Further statistical analysis for genome-wide expression evolution in primate brain/liver/fibroblast tissue
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Further statistical analysis for genomewide expression evolution in primate brain/liver/fibroblast tissues Jianying Gu§ and Xun Gu* Department of Genetics, Developmental and Cellular Biology (GDCB), Iowa State University, Ames, IA 50011, USA § Current address: Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637, USA *Correspondence to: Tel: þ1 515 294 8075; Fax: þ1 515 294 8457; E-mail: [email protected] Date received (in revised form): 18th December 2003
Abstract
In spite of only a 1–2 per cent genomic DNA sequence difference, humans and chimpanzees differ considerably in behaviour and cognition. Affymetrix microarray technology provides a novel approach to addressing a long-term debate on whether the difference between humans and chimpanzees results from the alteration of gene expressions. Here, we used several statistical methods (distance method, two-sample t-tests, regularised t-tests, ANOVA and bootstrapping) to detect the differential expression pattern between humans and great apes. Our analysis shows that the pattern we observed before is robust against various statistical methods; that is, the pronounced expression changes occurred on the human lineage after the split from chimpanzees, and that the dramatic brain expression alterations in humans may be mainly driven by a set of genes with increased expression (up-regulated) rather than decreased expression (down-regulated). Keywords: microarray, Affymetrix, differential expression, human evolution
Introduction Comparison of the human genome with closely related species, as well as distantly related species, has provided a better understanding of human evolution. Well before the era of modern molecular biology, great apes (chimpanzees, pygmy chimpanzees and gorillas) had already been recognised as human’s closest relatives. The divergence time between human and chimpanzee is estimated to be only 4.6 – 6.2 million years ago, based on the sequences of autosomal intergenic nonrepetitive DNA in human, chimpanzee, gorilla and orangutan.1 Humans have already evolved considerable differences from chimpanzees, however, in morphological appearance, behaviour, language and cognition, as well as in disease susceptibility (eg susceptibility to human immunodeficiency virus). Only about a 1.2 per cent difference,2 – 4 however, or up to 5 per cent difference including insertions and deletions,5 appears in their genomic DNA sequences. This striking observation raises an interesting question concerning the genetic basis for the difference between humans and chimpanzees. The long-term hypothesis of gene expression alteration remains attractive but still calls for hard evidence.2 Recently, Enard et al.6 studied the gene expression patterns across several primate species by using microarray technol-
ogies. Their analysis suggested that it is the brain rather than the liver that has a dramatic expression change in the human lineage compared with that in the chimpanzee lineage. The original work did not include an appropriate statistical assessment,
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