Published this week in mBio, Jessica Hedge's new paper "Bacterial phylogenetic inference is robust to recombination but demographic inference is not" looks at a long-standing problem: why are phylogenetic trees so popular in bacterial genomics when everyone knows recombination (which is detectable in most species studied) leads to seriously misleading inference? A burst of research activity in the early 2000s showed that homologous recombination - which can result from various forms of horizontal gene transfer in bacteria - can distort phylogenetic trees and lead to false inference of positive selection and demographic growth in methods that rely on them.
In the intervening years there has been intense research in the field of population genetics into approaches that account for recombination, although the practically useful methods rely on approximations because of the inherent difficulties of learning about complex reticulated evolutionary networks that recombination generates. This has led many of my population genetics colleagues to regard - at least privately - the use of phylogenetic trees in recombining species as "bust", and the conclusions drawn from such studies as questionable. In this paper we show that this view is too simple.
Friday 28 November 2014
Friday 6 June 2014
Cheltenham Science Festival
Antibiotic Resistance Coconut Shy |
The game was more difficult than it looks, and just one visitor knocked off all five coconuts. We gave out NDM pens to the sixty visitors who managed to knock off three or more.
Microscope and Top Trumps |
Genome Evolution Dance Mat |
Outbreak Map |
Outbreak Map: We made an Outbreak Map to show the reach of our stall over the day, with visitors that scored highly on the coconut shy pushing in pins to show where they had travelled from. Had we been handing out germs instead of pens, we could have started outbreaks as far afield as Edinburgh, France and Spain, as well as a large cluster in Cheltenham and the surrounding counties.
Other research groups are representing the department throughout the week.
New paper: Mobile elements drive recombination hotspots in the core genome of Staphylococcus aureus
This week published in Nature Communications we have a new open access paper looking at what drives variability in rates of recombination (horizontal gene transfer, HGT) in the core genome of Staphylococcus aureus. HGT in the core genome is important for eliminating harmful mutations and promoting the spread of beneficial mutations, such as those that make the bacteria resistant to antibiotics.
Compared to recent work focusing on individual, highly-related strains of S. aureus, we found much higher rates of core HGT across the species as a whole. We saw that the frequency of HGT varies along the genome. At broad scales, core HGT is higher near the origin of replication, a pattern reminiscent of the one described by Eduardo Rocha and colleagues in E. coli, who hypothesized that the over-abundance of DNA near the origin during rapid growth could promote HGT.
At fine scales, we found more frequent HGT in regions of the core genome close to mobile elements. The hottest regions occurred near mobile regions called ICE6013, SCC and genomic island α. The insertion and excision of mobile elements from the genome represents a type of HGT, so our finding that nearby core regions also experience more HGT suggests there is some sort of "spill over". This idea is supported by work in Ashley Robinson's group that found similarities between ICE6013 and a class of mobile elements in Streptococcus agalactiae called TnGBS2. TnGBS2 was discovered by Phillipe Glaser's lab who showed it sometimes transfers large tracts of adjacent core material during conjugation.
Whether conjugation alone can explain the high levels of core HGT we saw in S. aureus is unclear - our results suggest there is detectable HGT even in core regions far from mobile elements. Transformation is another possible mechanism of core HGT, but S. aureus is generally thought to be naturally incapable of transformation. However, intriguing work published by Tarek Msadek and colleagues in 2012 indicates there may be cryptic mechanisms of transformation in S. aureus after all. It remains to be seen whether the relative contributions of transformation, transduction and conjugation to the long-term evolution of S. aureus can be disentangled.
Compared to recent work focusing on individual, highly-related strains of S. aureus, we found much higher rates of core HGT across the species as a whole. We saw that the frequency of HGT varies along the genome. At broad scales, core HGT is higher near the origin of replication, a pattern reminiscent of the one described by Eduardo Rocha and colleagues in E. coli, who hypothesized that the over-abundance of DNA near the origin during rapid growth could promote HGT.
At fine scales, we found more frequent HGT in regions of the core genome close to mobile elements. The hottest regions occurred near mobile regions called ICE6013, SCC and genomic island α. The insertion and excision of mobile elements from the genome represents a type of HGT, so our finding that nearby core regions also experience more HGT suggests there is some sort of "spill over". This idea is supported by work in Ashley Robinson's group that found similarities between ICE6013 and a class of mobile elements in Streptococcus agalactiae called TnGBS2. TnGBS2 was discovered by Phillipe Glaser's lab who showed it sometimes transfers large tracts of adjacent core material during conjugation.
Whether conjugation alone can explain the high levels of core HGT we saw in S. aureus is unclear - our results suggest there is detectable HGT even in core regions far from mobile elements. Transformation is another possible mechanism of core HGT, but S. aureus is generally thought to be naturally incapable of transformation. However, intriguing work published by Tarek Msadek and colleagues in 2012 indicates there may be cryptic mechanisms of transformation in S. aureus after all. It remains to be seen whether the relative contributions of transformation, transduction and conjugation to the long-term evolution of S. aureus can be disentangled.
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