Question

You are investing the function of gene X in human cells. You have two different cell types in culture. One is the hepatic cells isolated from an individual. The other is the hematopoietic stem cells isolated from the same individual. Upon quantitative reverse transcriptase (RT)-PCR and Western blot analysis, you discovered that hepatic cells express higher level of gene X than hematopoietic stem cells do. Another difference you noticed were that protein X (produced from gene X) from hematopoietic stem cells is 54 kDa in size but it is 68 kDa from hepatic cells. Explain what are potential biological processes that contributed on the differential gene expression levels and different sizes of the same gene.

Answer 1

Gene expression is of critical importance to many fundamental biological processes, including species divergence (1), protein evolution (2), and adaptation to microenvironment (3). In multicellular organisms, the complexity of gene expression is often summarized by two measures: first, how many transcripts are generated per locus (referred to as ‘gene expression level’) and second, how broadly each transcript is found in different tissues (referred to as ‘gene expression breadth’). Together, levels and breadths of gene expression shape the diversity of organismal transcriptomes and eventually facilitate the development and maintenance of complex biological systems.

What factors determine the levels and breadths of gene expression? While the importance of locus-specific motifs in the regulation of gene expression is highly recognized, it is becoming clear that some features of gene sequences themselves (referred to as ‘genomic traits’ henceforth) are associated with the levels and breadths of gene expression. For example, the relationship between gene compactness and gene expression has been explored by several groups (4–6). Some studies proposed positive correlations between G+C contents and expression levels and breadths (7). Gene expression is also correlated with evolutionary rates. Highly expressed genes are associated with slower evolutionary rates in yeast and mammals (2,8–10). Evolutionary rates are also negatively associated with gene expression breadths (11–13).

However, it is important to take into account the fact that many of the genomic traits discussed above are correlated with each other. For example, G+C contents are correlated with several other genomic features in some taxa (14). The observed correlations between G+C contents and the measures of gene expression could have been confounded by the relations between G+C contents and other genomic traits such as gene compactness. One of the goals of this work is to generate a statistical framework in which we can jointly evaluate the effect of each genomic trait while controlling for the effects of other, often highly correlated, genomic traits.

Another complicating issue is the fact that the expression level and the expression breath are highly correlated with each other (discussed subsequently). This makes it especially difficult to test whether a specific genomic trait influences one aspect of gene expression more strongly than the other. In this paper, we overcome this difficulty by developing a method to utilize this correlation. We provide a novel statistical technique to quantitatively compare an individual genomic trait's influence on the gene expression level with that on the gene expression breadth (see Materials and Methods for more details).

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) or small nuclear RNA (snRNA) genes, the product is a functional RNA. Gene expression is summarized in the Central Dogma first formulated by Francis Crick in 1958,[1] further developed in his 1970 article,[2] and expanded by the subsequent discoveries of reverse transcription[3][4][5] and RNA replication.[6]

The process of gene expression is used by all known life—eukaryotes (including multicellular organisms), prokaryotes (bacteria and archaea), and utilized by viruses—to generate the macromolecular machinery for life.

In genetics, gene expression is the most fundamental level at which the genotype gives rise to the phenotype, i.e. observable trait. The genetic information stored in DNA represents the genotype, whereas the phenotype results from the "interpretation" of that information. Such phenotypes are often expressed by the synthesis of proteins that control the organism's structure and development, or that act as enzymes catalyzing specific metabolic pathways.

All steps in the gene expression process may be modulated (regulated), including the transcription, RNA splicing, translation, and post-translational modification of a protein. Regulation of gene expression gives control over the timing, location, and amount of a given gene product (protein or ncRNA) present in a cell and can have a profound effect on the cellular structure and function. Regulation of gene expression is the basis for cellular differentiation, development, morphogenesis and the versatility and adaptability of any organism. Gene regulation may also serve as a substrate for evolutionary change