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Genetic determinants of cell size at birth and their impact on cell cycle progression in Saccharomyces cerevisiae.

Truong SK, McCormick RF, Polymenis M - G3 (Bethesda) (2013)

Bottom Line: We found that although a large birth size strongly correlates with a large mean size, the converse relationship (i.e., small birth size vs. small mean size) is not as strong.In contrast, mutants that are born small are more likely to progress slower in the cell cycle.The majority of gene deletions that displayed such phenotypes affect protein synthesis or ribosome biogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843.

ABSTRACT
In most cases, cells must increase their size before they can divide. Hence, a small size has been used often as a phenotype for mutants that accelerate initiation of division, such as the celebrated WHI mutants of budding yeast. Recently, we measured the DNA content of all nonessential gene deletion strains in Saccharomyces cerevisiae. Surprisingly, there was little, if any, correlation between mean cell size and cell-cycle progression. Here, we examine this issue further, providing the first systematic analysis of genetic determinants of the cell size at birth. We found that although a large birth size strongly correlates with a large mean size, the converse relationship (i.e., small birth size vs. small mean size) is not as strong. Our data also suggest that mutants that are born large do not have a significant advantage for faster cell-cycle progression. In contrast, mutants that are born small are more likely to progress slower in the cell cycle. The majority of gene deletions that displayed such phenotypes affect protein synthesis or ribosome biogenesis. Overall, our data suggest that birth size may be a more informative parameter for cell-cycle progression than the mean size of a proliferating cell population. In contrast to WHI phenotype expectations, a small size is more likely to be associated with delayed cell-cycle progression.

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Cell size category determination. (A) Categories determined by deviations from wild-type mean xb (birth size). After calculating the mean and SD of xb for wild-type strains, mutants binned with xb less than two SDs below the wild-type mean xb were categorized as small (yellow); mutants binned with xb within two SDs of the wild-type mean xb were categorized as normal (light gray); and mutants binned with xb greater than two SDs above the wild-type mean xb were categorized as large (blue). The final category, overall, was comprised of all mutants. A normal distribution approximating wild-type xb was scaled and superimposed over the distribution of mutant xb values. (B) Categories determined as a proportion of all xb. Mutants in bins containing the smallest 5% xb were categorized as small (green); mutants in bins containing the largest 5% xb were categorized as large (purple); and mutants in bins that were not in small or large bins were categorized as normal (dark gray). The final category, overall, was comprised of all mutants.
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fig2: Cell size category determination. (A) Categories determined by deviations from wild-type mean xb (birth size). After calculating the mean and SD of xb for wild-type strains, mutants binned with xb less than two SDs below the wild-type mean xb were categorized as small (yellow); mutants binned with xb within two SDs of the wild-type mean xb were categorized as normal (light gray); and mutants binned with xb greater than two SDs above the wild-type mean xb were categorized as large (blue). The final category, overall, was comprised of all mutants. A normal distribution approximating wild-type xb was scaled and superimposed over the distribution of mutant xb values. (B) Categories determined as a proportion of all xb. Mutants in bins containing the smallest 5% xb were categorized as small (green); mutants in bins containing the largest 5% xb were categorized as large (purple); and mutants in bins that were not in small or large bins were categorized as normal (dark gray). The final category, overall, was comprised of all mutants.

Mentions: Illustration of cell size distribution parameters. For this analysis, five parameters, x0, xb, xd, xm, and xy, were determined for cell size distributions obtained from Jorgensen et al. (2002). The size distribution shown is from a wild-type sample shown in Jorgensen et al. (2002). For a given cell size distribution, x0 represents the start of the distribution and was determined visually from the distribution by excluding experimental noise. xd represents maximum daughter cell size and is a visual approximation of the mode of the cell size distribution. xb represents the maximum birth size and is approximated by the maximum of a proportion of the daughter cell interval. xm represents the mean cell size of the distribution. xy represents the end of the distribution and was determined as the last cell size in the distribution. Once parameters were determined, we calculated Spearman’s rank correlation coefficients between: xb and xm, xb and %G1, and xb and fitness for four categories of mutants (see Figure 2 for illustration of category determination). %G1 and fitness data were obtained from Hoose et al. (2012).


