial, whereas the average amino acid replacement that is polymorphic or fixed in Arabidopsis is slightly deleterious. This result is consistent with a recent decrease in effective population size in A. thaliana, which is predicted (3-6) to result from its mode of reproduction largely by self-fertilization (15). A lyrata reproduces by outcrossing (16) and phylogenetic evidence indicates that partial selfing is a derived trait (17).
Beyond the present application, hierarchical Bayesian analysis affords a theoretical framework for a science of evolutionary genomics. In principle it could discriminate among the evolutionary forces that affect proteins of diverse function, identifying effects specific to sex, tissue and developmental stage of expression, cellular location, three-dimensional structure, and mechanism of action. The analysis could also sort out the evolutionary forces affecting upstream, downstream, intropic and intergenic regions of genes. Even in this era of high-throughput genomic sequencing, the acquisition of genome-wide polymorphism-divergence data presents a formidable challenge.
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