Nielsen Kirsten, Marra Robert E, Hagen Ferry, Boekhout Teun, Mitchell Thomas G, Cox Gary M, Heitman Joseph
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Genetics. 2005 Nov;171(3):975-83. doi: 10.1534/genetics.105.045039. Epub 2005 Jun 18.
The study of quantitative traits provides a window on the interactions between multiple unlinked genetic loci. The interaction between hosts and pathogenic microbes, such as fungi, involves aspects of quantitative genetics for both partners in this dynamic equilibrium. One important pathogenic fungus is Cryptococcus neoformans, a basidiomycete yeast that can infect the human brain and whose mating system has two mating type alleles, a and alpha. The alpha mating-type allele has previously been linked to increased virulence potential. Here congenic C. neoformans strains were generated in the two well-characterized genetic backgrounds B3501alpha and NIH433a to examine the potential influence of genes outside of the mating-type locus on the virulence potential of mating type. The congenic nature of these new strain pairs was established by karyotyping, amplified fragment length polymorphism genotyping, and whole-genome molecular allele mapping (congenicity mapping). Virulence studies revealed that virulence was equivalent between the B3501 a and alpha congenic strains but the alpha strain was more virulent than its a counterpart in the NIH433 genetic background. These results demonstrate that genomic regions outside the mating type locus contribute to differences in virulence between a and alpha cells. The congenic strains described here provide a foundation upon which to elucidate at genetic and molecular levels how mating-type and other unlinked loci interact to enable microbial pathogenesis.
对数量性状的研究为了解多个非连锁基因座之间的相互作用提供了一个窗口。宿主与致病微生物（如真菌）之间的相互作用涉及到这种动态平衡中双方的数量遗传学方面。一种重要的致病真菌是新生隐球菌，它是一种担子菌酵母，可感染人脑，其交配系统有两种交配型等位基因，a和α。此前已发现α交配型等位基因与毒力增加有关。在此，我们在两个特征明确的遗传背景B3501α和NIH433a中构建了同基因新生隐球菌菌株，以研究交配型基因座以外的基因对交配型毒力潜力的潜在影响。通过核型分析、扩增片段长度多态性基因分型和全基因组分子等位基因定位（同基因定位）确定了这些新菌株对的同基因性质。毒力研究表明，B3501 a和α同基因菌株之间的毒力相当，但在NIH433遗传背景中，α菌株比其a对应菌株的毒力更强。这些结果表明，交配型基因座以外的基因组区域导致了a细胞和α细胞之间毒力的差异。本文所述的同基因菌株为在遗传和分子水平上阐明交配型和其他非连锁基因座如何相互作用以引发微生物致病机制奠定了基础。
