P.S. I wrote this in Chinese blog, about 3 years ago? I was just learning the "new things" at that time. Now I translated them into English and as the first blog in my HP

Pseudogenes: Definition, Classification, and Terminology

What Are Pseudogenes?

Pseudogenes are generally considered to be defective copies of functional genes. They are characterized by:

Being non-coding sequences on the genome
Defective in structure or function
Highly similar in sequence to a functional "parent gene"
Mostly non-functional in terms of protein coding

Classification of Eukaryote Pseudogenes

Pseudogenes can be broadly categorized into four types:

Processed Pseudogenes
- Derived from retrotransposition of mature mRNAs
- Lack introns and often contain poly-A tails
Unprocessed Pseudogenes
- Arise from segmental duplications or low-copy repeats
- Retain the intron-exon structure of the parent gene
Unitary Pseudogenes (less common)
- Formed without gene duplication
- Result from loss-of-function mutations in a single-copy gene
Polymorphic Pseudogenes (rare)
- Appear non-functional in the reference genome
- May remain functional in non-reference genomes (e.g., in other populations or individuals)

Glossary of Related Terms

Expressed Sequence Tags (ESTs)
Short cDNA sequences used to identify transcriptionally active genes by mapping them to the genome.
Non-synonymous Substitutions
Base substitutions that alter the amino acid sequence of a protein.
Positive Selection
A form of natural selection that favors beneficial mutations. Alleles that enhance survival or reproduction tend to increase in frequency in the population.
Purifying Selection (Negative Selection)
A selective pressure that eliminates harmful mutations, leading to the removal of deleterious alleles from the gene pool.
Retrotransposition
The process by which an RNA intermediate is reverse transcribed and inserted back into the genome as DNA.
Synonymous Substitutions
Base substitutions that do not alter the amino acid sequence of a protein.

Terminological Challenges Surrounding Pseudogenes

As functional genomics advances, an increasing number of pseudogenes have been found to perform biological roles. This challenges the traditional notion of pseudogenes as merely non-functional relics.

As a result, many scholars argue that the term "pseudogene" may be misleading or even pejorative, potentially obscuring the true nature of these sequences. Alternative terms such as:

Defective gene copy
Retro-copy
Homologies

have been proposed to provide more neutral descriptions.

Furthermore, sequences identified through computational methods (e.g., sequence homology or annotation pipelines) are often better described as “pseudogene candidates” until their biological relevance is validated.

In modern genomics, the identification of pseudogenes has become a routine part of genome annotation, but the term should be applied with caution and ideally reserved for well-characterized cases.

reference

Cheetham, Seth W., Geoffrey J. Faulkner, and Marcel E. Dinger. "Overcoming challenges and dogmas to understand the functions of pseudogenes." Nature Reviews Genetics 21.3 (2020): 191-201.