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Intragenic tandem repeats generate functional variability

Abstract

Tandemly repeated DNA sequences are highly dynamic components of genomes1. Most repeats are in intergenic regions, but some are in coding sequences or pseudogenes2. In humans, expansion of intragenic triplet repeats is associated with various diseases, including Huntington chorea and fragile X syndrome3,4. The persistence of intragenic repeats in genomes suggests that there is a compensating benefit. Here we show that in the genome of Saccharomyces cerevisiae, most genes containing intragenic repeats encode cell-wall proteins. The repeats trigger frequent recombination events in the gene or between the gene and a pseudogene, causing expansion and contraction in the gene size. This size variation creates quantitative alterations in phenotypes (e.g., adhesion, flocculation or biofilm formation). We propose that variation in intragenic repeat number provides the functional diversity of cell surface antigens that, in fungi and other pathogens, allows rapid adaptation to the environment and elusion of the host immune system.

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Figure 1: S. cerevisiae genes containing conserved intragenic repeats.
Figure 2: Intragenic repetitive domains vary in size.
Figure 3: Intragenic repeats are hot spots for recombination.
Figure 4: Repeats in pseudogenes provide an additional source of variability.
Figure 5: Instability of the FLO1 repeats generates functional variability.

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Acknowledgements

We thank A. Sinskey, A. Amon, T. Petes and all members of the laboratory of G.R.F. for discussions; K. Walker for assistance with the bioinformatics; and T. DiCesare for help with the graphics. K.J.V. is a post-doctoral fellow of the Fund for Scientific Research Flanders (F.W.O. Vlaanderen) and a D. Collen Fellow of the Belgian American Educational Foundation (B.A.E.F.). G.R.F. is an American Cancer Society Professor of Genetics. This research was supported by a grant from the US National Institutes of Health to G.R.F.

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Correspondence to Gerald R Fink.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Size comparison of the repetitive domains of the 29 S. cerevisiae ORFs containing long (≥ 40 nt) intragenic repeats in six different yeast strains. (PDF 1148 kb)

Supplementary Fig. 2

Size comparison of the repetitive domains of the 15 S. cerevisiae ORFs containing short (< 40 nt) intragenic repeats in six different yeast strains. (PDF 1069 kb)

Supplementary Fig. 3

Size comparison of 16 ORFs without intragenic repeats in six yeast strains. (PDF 1127 kb)

Supplementary Fig. 4

Alignment of the FLO1 repetitive region of the wild-type S. cerevisiae S288C strain and that of shorter FLO1 alleles. (PDF 1413 kb)

Supplementary Fig. 5

Model of recombination of intragenic repeats. (PDF 1087 kb)

Supplementary Table 1

ETANDEM analysis of all S. cerevisiae ORFs that contain intragenic repeats. (PDF 191 kb)

Supplementary Table 2

Yeast strains. (PDF 31 kb)

Supplementary Table 3

PCR primer sequences. (PDF 39 kb)

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Verstrepen, K., Jansen, A., Lewitter, F. et al. Intragenic tandem repeats generate functional variability. Nat Genet 37, 986–990 (2005). https://doi.org/10.1038/ng1618

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