Lipovich Leonard, Hou Zhuo-Cheng, Jia Hui, Sinkler Christopher, McGowen Michael, Sterner Kirstin N, Weckle Amy, Sugalski Amara B, Pipes Lenore, Gatti Domenico L, Mason Christopher E, Sherwood Chet C, Hof Patrick R, Kuzawa Christopher W, Grossman Lawrence I, Goodman Morris, Wildman Derek E
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, 48201.
Department of Neurology, School of Medicine, Wayne State University, Detroit, Michigan, 48201.
J Comp Neurol. 2016 Feb 1;524(2):288-308. doi: 10.1002/cne.23843. Epub 2015 Aug 20.
The human brain and human cognitive abilities are strikingly different from those of other great apes despite relatively modest genome sequence divergence. However, little is presently known about the interspecies divergence in gene structure and transcription that might contribute to these phenotypic differences. To date, most comparative studies of gene structure in the brain have examined humans, chimpanzees, and macaque monkeys. To add to this body of knowledge, we analyze here the brain transcriptome of the western lowland gorilla (Gorilla gorilla gorilla), an African great ape species that is phylogenetically closely related to humans, but with a brain that is approximately one-third the size. Manual transcriptome curation from a sample of the planum temporale region of the neocortex revealed 12 protein-coding genes and one noncoding-RNA gene with exons in the gorilla unmatched by public transcriptome data from the orthologous human loci. These interspecies gene structure differences accounted for a total of 134 amino acids in proteins found in the gorilla that were absent from protein products of the orthologous human genes. Proteins varying in structure between human and gorilla were involved in immunity and energy metabolism, suggesting their relevance to phenotypic differences. This gorilla neocortical transcriptome comprises an empirical, not homology- or prediction-driven, resource for orthologous gene comparisons between human and gorilla. These findings provide a unique repository of the sequences and structures of thousands of genes transcribed in the gorilla brain, pointing to candidate genes that may contribute to the traits distinguishing humans from other closely related great apes.
尽管人类与其他大型猿类的基因组序列差异相对较小,但人类大脑和认知能力却与它们有着显著不同。然而,目前对于可能导致这些表型差异的基因结构和转录的种间差异了解甚少。迄今为止,大多数关于大脑基因结构的比较研究都集中在人类、黑猩猩和猕猴身上。为了增加这方面的知识,我们在此分析了西部低地大猩猩(Gorilla gorilla gorilla)的大脑转录组,这是一种非洲大型猿类,在系统发育上与人类密切相关,但其大脑大小约为人类的三分之一。通过对新皮质颞平面区域样本进行手动转录组筛选,发现了12个蛋白质编码基因和1个非编码RNA基因,其外显子在大猩猩中与直系同源人类基因座的公共转录组数据不匹配。这些种间基因结构差异总共导致大猩猩中发现的蛋白质中有134个氨基酸在直系同源人类基因的蛋白质产物中不存在。人类和大猩猩之间结构不同的蛋白质涉及免疫和能量代谢,表明它们与表型差异相关。这个大猩猩新皮质转录组为人类和大猩猩之间的直系同源基因比较提供了一个基于经验而非同源性或预测驱动的资源。这些发现提供了大猩猩大脑中数千个转录基因的序列和结构的独特库,指出了可能导致人类与其他密切相关大型猿类不同性状的候选基因。