Molecular Analysis of Naturally Occurring Copia Variation

小行星9307220 天然复制变异的分子分析 (John F. McDonald，P.I.）% 越来越多的证据表明，逆转录病毒和逆转录病毒样转座因子是高等真核生物（包括人类）突变的主要来源。 这一事实的后果延伸到广泛的生物学科，从医学到进化遗传学。 虽然我们现在对逆转录病毒样因子如何改变染色体基因表达的机制有了很多了解，但对逆转录病毒样因子如何在物种内和物种间维持和传播却知之甚少或一无所知。 此外，关于通常是非适应性的逆转录病毒元件插入突变如何仍然可以增加频率并最终变得“固定”（即，随着时间的推移，在某些物种中的频率达到1.00）。 一种可能性是，能够抑制与逆转录病毒插入变体相关的突变表型的宿主染色体基因存在于自然群体中，并通过保护它们免受自然选择而起到窝藏插入变体的作用。 McDonald博士假设，由于“奠基者事件”或其他类似的强迫近亲繁殖效应，插入变异可能会周期性地增加频率。 在接下来的三年里，McDonald博士将研究copia逆转录病毒样因子在果蝇自然种群中维持和传播的机制。 果蝇是这些研究的理想系统，因为逆转录病毒元件在这种生物体中被很好地理解，并且元件频率和突变效应可以容易地监测。 McDonald博士将致力于鉴定能够反式调节逆转录病毒成分的宿主基因，并研究它们在一些果蝇物种中的频率和作用模式。 将分析从一些果蝇种群和物种中分离的copia元件的DNA序列，以确定可能影响元件活性的结构差异在自然种群中是否可变。 McDonald博士将通过将相同的copia LTR报告基因构建体引入几种菌株和物种中并监测LTR介导的表达的效果来寻找反式调节作用。 研究结果将有助于阐明逆转录病毒成分在所有高等真核生物的自然种群和物种中维持和传播的决定因素。 ***

9307220 McDonald Molecular Analysis of Naturally Occurring copia Variations (John F. McDonald, P.I.)%%% There is an ever growing body of evidence that retroviruses and retroviral-like transposable elements are a major source of mutation in higher eukaryotes including humans. The ramifications of this fact extend to a broad range of biological disciplines ranging from medicine to evolutionary genetics. Although we now know a great deal on the mechanisms of how retroviral-like elements alter the expression of chromosomal genes, little or nothing is known concerning how retroviral elements are maintained and spread within and between species. In addition, it remains a mystery as to how retroviral elements insertion mutations which are usually non-adaptive can nevertheless increase in frequency and eventually become "fixed" (i.e., attain a frequency of 1.00) in some species over time. One possibility is that host chromosomal genes capable of suppressing the mutant phenotype associated with retroviral insertion variants are present in natural populations and serve to harbor insertion variants by shielding them from natural selection. Dr. McDonald hypothesizes that insertion variants may periodically increase in frequency due to "founder events" or other such forced inbreeding effects.%%% Over the next three years Dr. McDonald will study the mechanisms by which the copia retroviral-like element is maintained and spread through natural populations of Drosophila. Drosophila is an ideal system for these studies because retroviral elements are well understood in this organism and element frequency and mutational effects can be easily monitored. Dr. McDonald will be concentrating on identifying host genes capable of trans-regulating retroviral elements and studying their frequency and mode of action in a number of Drosophila species. The DNA sequence of copia elements isolated from a number of Drosophila populations and species will be analyzed t o determine if structural differences which might affect element activity are variable in natural populations. Dr. McDonald will search for transregulatory effects by introducing the same copia LTR-reporter gene construct into several strains and species and monitoring the effect of LTR mediated expression. Results will shed light on the factors determining the maintenance and spread of retroviral elements in natural populations and species of all higher eukaryotes. ***