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Proto-genes and de novo gene birth.

Carvunis AR, Rolland T, Wapinski I, Calderwood MA, Yildirim MA, Simonis N, Charloteaux B, Hidalgo CA, Barbette J, Santhanam B, Brar GA, Weissman JS, Regev A, Thierry-Mieg N, Cusick ME, Vidal M - Nature (2012)

Bottom Line: In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or 'non-genic' sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions.These translation events seem to provide adaptive potential, as suggested by their differential regulation upon stress and by signatures of retention by natural selection.Our work illustrates that evolution exploits seemingly dispensable sequences to generate adaptive functional innovation.

View Article: PubMed Central - PubMed

Affiliation: Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

ABSTRACT
Novel protein-coding genes can arise either through re-organization of pre-existing genes or de novo. Processes involving re-organization of pre-existing genes, notably after gene duplication, have been extensively described. In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or 'non-genic' sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions. Here we formalize an evolutionary model according to which functional genes evolve de novo through transitory proto-genes generated by widespread translational activity in non-genic sequences. Testing this model at the genome scale in Saccharomyces cerevisiae, we detect translation of hundreds of short species-specific open reading frames (ORFs) located in non-genic sequences. These translation events seem to provide adaptive potential, as suggested by their differential regulation upon stress and by signatures of retention by natural selection. In line with our model, we establish that S. cerevisiae ORFs can be placed within an evolutionary continuum ranging from non-genic sequences to genes. We identify ~1,900 candidate proto-genes among S. cerevisiae ORFs and find that de novo gene birth from such a reservoir may be more prevalent than sporadic gene duplication. Our work illustrates that evolution exploits seemingly dispensable sequences to generate adaptive functional innovation.

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Identification of proto-genes in a continuum ranging from non-genic ORFs to genesa, Characterization of candidate proto-genes (ORFs 0+ and ORFs1-4). Venn diagram not drawn to scale. b, The binary model of annotation (top) and the proposed continuum (bottom).
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Figure 4: Identification of proto-genes in a continuum ranging from non-genic ORFs to genesa, Characterization of candidate proto-genes (ORFs 0+ and ORFs1-4). Venn diagram not drawn to scale. b, The binary model of annotation (top) and the proposed continuum (bottom).

Mentions: Overall, our results show that de novo gene birth could proceed through proto-genes. From the initial comprehensive set of candidate proto-genes (all ORFs0 and ORFs1-4), we excluded ORFs0 that appear to lack translation signatures according to our stringent pipeline (Supplementary Fig. 6). The 25 ORFs4 that are longer than 300 nucleotides, show signatures of translation and are under purifying selection, can confidently be considered genes despite being weakly conserved. The remaining 1,891 ORFs (1,139 ORFs 0+ and 752 ORFs1-4) present characteristics intermediate between non-genic ORFs and genes, meeting our proto-gene designation (Fig. 4a, Supplementary Fig. 8 and Supplementary Table 3). We propose to place these ORFs in a continuum where strict annotation boundaries no longer have to be set (Fig. 4b).


Proto-genes and de novo gene birth.

Carvunis AR, Rolland T, Wapinski I, Calderwood MA, Yildirim MA, Simonis N, Charloteaux B, Hidalgo CA, Barbette J, Santhanam B, Brar GA, Weissman JS, Regev A, Thierry-Mieg N, Cusick ME, Vidal M - Nature (2012)

Identification of proto-genes in a continuum ranging from non-genic ORFs to genesa, Characterization of candidate proto-genes (ORFs 0+ and ORFs1-4). Venn diagram not drawn to scale. b, The binary model of annotation (top) and the proposed continuum (bottom).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3401362&req=5

Figure 4: Identification of proto-genes in a continuum ranging from non-genic ORFs to genesa, Characterization of candidate proto-genes (ORFs 0+ and ORFs1-4). Venn diagram not drawn to scale. b, The binary model of annotation (top) and the proposed continuum (bottom).
Mentions: Overall, our results show that de novo gene birth could proceed through proto-genes. From the initial comprehensive set of candidate proto-genes (all ORFs0 and ORFs1-4), we excluded ORFs0 that appear to lack translation signatures according to our stringent pipeline (Supplementary Fig. 6). The 25 ORFs4 that are longer than 300 nucleotides, show signatures of translation and are under purifying selection, can confidently be considered genes despite being weakly conserved. The remaining 1,891 ORFs (1,139 ORFs 0+ and 752 ORFs1-4) present characteristics intermediate between non-genic ORFs and genes, meeting our proto-gene designation (Fig. 4a, Supplementary Fig. 8 and Supplementary Table 3). We propose to place these ORFs in a continuum where strict annotation boundaries no longer have to be set (Fig. 4b).

Bottom Line: In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or 'non-genic' sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions.These translation events seem to provide adaptive potential, as suggested by their differential regulation upon stress and by signatures of retention by natural selection.Our work illustrates that evolution exploits seemingly dispensable sequences to generate adaptive functional innovation.

View Article: PubMed Central - PubMed

Affiliation: Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

ABSTRACT
Novel protein-coding genes can arise either through re-organization of pre-existing genes or de novo. Processes involving re-organization of pre-existing genes, notably after gene duplication, have been extensively described. In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or 'non-genic' sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions. Here we formalize an evolutionary model according to which functional genes evolve de novo through transitory proto-genes generated by widespread translational activity in non-genic sequences. Testing this model at the genome scale in Saccharomyces cerevisiae, we detect translation of hundreds of short species-specific open reading frames (ORFs) located in non-genic sequences. These translation events seem to provide adaptive potential, as suggested by their differential regulation upon stress and by signatures of retention by natural selection. In line with our model, we establish that S. cerevisiae ORFs can be placed within an evolutionary continuum ranging from non-genic sequences to genes. We identify ~1,900 candidate proto-genes among S. cerevisiae ORFs and find that de novo gene birth from such a reservoir may be more prevalent than sporadic gene duplication. Our work illustrates that evolution exploits seemingly dispensable sequences to generate adaptive functional innovation.

Show MeSH
Related in: MedlinePlus