One might think that identical-twin bacteria—clones of each other—would grow up and live very similarly. But a study published today in Science that examined individual bacterial cells in detail found that genetically identical E. Coli cells actually seem to express their genes quite differently, simply because of the random accidents of how their molecular machinery happens to operate.
“The paper is quite rich,” said Sanjay Tyagi, a molecular biologist at New Jersey Medical School who was not involved in the research [but published a perspectives piece on it]. “People think that if an organism has a particular genotype, it determines its phenotype [observable characteristics]–that there’s a one-to-one relationship,” said Tyagi. “But as it turns out, [differences in gene expression] can arise just from chance.” [The Scientist]
Specifically, a team at Harvard University sorted through E. Coli bacteria, analyzing them one at a time. They looked at the amount of mRNA (messenger molecules that carry protein blueprints) and the amount of protein built from those blueprints. They noticed a lot of variation–or “noise”–from one cell to the next.
At any given moment, a fraction of cells didn’t have a single molecule of mRNA or protein from a given gene, and a surprising subset of genes–more than 20 percent of those analyzed–expressed one or fewer copies of protein per cell. The ability to measure with this kind of single-molecule sensitivity is valuable for single-cell studies, said [senior researcher on the study, Sunney] Xie. [The Scientist]
Besides each genome varying in how it expressed itself, the researchers also found a discrepancy with, what Science News reports as a “central dogma” of molecular biology: the amount of mRNA for a specific protein and the amount of that protein should correspond. The researchers counted mRNA molecules and proteins associated with 1,018 genes in each microbe. More mRNA did not necessarily mean more of the associated protein: Instead, they discovered that each cell varied in the exact number of proteins present and the amount of mRNA it employed. As The Scientist reports, Tyagi suspects that short life of mRNA (only minutes) and of E. Coli (which divides about every 30 minutes) could, in part, cause these random variations. The mRNA might disappear during counting while the longer-lived protein made from it remains, and that dividing E. Coli might throw off the count by passing proteins from parent to offspring.
The researchers think the study may help research practice and perhaps to understand one cause of antibiotic resistance.
The results provide a “cautionary note” to researchers when they measure mRNA levels in single cells, Xie says: They need to take into account that the mRNA level in a cell does not reflect the level of its associated protein. Xie and his team next will study how this “noise” might contribute to antibiotic resistance in bacteria. [Science News]
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