Gene expression refers to the process by which the genetic code, or DNA, is used to synthesize functional gene products such as proteins and RNA. The entirety of an organism’s observable traits, also called its phenotype, is dependent on which genes are expressed in each cell at a given time. While every cell contains the organism’s full genome, each cell type only expresses a subset of genes that are required for its specific structure and function. Gene expression is regulated by intricate cellular mechanisms that control whether transcription and translation of a gene will occur.
Introduction
An organism’s observable characteristics, or its phenotype, include morphological features like height and eye color as well as physiological traits like blood type. The sum total of an organism’s phenotypes comprise its overall observable traits. These traits are determined by the organism’s genetic makeup, or genotype, along with environmental influences. The link between genotype and phenotype is created by gene expression – the transcription of genetic information encoded in DNA into functional products like RNA and protein. Gene expression controls when and where each gene is turned “on” or “off” in the body’s myriad cell types. While every cell contains the full complement of an organism’s DNA, specialized cells like neurons or hepatocytes express only a subset of genes that are required for that particular cell’s structure and function.
Central Dogma of Molecular Biology
The central dogma of molecular biology describes the flow of genetic information within the cell from DNA to RNA to protein. It states that DNA encodes the necessary information for synthesizing all of an organism’s proteins. This genetic code must be first transcribed into messenger RNA (mRNA) – a molecular intermediate. The mRNA then provides the template for protein synthesis via translation. Gene expression therefore requires both transcription and translation of the appropriate genes. The entirety of an organism’s observable physical and biochemical traits – the phenotype – is determined by which genes are expressed as functional proteins in each cell.
Transcriptional Regulation
Transcription is the process by which the genetic code in DNA is copied into transient mRNA molecules. This occurs in the nucleus where the DNA resides. Transcription is the first step in gene expression and is tightly regulated by proteins called transcription factors. Transcription factors bind to specific DNA sequences called enhancers or promoters located near the gene of interest. Depending on the transcription factor, it can either activate or repress transcription. Activating transcription factors recruit RNA polymerase and general transcription factors which then facilitate transcription of the downstream gene. Repressors conversely block the transcription machinery from accessing the DNA.
Post-transcriptional Regulation
Following transcription, further regulation of gene expression can occur through post-transcriptional mechanisms that control the mRNA’s stability, localization, and translation. The polyadenylation of mRNA transcripts for instance increases their stability, while binding of regulatory miRNAs leads to targeted mRNA degradation. Transport of mRNA out of the nucleus to the cytoplasm also regulates gene expression spatially. Once in the cytoplasm, the translation of mRNA into protein can be regulated via RNA binding proteins that block the ribosomal translation machinery. Overall, multiple mechanisms exist post-transcriptionally to fine tune when and where gene expression occurs.
Translational Regulation
Translation is the process by which the mRNA code is decoded into a polypeptide chain via tRNA molecules in the ribosome. Like transcription, translation is also tightly regulated in the cell to control gene expression. Translational regulation predominantly occurs at the initiation phase and involves regulatory proteins called translation factors. Initiation factors regulate assembly of the ribosomal complex onto the mRNA transcript. Release factors induce hydrolysis of the completed polypeptide from the tRNA chain once translation is terminated. Control of translation initiation therefore determines if and when protein synthesis will occur. Other mechanisms like phosphorylation can also regulate the activity of components of the translation machinery.
Epigenetic Regulation
In addition to genetic regulation, gene expression is also controlled by epigenetic mechanisms that alter the structure and accessibility of DNA without changing its sequence. This includes DNA methylation and histone modification. DNA methylation involves addition of methyl groups to CpG dinucleotides which typically silences gene expression. Histone proteins that DNA wraps around can also be chemically modified via acetylation, methylation, etc. These modifications influence how tightly or loosely packed the DNA is and thus accessibility for transcription. Epigenetics allow for phenotypic variation without mutation and control patterns of gene expression during development.
Differential Gene Expression
While every somatic cell contains the organism’s full genome, only a subset of genes is expressed in any given cell. Those genes required for that particular cell’s functions are expressed, while unnecessary genes remain silent. For example, the insulin gene is only expressed in pancreatic beta cells. This differential gene expression controlled by regulatory mechanisms allows cells to have specialized structures and perform specific tasks. Cell-specific transcriptional regulators like lineage determining transcription factors activate expression of only those genes needed in that cell type.