Genetic determinants of cell size at birth and their impact on cell cycle progression in Saccharomyces cerevisiae.

Truong SK, McCormick RF, Polymenis M - G3 (Bethesda) (2013)

Cell size category determination. (A) Categories determined by deviations from wild-type mean xb (birth size). After calculating the mean and SD of xb for wild-type strains, mutants binned with xb less than two SDs below the wild-type mean xb were categorized as small (yellow); mutants binned with xb within two SDs of the wild-type mean xb were categorized as normal (light gray); and mutants binned with xb greater than two SDs above the wild-type mean xb were categorized as large (blue). The final category, overall, was comprised of all mutants. A normal distribution approximating wild-type xb was scaled and superimposed over the distribution of mutant xb values. (B) Categories determined as a proportion of all xb. Mutants in bins containing the smallest 5% xb were categorized as small (green); mutants in bins containing the largest 5% xb were categorized as large (purple); and mutants in bins that were not in small or large bins were categorized as normal (dark gray). The final category, overall, was comprised of all mutants.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3755912&req=5

fig2: Cell size category determination. (A) Categories determined by deviations from wild-type mean xb (birth size). After calculating the mean and SD of xb for wild-type strains, mutants binned with xb less than two SDs below the wild-type mean xb were categorized as small (yellow); mutants binned with xb within two SDs of the wild-type mean xb were categorized as normal (light gray); and mutants binned with xb greater than two SDs above the wild-type mean xb were categorized as large (blue). The final category, overall, was comprised of all mutants. A normal distribution approximating wild-type xb was scaled and superimposed over the distribution of mutant xb values. (B) Categories determined as a proportion of all xb. Mutants in bins containing the smallest 5% xb were categorized as small (green); mutants in bins containing the largest 5% xb were categorized as large (purple); and mutants in bins that were not in small or large bins were categorized as normal (dark gray). The final category, overall, was comprised of all mutants.
Mentions: Illustration of cell size distribution parameters. For this analysis, five parameters, x0, xb, xd, xm, and xy, were determined for cell size distributions obtained from Jorgensen et al. (2002). The size distribution shown is from a wild-type sample shown in Jorgensen et al. (2002). For a given cell size distribution, x0 represents the start of the distribution and was determined visually from the distribution by excluding experimental noise. xd represents maximum daughter cell size and is a visual approximation of the mode of the cell size distribution. xb represents the maximum birth size and is approximated by the maximum of a proportion of the daughter cell interval. xm represents the mean cell size of the distribution. xy represents the end of the distribution and was determined as the last cell size in the distribution. Once parameters were determined, we calculated Spearman’s rank correlation coefficients between: xb and xm, xb and %G1, and xb and fitness for four categories of mutants (see Figure 2 for illustration of category determination). %G1 and fitness data were obtained from Hoose et al. (2012).

Bottom Line: We found that although a large birth size strongly correlates with a large mean size, the converse relationship (i.e., small birth size vs. small mean size) is not as strong.In contrast, mutants that are born small are more likely to progress slower in the cell cycle.The majority of gene deletions that displayed such phenotypes affect protein synthesis or ribosome biogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843.

ABSTRACT
In most cases, cells must increase their size before they can divide. Hence, a small size has been used often as a phenotype for mutants that accelerate initiation of division, such as the celebrated WHI mutants of budding yeast. Recently, we measured the DNA content of all nonessential gene deletion strains in Saccharomyces cerevisiae. Surprisingly, there was little, if any, correlation between mean cell size and cell-cycle progression. Here, we examine this issue further, providing the first systematic analysis of genetic determinants of the cell size at birth. We found that although a large birth size strongly correlates with a large mean size, the converse relationship (i.e., small birth size vs. small mean size) is not as strong. Our data also suggest that mutants that are born large do not have a significant advantage for faster cell-cycle progression. In contrast, mutants that are born small are more likely to progress slower in the cell cycle. The majority of gene deletions that displayed such phenotypes affect protein synthesis or ribosome biogenesis. Overall, our data suggest that birth size may be a more informative parameter for cell-cycle progression than the mean size of a proliferating cell population. In contrast to WHI phenotype expectations, a small size is more likely to be associated with delayed cell-cycle progression.

Show MeSH
Related in: MedlinePlus