Organismal complexity, cell differentiation and gene expression: human over mouse

Abstract

We present a molecular and cellular phenomenon underlying the intriguing increase in phenotypic organizational complexity. For the same set of human-mouse orthologous genes (11 534 gene pairs) and homologous tissues (32 tissue pairs), human shows a greater fraction of tissue-specific genes and a greater ratio of the total expression of tissue-specific genes to housekeeping genes in each studied tissue, which suggests a generally higher level of evolutionary cell differentiation (specialization). This phenomenon is spectacularly more pronounced in those human tissues that are more directly involved in the increase of complexity, longevity and body size (i.e. it is reflected on the organismal level as well). Genes with a change in expression breadth show a greater human-mouse divergence of promoter regions and encoded proteins (i.e. the functional genomics data are supported by the structural analysis). Human also shows the higher expression of translation machinery. The upstream untranslated regions (5'UTRs) of human mRNAs are longer than mouse 5'UTRs (even after correction for the difference in genome sizes) and contain more uAUG codons, which suggest a more complex regulation at the translational level in human cells (and agrees well with the augmented cell specialization).

Figure 1.

The ratio of the total expression of tissue-specific genes to the total expression of housekeeping genes in human (blue squares), mouse (green diamonds) and the ratio of the former to the latter, i.e. the human/mouse ratio of both ratios (red circles) in 32 homologous tissues (based on 11534 orthologous genes). Note that all blue squares are higher than the corresponding green diamonds, and, as a consequence, all red circles are above unity. (Symbol size is greater than error. Red dotted line indicates median for all 32 tissues. Tissue-specific genes are those expressed in <32 tissues; housekeeping genes are those expressed in all 32 tissues, according to cutoff ‘median expression’ (as recommended in refs 13–15). If the Affymetrix calls were used, the picture was qualitatively the same with a similar ranking of the tissues.)