Bacterial DNA Uptake Sequences Can Accumulate by Molecular Drive Alone

Abstract

Uptake signal sequences are DNA motifs that promote DNA uptake by competent bacteria in the family Pasteurellaceae and the genus Neisseria. The genomes of these bacteria contain many copies of their canonical uptake sequence (often .100-fold overrepresentation), so the bias of the uptake machinery causes cells to prefer DNA derived from close relatives over DNA from other sources. However, the molecular and evolutionary forces responsible for the abundance of uptake sequences in these genomes are not well understood, and their presence is not easily explained by any of the current models of the evolution of competence. Here we describe use of a computer simulation model to thoroughly evaluate the simplest explanation for uptake sequences, that they accumulate in genomes by a form of molecular drive generated by biased DNA uptake and evolutionarily neutral (i.e., unselected) recombination. In parallel we used an unbiased search algorithm to characterize genomic uptake sequences and DNA uptake assays to refine the Haemophilus influenzae uptake specificity. These analyses showed that biased uptake and neutral recombination are sufficient to drive uptake sequences to high densities, with the spacings, stabilities, and strong consensuses typical of uptake sequences in real genomes. This result greatly simplifies testing of hypotheses about the benefits of DNA uptake, because it explains how genomes could have passively accumulated sequences matching the bias of their uptake machineries.

Natural Transformation of Gallibacterium anatis

“…The count function in SeqinR was used to determine the occurrences of each k-mer in each genome (k ϭ 9 in the analyses shown), and these values were normalized to densities per kilobase. The Gibbs motif sampler (37) was used to search the complete genome sequence of G. anatis UMN179 (18) for abundant motifs as described by Maughan et al (27), using the prior settings described for H. influenzae.…”

Natural Competence and the Evolution of DNA Uptake Specificity

“…The commonly assumed mate recognition function requires that both components evolve simultaneously by natural selection operating on their combined effects, but relaxing this assumption greatly simplifies the evolutionary steps. Here we first consider how-regardless of whether or not recombination is a selected function of competence-uptake bias causes a "molecular drive" leading to accumulation of uptake sequences in genomes, in the same way that biased gene conversion causes a molecular drive leading to allele fixation in sexual eukaryotes (91,101,119). We then consider how weak uptake biases could be amplified over time.…”

“…6): at any position in the genome whose sequence is not already well matched to the uptake bias, random mutation will sometimes create variants that better fit this bias, and cell death will create a pool of environmental DNA that includes this variation. Competent cells will then preferentially take up those DNA variants that better match their bias, and recombination of these with their chromosomal homologs will transfer these preferences into the genome (91). The preferred sequences need not be functionally beneficial in any way; their accumulation will inevitably continue until it is limited by mutational degradation of uptake sequences and by selection against uptake sequences that conflict with genetic functions.…”

“…The preferred sequences need not be functionally beneficial in any way; their accumulation will inevitably continue until it is limited by mutational degradation of uptake sequences and by selection against uptake sequences that conflict with genetic functions. In simulations, the mutation and transformation rates determine the final density of uptake sequences, the uptake bias determines their sequence distribution, the sizes of available DNA fragments determine their spacing, and natural selection determines their relationships to protein coding and other genome functions (91). Molecular drive is also predicted to prevent accumulation of uptake-reducing mutations once strong uptake sequences have arisen.…”

“…Genetics [91] with permission of the publisher; permission conveyed through Copyright Clearance Center, Inc.). Large circles, strongly preferred sequences; small circles, weakly preferred sequences.…”