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Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates.

Zhang ZD, Frankish A, Hunt T, Harrow J, Gerstein M - Genome Biol. (2010)

Bottom Line: Furthermore, we identify 11 unitary pseudogenes that are polymorphic - that is, they have both nonfunctional and functional alleles currently segregating in the human population.Comparing them with their orthologs in other primates, we find that two of them are in fact pseudogenes in non-human primates, suggesting that they represent cases of a gene being resurrected in the human lineage.This analysis of unitary pseudogenes provides insights into the evolutionary constraints faced by different organisms and the timescales of functional gene loss in humans.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. zdzmg@gersteinlab.org

ABSTRACT

Background: Unitary pseudogenes are a class of unprocessed pseudogenes without functioning counterparts in the genome. They constitute only a small fraction of annotated pseudogenes in the human genome. However, as they represent distinct functional losses over time, they shed light on the unique features of humans in primate evolution.

Results: We have developed a pipeline to detect human unitary pseudogenes through analyzing the global inventory of orthologs between the human genome and its mammalian relatives. We focus on gene losses along the human lineage after the divergence from rodents about 75 million years ago. In total, we identify 76 unitary pseudogenes, including previously annotated ones, and many novel ones. By comparing each of these to its functioning ortholog in other mammals, we can approximately date the creation of each unitary pseudogene (that is, the gene 'death date') and show that for our group of 76, the functional genes appear to be disabled at a fairly uniform rate throughout primate evolution - not all at once, correlated, for instance, with the 'Alu burst'. Furthermore, we identify 11 unitary pseudogenes that are polymorphic - that is, they have both nonfunctional and functional alleles currently segregating in the human population. Comparing them with their orthologs in other primates, we find that two of them are in fact pseudogenes in non-human primates, suggesting that they represent cases of a gene being resurrected in the human lineage.

Conclusions: This analysis of unitary pseudogenes provides insights into the evolutionary constraints faced by different organisms and the timescales of functional gene loss in humans.

Show MeSH
Dating the pseudogenization events. (a) Timing of the disruptive mutations that gave rise to human unitary pseudogenes by analyzing shared mutations. Only pseudogenes with annotations from orthologous mouse genes are shown. Ones without close paralogs are underlined. (b) Timing of several pseudogenization events that occurred in the human lineage after the human-chimp divergence. See Table S3 in Additional file 1 for the estimates and their standard errors. LCA, last common ancestor.
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Figure 5: Dating the pseudogenization events. (a) Timing of the disruptive mutations that gave rise to human unitary pseudogenes by analyzing shared mutations. Only pseudogenes with annotations from orthologous mouse genes are shown. Ones without close paralogs are underlined. (b) Timing of several pseudogenization events that occurred in the human lineage after the human-chimp divergence. See Table S3 in Additional file 1 for the estimates and their standard errors. LCA, last common ancestor.

Mentions: To estimate the time when functional genes were disabled to give rise to the human unitary pseudogenes, we identify the earliest shared ORF-disrupting mutations between humans and other mammals on the mammalian species tree. Very few pseudogenic mutations are shared outside of the primate clade. The most recent lineages where the occurrence of the pseudogenic mutations in the 47 annotated human unitary pseudogenes can generate their observed sharing pattern are illustrated on a primate phylogeny (Figure 5a). Such shared mutations indicate the pseudogenization events happened at every stage during primate evolution: from the human lineage alone to the last common ancestor of the great apes, the Old World monkeys, the New World monkeys, and the tarsiers.


Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates.

Zhang ZD, Frankish A, Hunt T, Harrow J, Gerstein M - Genome Biol. (2010)

Dating the pseudogenization events. (a) Timing of the disruptive mutations that gave rise to human unitary pseudogenes by analyzing shared mutations. Only pseudogenes with annotations from orthologous mouse genes are shown. Ones without close paralogs are underlined. (b) Timing of several pseudogenization events that occurred in the human lineage after the human-chimp divergence. See Table S3 in Additional file 1 for the estimates and their standard errors. LCA, last common ancestor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2864566&req=5

Figure 5: Dating the pseudogenization events. (a) Timing of the disruptive mutations that gave rise to human unitary pseudogenes by analyzing shared mutations. Only pseudogenes with annotations from orthologous mouse genes are shown. Ones without close paralogs are underlined. (b) Timing of several pseudogenization events that occurred in the human lineage after the human-chimp divergence. See Table S3 in Additional file 1 for the estimates and their standard errors. LCA, last common ancestor.
Mentions: To estimate the time when functional genes were disabled to give rise to the human unitary pseudogenes, we identify the earliest shared ORF-disrupting mutations between humans and other mammals on the mammalian species tree. Very few pseudogenic mutations are shared outside of the primate clade. The most recent lineages where the occurrence of the pseudogenic mutations in the 47 annotated human unitary pseudogenes can generate their observed sharing pattern are illustrated on a primate phylogeny (Figure 5a). Such shared mutations indicate the pseudogenization events happened at every stage during primate evolution: from the human lineage alone to the last common ancestor of the great apes, the Old World monkeys, the New World monkeys, and the tarsiers.

Bottom Line: Furthermore, we identify 11 unitary pseudogenes that are polymorphic - that is, they have both nonfunctional and functional alleles currently segregating in the human population.Comparing them with their orthologs in other primates, we find that two of them are in fact pseudogenes in non-human primates, suggesting that they represent cases of a gene being resurrected in the human lineage.This analysis of unitary pseudogenes provides insights into the evolutionary constraints faced by different organisms and the timescales of functional gene loss in humans.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. zdzmg@gersteinlab.org

ABSTRACT

Background: Unitary pseudogenes are a class of unprocessed pseudogenes without functioning counterparts in the genome. They constitute only a small fraction of annotated pseudogenes in the human genome. However, as they represent distinct functional losses over time, they shed light on the unique features of humans in primate evolution.

Results: We have developed a pipeline to detect human unitary pseudogenes through analyzing the global inventory of orthologs between the human genome and its mammalian relatives. We focus on gene losses along the human lineage after the divergence from rodents about 75 million years ago. In total, we identify 76 unitary pseudogenes, including previously annotated ones, and many novel ones. By comparing each of these to its functioning ortholog in other mammals, we can approximately date the creation of each unitary pseudogene (that is, the gene 'death date') and show that for our group of 76, the functional genes appear to be disabled at a fairly uniform rate throughout primate evolution - not all at once, correlated, for instance, with the 'Alu burst'. Furthermore, we identify 11 unitary pseudogenes that are polymorphic - that is, they have both nonfunctional and functional alleles currently segregating in the human population. Comparing them with their orthologs in other primates, we find that two of them are in fact pseudogenes in non-human primates, suggesting that they represent cases of a gene being resurrected in the human lineage.

Conclusions: This analysis of unitary pseudogenes provides insights into the evolutionary constraints faced by different organisms and the timescales of functional gene loss in humans.

Show MeSH