Genetics of Hybrid Sterility in Drosophila

物种的一个共同特征是它们在杂交时产生不育的杂交种。然而，杂交不育的遗传原因尚不清楚，因为这些相同的基因在两个亲本物种中正常起育性作用。本文提出了实验来评估基因表达中断在果蝇（果蝇）物种杂交不育中的作用。首先，将使用高通量微阵列和其他技术对杂交和亲本物种进行调查，以确定数千个个体基因的表达。其次，将测试亲本种和杂交种之间表达的差异与杂交种不育的关系。第三，利用遗传作图技术，定位导致杂交种基因表达中断的遗传差异。在这一点上，引起这些破坏的候选基因可能会通过对果蝇生育能力进行的广泛基因研究的结果来确定。这项提议的工作具有很强的进化和医学意义。就进化生物学而言，杂交不育是物种差异的“标志”。了解导致不育的遗传相互作用的本质，可以直接了解是什么使一个物种与另一个物种不同，因此，可以解释新物种的起源过程。从医学角度来看，估计有5%的成年男性患有由基因决定的不育症。许多与人类不育有关的基因与果蝇的基因相似，这两个物种的生育能力具有相当的遗传复杂性。初步研究发现，在不育的果蝇杂交雄性中，有19个与人类基因序列高度相似的基因失活，其中包括许多与精子形成有关的基因。对这种实验室生物的持续研究可以帮助识别其他基因，这些基因在人类中被破坏可能导致不孕。

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.