Linkage-disequilibrium approach for detecting genetic inter actions between extracellular and membrane molecules

点击翻译按钮获取中文摘要

Many quantitative characters including complex genetic diseases are likely subject to truncation selection or other forms of multi-locus selection; however, direct measure of selection in natural populations remains difficult Multi-locus selection with epistasis can generate linkage disequilibrium from which we can infer the pattern and degree of selection and then functional connections of genes. Based on this idea, we studied polymorphisms in natural populations of D. melanogaster and obtained the following findings: 1) We found a large number of inter-locus nonrandom associations between polymorphisms in Drosophila chemoreceptor genes and a significant excess of haplotypes composed of one frequent and one less common allele in replacement but not silent polymorphisms. These results implied that multi-locus selection plays a significant role in shaping within-species variation, particularly to reduce frequencies of replacement polymorphisms that are slightly deleterious in combination with other polymorphisms. 2) We developed a new test to detect viability selection over a single generation. In this test, one specific type of chromosomes is chosen as a reference, while all other chromosomes are designated as focal. The test compares measures of variation between two groups of focal chromosomes: those found in reference/focal heterozygous individuals, and those found in focal/focal homozygotes. Currently acting selection can cause differences in some measures of variation. We applied this test to typing data for In (2L)t inversion polymorphism and X-linked chemoreceptor genes in Drosophila melanogaster populations and found evidence for selection. This new test and population genetics measures for linkage disequilibrium shed light on how often strong selection is operating in extant populations and serve to identify functional connections of genes.