Abstract
One of the basic postulates of molecular evolution is that functionally important genes should evolve slower than genes of lesser significance. Essential genes, whose knockout leads to a lethal phenotype are considered of high functional importance, yet whether they are truly more conserved than nonessential genes has been the topic of much debate, fuelled by a host of contradictory findings. Here we conduct the first large-scale study utilizing genome-scale metabolic modeling and spanning many bacterial species, which aims to answer this question. Using the novel Media Variation Analysis, we examine the range of conservation of essential vs. nonessential metabolic genes in a given species across all possible media. We are thus able to obtain for the first time, exact upper and lower bounds on the levels of differential conservation of essential genes for each of the species studied. The results show that bacteria do exhibit an overall tendency for differential conservation of their essential genes vs. their non-essential ones, yet this tendency is highly variable across species. We show that the model bacterium E. coli K12 may or may not exhibit differential conservation of essential genes depending on its growth medium, shedding light on previous experimental studies showing opposite trends.
Highlights
A gene can be classified as essential or nonessential, depending on its effect on an organism's fitness [1]
We show that the tendency to differentially conserve essential genes varies strikingly across bacterial species and growth media (Results 3.2 and 3.4), and that some bacteria used in previous experiments are not expected to follow the KOR-hypothesis—possibly explaining the contradictory experimental results obtained in the past (Results 3.2)
These results were obtained via the use of two new computational approaches—Media Variation Analysis (MVA) and Essential Gene Sets (EGS); both methods give a media-independent score for the differential conservation of an organism’s essential genes
Summary
A gene can be classified as essential or nonessential, depending on its effect on an organism's fitness [1] It is considered essential if its knockout results in a lethal phenotype and nonessential if the knocked-out organism is viable. Alan Wilson and colleagues proposed that the genetic rate of evolution should be dependent on gene importance, i.e., essential genes should evolve more slowly than nonessential genes [2]. This has been termed the knockout-rate (KOR) hypothesis, linking between gene functional indispensability and rate of evolution [3]. Since the publication of the KOR hypothesis, extensive research has PLOS ONE | DOI:10.1371/journal.pone.0123785 April 20, 2015
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