Most widely expressed genes are also highly expressed. Based on high or wide expression, different models were proposed to explain the small sizes of highly/widely expressed genes. We found that housekeeping genes are not more compact than narrowly expressed genes with similar expression levels, but compactness and expression level are correlated in housekeeping genes (except that highly expressed Arabidopsis HK genes have longer intron length). Meanwhile, we found evidence that genes with high functional/regulatory complexity do not have longer introns and longer proteins. The genome design hypothesis is thus not supported. Furthermore, we found that housekeeping genes are not more compact than the narrowly expressed somatic genes with similar average expression levels. Because housekeeping genes are expected to have much higher germline expression levels than narrowly expressed somatic genes, transcription-associated deletion bias is not supported. Selection of the compactness of highly expressed genes for economy is supported. (c) 2007 Elsevier Inc. All rights reserved.