Human Lineage‐Specific Gene Inactivation


Pseudogenes are nonfunctional vestiges of genes. Investigating genes that were inactivated specifically on the human lineage or within humans can reveal the genetic basis of interspecies differences between humans and chimpanzees and interindividual differences within humans. It can also help understand the selective pressures that altered during human evolution or vary among human populations. Recent genome‐wide surveys showed that human‐specific pseudogenisation events occurred much more frequently to chemosensory and immune response genes than to other genes. Although nondeleterious pseudogenisation events were traditionally considered to be neutral, emerging evidence suggests that some of them are beneficial. One well‐characterised case is the human CASP12 locus, where the null allele decreases the incidence of sepsis and has apparently been selected for in human evolution. Exploration of roles of pseudogenisation in genome evolution and phenotype evolution has started.

Key Concepts:

  • Pseudogenes in our genome can be (1) shared with other species, (2) functional only in non‐human species or (3) functional in some but not all humans.

  • According to the ‘less‐is‐more’ hypothesis, human‐specific pseudogenes that are functional in related primates reveal insight into how gene loss helped shape human evolution.

  • Large‐scale human genetic variation databases reveal hundreds of segregating pseudogenes, suggesting individual and population differences in functional gene content.

  • Although most gene‐disrupting variants are under negative selective pressure, some population genetic studies of segregating pseudogene loci reveal signatures of positive selection for the disrupted allele, suggesting that gene loss can be beneficial.

  • Among fixed and segregating human‐specific pseudogenes, chemoreception and immune response are over‐represented functional categories.

Keywords: human; evolution; chimpanzee; pseudogene; positive selection

Figure 1.

(a) Geographical distribution of pseudogene (orange) and intact (blue) MAGEE2 alleles in different populations. Pie areas are proportional to sample sizes. (b) Median‐joining network of inferred MAGEE2 haplotypes reveal lower diversity levels in haplotypes containing the nonsense SNP rs1343879 (arrow). Circle areas are proportional to the haplotype frequency and are color coded according to population: CEU in yellow, CHB in green, LWK in pink, and YRI in red. Lines represent mutational steps between them (one or two steps, according to length). Used with permission from Yngvadottir et al. . © Elsevier.

Figure 2.

Nucleotide diversity in the CASP12 gene in noncoding regions of the pseudogenised allele and functional allele. The exon structure for CASP12 is shown in thick blue bars. Nucleotide diversity (π) is significantly lower near the disrupting mutation (*) in exon 4 of the CASP12 pseudogenized allele (red) than is observed in the functional allele (green). Red circles and green dots show the percent nucleotide diversity in the pseudogenized and functional alleles, respectively, at each of nine noncoding regions within and around the gene (black bars). The rectangles surrounding the dots and squares show ±1 standard error. The green dotted line is the average nucleotide diversity for the functional allele. The decreased diversity in the pseudogenised allele near the disrupting mutation is indicative of a selective sweep for this pseudogenized allele. Adapted from Wang et al. .

Figure 3.

The relative size of chewing muscles differs greatly between humans and their primate relatives as a result of pseudogenization of human MYH16. The differences in musculature are reflected in the morphology of such craniofacial features as the temporal fossa and zygomatic arch (highlighted in red) in skulls from macaque (a–c), gorilla (d–f) and human (g–i). Adapted by permission from Macmillan Publishers Ltd., Stedman et al., Copyright (2004).



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Web Links

Comprehensive Pseudogene Database accessed on 14 June 2013.

1000 Genomes Project accessed on 14 June 2013.

NHLBI Exome Sequencing Project accessed on 14 June 2013.

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How to Cite close
Grus, Wendy E, and Zhang, Jianzhi(Sep 2013) Human Lineage‐Specific Gene Inactivation. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020835.pub2]