Any organism is a by-product of both its genetic makeup and the environment. To understand this in detail, we must first appreciate some basic genetic vocabulary and concepts. Here, we provide definitions for the terms genotype and phenotype, discuss their relationship and take a look at why and how we might choose to study them.
What is the definition of a genotype?
In biology, a gene is a section of DNA that encodes a trait. The precise arrangement of nucleotides (each composed of a phosphate group, sugar and a base) in a gene can differ between copies of the same gene. Therefore, a gene can exist in different forms across organisms. These different forms are known as alleles. The exact fixed position on the chromosome that contains a particular gene is known as a locus.
A diploid organism either inherits two copies of the same allele or one copy of two different alleles from their parents. If an individual inherits two identical alleles, their genotype is said to be homozygous at that locus.
However, if they possess two different alleles, their genotype is classed as heterozygous for that locus. Alleles of the same gene are either autosomal dominant or recessive. An autosomal dominant allele will always be preferentially expressed over a recessive allele.
The subsequent combination of alleles that an individual possesses for a specific gene is their genotype.
Let’s look at a classic example – eye color.
- A gene encodes eye color.
- In this example, the allele is either brown, or blue, with one inherited from the mother, and the other inherited from the father.
- The brown allele is dominant (B), and the blue allele is recessive (b). If the child inherits two different alleles (heterozygous) then they will have brown eyes. For the child to have blue eyes, they must be homozygous for the blue eye allele.
Figure 1: Inheritance chart detailing how an individual may inherit blue or brown eyes depending on the alleles carried by their parents, with the brown eye color allele being dominant and the blue eye color allele being recessive.
Other examples of genotype include:
- Hair color
- Shoe size
What is the definition of a phenotype?
The sum of an organism’s observable characteristics is their phenotype. A key difference between phenotype and genotype is that, whilst genotype is inherited from an organism’s parents, the phenotype is not.
Whilst a phenotype is influenced the genotype, genotype does not equal phenotype. The phenotype is influenced by the genotype and factors including:
- Epigenetic modifications
- Environmental and lifestyle factors
Figure 2: Flamingos are naturally white in color, it is only the pigments in the organisms that they eat that cause them to turn vibrantly pink.
Environmental factors that may influence the phenotype include nutrition, temperature, humidity and stress. Flamingos are a classic example of how the environment influences the phenotype. Whilst renowned for being vibrantly pink, their natural color is white – the pink color is caused by pigments in the organisms in their diet.
A second example is an individual’s skin color. Our genes control the amount and type of melanin that we produce, however, exposure to UV light in sunny climates causes the darkening of existing melanin and encourages increased melanogenesis and thus darker skin.
Genotype vs phenotype: observing
Observing the phenotype is simple – we take a look at an organism’s outward features and characteristics, and form conclusions about them. Observing the genotype, however, is a little more complex.
Genotyping is the process by which differences in the genotype of an individual are analyzed using biological assays. The data obtained can then be compared against either a second individual’s sequence, or a database of sequences.
Figure 3: A workflow depicting the various steps of whole genome sequencing (WGS).
(WGS) allows entire sequences to be obtained. An efficient process that is increasingly affordable, WGS involves using high-throughput sequencing techniques such as single-molecule real-time (SMRT) sequencing to identify the raw sequence of nucleotides constituting an organism’s DNA.
WGS is not the only way to analyze an organism’s genome – a variety of methods are available.
Why is it important to study genotype vs phenotype?
Understanding the relationship between a genotype and phenotype can be extremely useful in a variety of research areas.
A particularly interesting area is pharmacogenomics. Genetic variations can occur in liver enzymes required for drug metabolism, such as CYP450. Therefore, an individual’s phenotype, i.e. their ability to metabolize a specific drug, may vary depending on which form of the enzyme-encoding gene they possess. For pharmaceutical companies and physicians, this knowledge is key for determining recommended drug dosages across populations.
Making use of genotyping and phenotyping techniques in tandem appear to be better than using genotype tests alone. In a comparative clinical pharmacogenomics study, a multiplexing approach identified greater differences in drug metabolism capacity than was predicted by genotyping alone. This has important implications for personalized medicine and highlights the need to be cautious when exclusively relying on genotyping.
How can we study the relationship between genotype and phenotype?
Using animal models such as mice, scientists can genetically modify an organism so that it no longer expresses a specific gene – known as knockout mice. By comparing the phenotype of this animal to the wild type phenotype (i.e. the phenotype that exists when the gene has not been removed), we can study the role of certain genes in delivering certain phenotypes.
The Mouse Genome Informatics (MGI) initiative has compiled a database of thousands of phenotypes that can be created and studied, and the genes that must be knocked out to produce each specific phenotype.