Genetics of Hybrid Sterility in Drosophila

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One common feature of species is that they produce sterile hybrids when intercrossed. However, the genetic causes for hybrid sterility are poorly understood, as these same genes function normally for fertility in the two parent species. Experiments are proposed herein to evaluate the role of disruptions in gene expression in causing hybrid sterility in Drosophila (fruit fly) species. First, hybrids and parent species will be surveyed for the expression of thousands of individual genes using high-throughput microarrays and confirmation with other techniques. Second, differences in expression between parent species and hybrids will be tested for their association with hybrid sterility. Third, using genetic mapping techniques, the genetic differences leading to disruptions in gene expression in hybrids will be localized. At that point, candidate genes causing these disruptions may be identified using the results of the extensive genetic research that has been performed on fertility in Drosophila.The proposed work has strong evolutionary and medical implications. With respect to evolutionary biology, hybrid sterility is a "hallmark" of species differences. Understanding the nature of genetic interactions causing sterility gives direct insights into what makes one species different from another, and hence, can explain the process of the origin of new species. From a medical perspective, an estimated 5% of human male adults suffer from sterility that is genetically determined. Many genes implicated in human infertility have similarity to Drosophila genes, and fertility in the two species is of comparable genetic complexity. Preliminary work identified 19 genes as inactive in sterile Drosophila hybrid males that have high sequence similarity to human genes, including many involved in sperm formation. Continued application of research in this laboratory organism can help identify other genes whose disruptions in humans may cause infertility.