Global allele polymorphism indicates a high rate of allele genesis at a locus under balancing selection

When selection favours rare alleles over common ones (balancing selection in the form of negative frequency-dependent selection), a locus may maintain a large number of alleles, each at similar frequency. To better understand how allelic richness is generated and maintained at such loci, we assessed 201 sequences of the complementary sex determiner (csd) of the Asian honeybee (Apis cerana), sampled from across its range. Honeybees are haplodiploid; hemizygotes at csd develop as males and heterozygotes as females, while homozygosity is lethal. Thus, csd is under strong negative frequency-dependent selection because rare alleles are less likely to end up in the lethal homozygous form. We find that in A. cerana, as in other Apis, just a few amino acid differences between csd alleles in the hypervariable region are sufficient to trigger female development. We then show that while allelic lineages are spread across geographical regions, allelic differentiation is high between populations, with most csd alleles (86.3%) detected in only one sample location. Furthermore, nucleotide diversity in the hypervariable region indicates an excess of recently arisen alleles, possibly associated with population expansion across Asia since the last glacial maximum. Only the newly invasive populations of the Austral-Pacific share most of their csd alleles. In all, the geographic patterns of csd diversity in A. cerana indicate that high mutation rates and balancing selection act together to produce high rates of allele genesis and turnover at the honeybee sex locus, which in turn leads to its exceptionally high local and global polymorphism.Subject terms: Evolutionary genetics, Rare variants, Ecological genetics     

人血清白蛋白药物输运过程中的催化作用研究

血清白蛋白(HSA)是人体中重要的药物结合蛋白。药物在体内和血清白蛋白可逆性地结合可以增强药物的生物兼容性、延长药物半衰期并达到缓释的效果。但是研究发现药物和白蛋白的结合有时也会形成负面的影响。本文以能和活性氧反应的化学发光试剂FCLA为分子探针,研究分析了HSA和药物的相互作用及产生的影响。实验发现,HSA能通过与FCLA分子的结合,对FCLA的氧化产生类似于酶催化效果,通过降低氧化反应所需的活化能加速了探针的氧化过程。研究结果表明,HSA和某些药物的结合能够引起药物抗氧化能力或抗药物交叉反应能力的改变,因此在利用HSA携带药物时,需要考虑结合所导致的药物稳定性的降低。该研究有助于揭示体内的药物动力学问题,指导合理用药,同时对于进行药物分子设计、开发新药也具有重要的指导意义。