What is the Difference Between Forward and Reverse Genetics

The main difference between forward and reverse genetics is that forward genetics is the study of a gene responsible for a particular phenotype whereas reverse genetics is the study of the change of a particular phenotype in response to the alteration of the corresponding gene. Furthermore, forward genetics helps in the identification or isolation of random mutations, which affect the phenotype of interest while reverse genetics has a role in the deletion of the gene or introduction of a mutation to a gene already sequenced. 

Forward and reverse genetics are two approaches in functional genomics which assess the gene function by using the information by structural genomics. 

Key Areas Covered 

1. What is Forward Genetics
     – Definition, Facts, Tools
2. What is Reverse Genetics
     – Definition, Facts, Tools
3. What are the Similarities Between Forward and Reverse Genetics
     – Outline of Common Features
4. What is the Difference Between Forward and Reverse Genetics
     – Comparison of Key Differences

Key Terms 

Forward Genetics, Functional Genomics, Gene Disruption, In Vitro Mutagenesis, Phenotype, Reverse Genetics

What is Forward Genetics 

Forward genetics is an approach to functional genomics. It is the traditional method that studies the function of a gene starting from a mutant phenotype. Hence, the main objective of forward genetics is to identify the corresponding gene sequence for a mutant phenotype. Here, mutant phenotypes can occur in two methods: spontaneous mutations and induced mutations. Spontaneous mutations are the natural changes that occur in the gene sequence due to errors in the replication. Moreover, mutagens are responsible for induced mutations.  

Figure 1: Blue Color is a Mutant Phenotype in Lobster

Furthermore, random mutations can be induced by mutagens in order to generate the desired phenotype. Then, the corresponding genetic makers are genetically mapped by using crossbreeding methods. Upon identification of the mutant allele corresponding to the mutant phenotype, its expression is analyzed by microarrays.  

What is Reverse Genetics 

Reverse genetics is the opposite approach to the forward genetics in functional genomics. Therefore, it involves the study of the gene function, starting from an already known gene sequence. Scientists alter the sequence of the gene in order to study the effect of a particular alteration on the corresponding phenotype.  

Figure 2: Deviating Phenotypes Induced in Gene-Disruption Library Transformants in Physcomitrella

Moreover, the two main tools of reverse genetics are in vitro mutagenesis and gene disruption. In vitro mutagenesis is responsible for introducing mutations in the desired gene sequence. Furthermore, the methods that can introduce mutations in a gene sequence are random mutagenesis, site-directed mutagenesis, homologous recombination, and transposable element excision. Besides, gene disruption is responsible for the inactivation of the gene or its product. Gene knockout is another name for this process. Here, a cloned gene can be integrated into the genome of the wild-type organism, mutating the gene. If not, the function of the gene can be silenced by RNA interference. Ultimately, the effect of the alteration is observable in the successive generations.  

Similarities Between Forward and Reverse Genetics 

• Forward and reverse genetics are two opposite approaches of functional genomics.  
• Both are involved in the study of the relationship between the gene sequence and the corresponding phenotype. In other words, both approaches study the function of a gene. 
• Also, both high-throughput or large-scale experimental methods and statistical analysis are in the experimental procedure of both types of approaches. 

Difference Between Forward and Reverse Genetics 

Definition 

Forward genetics refers to the approach of determining the genetic basis responsible for a phenotype while reverse genetics refers to the approach used to understand the function of a gene by analyzing the phenotypic effects of specific engineered gene sequences. Thus, this is the main difference between forward and reverse genetics.

Starts from 

A major difference between forward and reverse genetics is their start. Forward genetics starts from the phenotype while reverse genetics starts from the gene sequence. 

Type of Study 

Moreover, forward genetics helps in the identification of the gene responsible for a particular phenotype while reverse genetics is involved in the function or the possible phenotype of an altered gene. 

Tools 

The main tool of forward genetics is random mutations while in vitro mutagenesis and gene disruption are the two tools of reverse genetics. Hence, this is another difference between forward and reverse genetics.

Conclusion 

Forward genetics is an approach which studies the gene sequence of a particular phenotype while reverse genetics studies the effect of alterations of a gene sequence on the phenotype. Both forward and reverse genetics are two opposite methods of functional genomics. They study the relationship between the gene sequence and the phenotype. Thus, the main difference between forward and reverse genetics is the direction of the study.

References:

1. Griffiths AJF, Miller JH, Suzuki DT, et al. An Introduction to Genetic Analysis. 7th edition. New York: W. H. Freeman; 2000. Reverse genetics. Available Here

Image Courtesy:

1. “Blue-lobster” By Steven G. Johnson – Own work (CC BY-SA 3.0) via Commons Wikimedia  
2. “Physcomitrella knockout mutants” By Ralf Reski – Egener et al. BMC Plant Biology 2002 2:6 doi:10.1186/1471-2229-2-6 (CC BY 1.0) via Commons Wikimedia