Observable Traits and Phenotypes
An organism’s observable traits and overall phenotype are determined by which genes are expressed in each cell type. For instance, genes encoding melanin production and deposition are expressed in melanocytes to give skin and hair their pigmentation. Genes controlling limb development are expressed by cells in the limb buds to direct proper arm and leg formation. Disruptions in these regulatory processes can lead to altered phenotypes like albinism or limb deformities. Variation in observable traits even between individuals of a species is largely due to differences in gene expression patterns rather than gene sequence variation.
Morphological Traits
Morphological phenotypes like height, eye color, and hair texture are dictated by gene expression. For example, the PAX3 transcription factor is expressed in melanoblasts and turns on expression of genes involved in melanin synthesis like TYR, TYRP1, and DCT. The precise level of pigments like eumelanin and pheomelanin produced determines hair and eye color. Similarly, height is largely determined by expression of the growth hormone gene in the anterior pituitary gland, which regulates production of insulin-like growth factors that stimulate skeletal growth.
Physiological Traits
Physiological phenotypes like blood type and drug metabolism patterns also correspond to gene expression. Expression of ABO glycosyltransferases which add sugars to the H antigen on red blood cells determines whether an individual has type A, B, AB or O blood. For drug metabolism, expression levels of cytochrome P450 (CYP) enzymes in the liver control the rate of drug catabolism. Over 1,000 CYP genes exist, and expression levels vary substantially between individuals, affecting drug response.
Behavioral Traits
Behavioral phenotypes can also correlate with gene expression patterns. For instance, the vasopressin 1a receptor gene is expressed at higher levels in the ventral pallidum of monogamous vole species compared to promiscuous ones. This receptivity to vasopressin signaling mediates monogamous behavior. In humans as well, increased monoamine oxidase A expression, which degrades neurotransmitters like serotonin and dopamine, has been associated with aggressive behavior.
Single Gene Effects
While most phenotypic traits result from small contributions of many genes, some characteristics are strongly determined by the expression pattern of a single gene. Often these result in mendelian or monogenic diseases when the gene is defective. For example, expression of the Huntington’s disease gene with an expanded trinucleotide repeat causes neurodegeneration and psychiatric problems. Similarly, a defective cystic fibrosis transmembrane receptor gene leads to thick mucus secretion in the airways and other organ systems.
Complex Traits
In contrast to single gene effects, most observable traits and disease susceptibilities depend on a combination of multiple genes along with environmental factors. These are considered complex traits since they do not follow strict mendelian inheritance patterns. Even heights varies substantially between individuals due to variation in thousands of genes that regulate growth as well as nutrition. Similarly, propensity for heart disease, diabetes, and cancer involves both genetic and lifestyle factors. Genome wide association studies help identify common genetic variants associated with these complex traits.
Genetic Interactions
In addition to additive effects, gene products can also interact with one another in ways that affect phenotype. For instance, some mutations alone have minimal effect but cause severe defects when combined in the same individual, a phenomenon called synthetic lethality. Epistasis is another example in which the phenotype produced by one gene depends on the genotype of a different gene. These genetic interactions demonstrate that phenotypic expression integrates inputs from many genes.
Environmental Effects
While an organism’s genotype remains fixed, gene expression patterns respond dynamically to changes in the environment. This allows phenotypes to be tuned to match environmental conditions. For example, exposure to UV radiation causes increased expression of melanin production genes, leading to tanning of the skin. Thermoregulation represents another example, as cooler temperatures induce adipocyte differentiation and fat production to insulate the body. The environment can profoundly impact phenotypes through regulation of gene expression.
Evolution of Gene Expression
Changes in gene expression likely contribute significantly to phenotypic evolution and divergence between species. Mutations in regulatory sequences that alter expression of a target gene facilitate rapid evolutionary changes. For instance, increased expression of the pituitary growth hormone gene boosted growth rates in domestic cattle compared to the wild aurochs. Additionally, gene duplications provide redundancy that permits previously lethal mutations, allowing neofunctionalization of duplicate copies. Altered gene regulation therefore provides a flexible mechanism for phenotypic adaptation.
Conclusion
In summary, an organism’s observable traits and overall phenotype are dependent on which genes are expressed in each of its cells and tissues. While every cell possesses the full genome, only a subset of genes is actively transcribed and translated into proteins in any given cell type. The regulation of gene expression controls this selective gene activity and thereby sculpts phenotypic outcomes. A diversity of regulatory mechanisms modulate transcription, mRNA processing, and translation to fine tune where, when, and to what degree each gene is expressed. These processes ultimately forge the link between genotype and phenotype that underlies all aspects of an organism’s observable traits.
