Wayne M L, Pan Y-J, Nuzhdin S V, McIntyre L M
Department of Zoology, University of Florida, Gainesville, Florida 32611, USA.
Genetics. 2004 Nov;168(3):1413-20. doi: 10.1534/genetics.104.030973.
Understanding how genetic variation is maintained begins with a comprehensive description of what types of genetic variation exist, the extent and magnitude of the variation, and patterns discernable in that variation. However, such studies have focused primarily on DNA sequence data and have ignored genetic variation at other hierarchical levels of genetic information. Microarray technology permits an examination of genetic variation at the level of mRNA abundance. Utilizing a round-robin design, we present a quantitative description of variation in mRNA abundance in terms of GCA (general combining ability or additive variance). We test whether genes significant for GCA are randomly distributed across chromosomes and use a nonparametric approach to demonstrate that the magnitude of the variation is not random for GCA. We find that there is a paucity of genes significant for GCA on the X relative to the autosomes. The overall magnitude of the effects for GCA on the X tends to be lower than that on the autosomes and is contributed by rare alleles of larger effect. Due to male hemizygosity, GCA for X-linked phenotypes must be due to trans-acting factors, while GCA for autosomal phenotypes may be due to cis- or trans-acting factors. The contrast in the amount of variation between the X and the autosomes suggests that both cis and trans factors contribute to variation for expression in D. simulans with the preponderance of effects being trans. This nonrandom patterning of genetic variation in gene expression data with respect to chromosomal context may be due to hemizygosity in the male.
理解遗传变异是如何维持的,首先要全面描述存在哪些类型的遗传变异、变异的范围和程度,以及在该变异中可辨别的模式。然而,此类研究主要集中在DNA序列数据上,而忽略了遗传信息其他层次水平上的遗传变异。微阵列技术允许在mRNA丰度水平上检测遗传变异。利用循环设计,我们从一般配合力(GCA,即加性方差)的角度对mRNA丰度的变异进行了定量描述。我们测试了对GCA有显著影响的基因是否随机分布在染色体上,并使用非参数方法证明变异程度对于GCA而言并非随机的。我们发现,相对于常染色体,X染色体上对GCA有显著影响的基因较少。X染色体上GCA效应的总体大小往往低于常染色体上的,并且是由效应较大的稀有等位基因造成的。由于雄性的半合子性,X连锁表型的GCA必定归因于反式作用因子,而常染色体表型的GCA可能归因于顺式或反式作用因子。X染色体和常染色体之间变异量的差异表明,顺式和反式因子都对拟暗果蝇(D. simulans)的表达变异有贡献,其中反式作用占主导。基因表达数据中遗传变异相对于染色体背景的这种非随机模式可能是由于雄性的半合子性。