Pseudogenes at Work

Pseudogenes are DNA sequences that look a lot like genes but appear defective in some way. Some pseudogenes, called processed pseudogenes, are missing pieces called introns, which functional genes normally have. Another group of pseudogenes, called unprocessed pseudogenes, retains the introns, but has stop signals in the wrong places. The pseudogenes in both of these groups are similar to other, functional gene sequences. Another type, unitary pseudogenes, are not duplicated copies of functional genes, but look like genes that have been disrupted by mutations. The status of pseudogenes and evidence that many of them are functional is the subject of a recent review paper.[1]

Pseudogenes have been found in every animal species investigated. Nearly 15,000 pseudogenes have been identified in humans, which is within the range of 10,000 to 20,000 typical for other species. Since pseudogenes are assumed to be non-functional, they are usually not included in genomic analyses. However, pseudogenes that have a function should be included in studies of genomic studies. Thus it is important to develop good methodologies for determining whether an assumed pseudogene has a function.

Several types of functions have been identified for various pseudogenes. A pseudogene may have tissue-specific activity. For example, PGK2 is active in human testis. Immunoglobulin pseudogenes are involved in immune response in chickens. Some are involved in disease. Examples include PRSS3P2, which causes hereditary pancreatitis, and POUSF1B which promotes tumor growth in humans. Cellular growth is affected by putative pseudogenes NANOGP8 and ΨCX43.  Several pseudogenes affect gene regulation, including human SRGAP2C, HMGA1-p and PTENP1, and NOS in Lymnaea snails. The beta globin pseudogene, HBBP1, is of particular interest.[2]

Diagram of beta globin gene cluster, showing the location of the pseudogene, Ψβ, between the embryonic genes (green) and the adult genes (blue). See text below. Image: GRI

Human hemoglobin is composed of four subunits: two alpha globins and two beta globins. The alpha globin genes are located on chromosome 16, and the beta globins on chromosome 11. There is a series of three beta globin genes expressed in the embryo and two genes expressed in the adult. A pseudogene is located between these two sets. It is similar to the regular beta globin genes, but has stop codons that prevent it from producing normal beta globin. The same set of genes is present in chimpanzees. Assuming that the pseudogene is due to an error in DNA copying, the presence of the same error in humans and chimpanzees has been used to argue that this can only be explained by common ancestry of the two species. This argument was advanced for many years, but evidence that the pseudogene is functional removes the force of this argument.

The location of the beta globin pseudogene between the embryonic genes and the adult genes was suggestive of a role in gene regulation, and this has been confirmed more recently.[3] Preventing transcription of the pseudogene (making an RNA copy) does not affect the switch from embryonic to adult globins, but deleting the pseudogene causes continued expression of embryonic beta globin. It seems that the pseudogene interacts with neighboring portions of the chromosome so that it covers up the adult genes during embryonic development and prevents them from being active. About the time of birth, the chromosome changes shape and the pseudogene changes its point of contact so that it covers up the embryonic genes and exposes the adult genes to be activated. Thus the pseudogene acts as a genetic switch to regulate the timing of gene expression.

The history of pseudogenes in general, and of the beta globin pseudogene in particular, serve as a caution against accepting scientific consensus as a basis for denying the biblical creation story.

James Gibson, PhD
Geoscience Research Institute


[1] Cheetham SW, Faulkner GJ, Dinger ME, 2019.  Overcoming challenges and dogmas to understand the functions of pseudogenes.  Nat Rev Genet doi:10.1038/s41576-019-0196-1

[2] See

[3] Huang P, CA Keller, B Giardine, JD Grevet, JOJ Davies, JR Hughes, R Kurita, Y Nakamura, RC Hardison and GA Blobel. 2017. Comparative analysis of three-dimensional chromosomal architecture identifies a novel fetal hemoglobin regulatory element. Genes and Development 31:1704-1713. Doi: