Pélisson Alain, Payen-Groschêne Geneviève, Terzian Christophe, Bucheton Alain
Institut de Génétique Humaine, CNRS, Montpellier, France.
Mol Biol Evol. 2007 Feb;24(2):498-504. doi: 10.1093/molbev/msl176. Epub 2006 Nov 21.
The flamenco (flam) locus, located at 20A1-3 in the centromeric heterochromatin of the Drosophila melanogaster X chromosome, is a major regulator of the gypsy/mdg4 endogenous retrovirus. In restrictive strains, functional flam alleles maintain gypsy proviruses in a repressed state. By contrast, in permissive strains, proviral amplification results from infection of the female germ line and subsequent insertions into the chromosomes of the progeny. A restrictive/permissive polymorphism prevails in natural and laboratory populations. This polymorphism was assumed to be maintained by the interplay of opposite selective forces; on one hand, the increase of genetic load caused by proviral insertions would favor restrictive flam alleles because they make flies resistant to these gypsy replicative transpositions and, on the other, a hypothetical resistance cost would select against such alleles in the absence of the retrovirus. However, the population cage data presented in this paper do not fit with this simple resistance cost hypothesis because restrictive alleles were not eliminated in the absence of functional gypsy proviruses; on the contrary, using 2 independent flam allelic pairs, the restrictive frequency rose to about 90% in every experimental population, whatever the pair of alleles and the allelic proportions in the initial inoculum. These data suggest that the flam polymorphism is maintained by some strong balancing selection, which would act either on flam itself, independently of the deleterious effect of gypsy, or on a hypothetical flanking gene, in linkage disequilibrium with flam. Alternatively, restrictive flam alleles might also be resistant to some other retroelements that would be still present in the cage populations, causing a positive selection for these alleles. Whatever selective forces that maintain high levels of restrictive alleles independently of gypsy, this unknown mechanism can set up an interesting kind of antiviral innate immunity, at the population level.
弗拉门戈（flam）基因座位于黑腹果蝇X染色体着丝粒异染色质区的20A1 - 3位置，是吉普赛/ mdg4内源性逆转录病毒的主要调节因子。在限制性品系中，功能性flam等位基因可使吉普赛原病毒保持在抑制状态。相比之下，在许可性品系中，原病毒扩增是由于雌性生殖系感染以及随后插入子代染色体所致。限制性/许可性多态性在自然种群和实验室种群中普遍存在。这种多态性被认为是由相反的选择压力相互作用维持的；一方面，原病毒插入导致的遗传负荷增加会有利于限制性flam等位基因，因为它们使果蝇对这些吉普赛复制性转座具有抗性，另一方面，在没有逆转录病毒的情况下，一种假设的抗性成本会选择淘汰此类等位基因。然而，本文所呈现的种群笼养数据并不符合这种简单的抗性成本假说，因为在没有功能性吉普赛原病毒的情况下，限制性等位基因并未被淘汰；相反，使用2个独立的flam等位基因对，无论初始接种物中的等位基因对和等位基因比例如何，每个实验种群中的限制性频率都上升到了约90%。这些数据表明，flam多态性是由某种强大的平衡选择维持的，这种选择可能作用于flam本身，独立于吉普赛的有害影响，或者作用于与flam处于连锁不平衡状态的一个假设的侧翼基因。或者，限制性flam等位基因也可能对仍存在于笼养种群中的其他一些逆转元件具有抗性，从而导致对这些等位基因的正向选择。无论维持高水平限制性等位基因独立于吉普赛的选择压力是什么，这种未知机制都可以在种群水平上建立一种有趣的抗病毒先天免疫。
