With Ben Wilson, Nandita Garud, Alison Feder and Zoe Assaf, I wrote a review paper about population genetics and drug resistance. It was a lot of fun to write this paper and I feel like I learned a lot during the process.
We wrote about drug resistance in influenza, malaria, TB, MRSA and HIV. It turns out that each of these case studies have something unique to teach us about evolution.
The paper is now out in Molecular Ecology. You can also download it here: 2015Wilson_et_al-Molecular_Ecology.
We made five short movies about the paper. Have a look at the one you are most interested in!
Nandita Garud on using genome scans to find resistance loci in malaria
MolEcolNandita from Pleuni Pennings on Vimeo.
Ben Wilson on the role of epistasis in resistance in Influenza
BenMolEcol from Pleuni Pennings on Vimeo.
Pleuni Pennings on standing genetic variation in HIV
MolEcol from Pleuni Pennings on Vimeo.
Alison Feder on clonal interference in TB
MolEcolAlison from Pleuni Pennings on Vimeo.
Zoe Assaf on the origins of the SCCmec element that causes methicillin resistance
MolEcolZoe from Pleuni Pennings on Vimeo.
After several brainstorming meetings, we decided on a new name: The CoDE Lab.
CoDE stands for Coding to understand Disease Evolution.
I am very happy with the new name!
The SFSU CoDE Lab in November of 2015. Kristof Theyss, Dasha Fedorova, Sidra Tufon, Patricia Kabeja, Farheen Ghiasuddin, Pleuni Pennings, Melissa Luk, Marton Hartl, Julia Pyko, Olivia Pham, Austin Lim and Dwayne Evans. Not in the picture: Kadie Williams.
Together with several collaborators at Stanford, I published a paper on the BioRxiv on selective sweeps in HIV. We find that when treatments didn’t work well (think AZT in the 1980s), sweeps were very soft, but with better treatments sweeps are getting “harder.” The first author on the paper, Alison Feder, has done most of the work on this paper including making all the figures (and they are cool!).
Alison F Feder, Soo-Yon Rhee, Robert W Shafer, Dmitri A Petrov, Pleuni S Pennings. 2015. More efficacious drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1. BioRxiv, doi:http://dx.doi.org/10.1101/024109
In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistant mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here we use 6,717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.
Figure 3: Drug resistance mutations are correlated with diversity reduction differently in different types of treatments. Treatment efficacy from literature review (% of patients with virologic suppression after 48 weeks) showed positive correspondence with clinical recommendation among RTI regimens (A) and PI+RTI regimens (B). DRM SE lower among the more efficacious and clinically recommended treatments among RTI treatments (C) and RTI+PI treatments (D). Mixed effect model shows significantly different slopes for NNRTI treatments versus NRTI treatments (E) and PI/r treatments versus PI treatments (F). Each line in (EF) represents the fitted decay in diversity with each DRM for a different treatment from the full mixed effects model and p-value labeling indicates the difference between the plotted full model and the null not fitting slopes separately for treatment groups.
Last week, my colleague Karen Crow and I hosted two amazing speakers from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany.
Caren Norden talked about “Using zebrafish retinal development as a model to understand the interplay of cell biology and mechanics during morphogenesis: From cells to tissue”
Nadine Vastenhouw talked about “The role of chromatin in repression and activation of the zygotic genome”
We invited colleagues and students from the Biology Department and provided lunch for everyone. There were around 70 people, most of them students.
The talks were great! Thanks, Nadine and Caren for visiting SF State!
I have 10 undergraduate and one graduate student in the lab this summer. It is fun!
I’ll soon make a page with names and pictures.
I am very excited to announce that our paper entitled: “Imperfect drug penetration leads to spatial monotherapy and rapid evolution of multidrug resistance” is out in PNAS.
Stefany Moreno-Gamez and Alison Hill are co-first authors on this paper. Both of them have contributed to every aspect of the paper.
Daniel Rosenbloom, Dmitri Petrov and Martin Nowak are the other co-authors on the paper.
Two-minute movie explains the main point of the paper
I made a short movie (2.5 minutes) to explain the main point of the paper:
A press release was posted on EurekAlert.
If you are interested to report on our paper, feel free to get in touch with one of the authors. Pleuni Pennings, Stefany Moreno and Daniel Rosenbloom are most available this week.
Pleuni Pennings is based in San Francisco (Pacific Time Zone, UTC-08:00).
My email address is firstname.lastname@example.org
Phone number: +1 617 417 7311
Stefany Moreno-Gamez is based in Groningen, The Netherlands (Central European Time Zone, UTC+01:00)
Email address: email@example.com
Daniel Rosenbloom is based in New York City (Eastern Time Zone, UTC-05:00)
Email address: firstname.lastname@example.org
The story behind the paper
I wrote a blog post for Haldane’s Sieve about how we started the collaboration that let to the paper. Here is the link.
The Gilbert S. Omenn Prize is awarded by the International Society for Evolution, Medicine, and Public Health for best article published each year on a topic related to evolution in the context of medicine and public health. The prize committee consisted this year of Sarah Tishkoff, Joe Alcock, Noah Rosenberg, and Alison Galvani. The real prize for 2014 went to, “Escape from bacterial iron piracy through rapid evolution of transferrin” by Matthew Barber and Nels Elde from the University of Utah. But my paper together with John Wakeley and Sergey Kryazhimskiy won an honorable mention :-)
Look here for the paper and here for a 3 minute explanation of the results.
Pennings PS, Kryazhimskiy S, Wakeley J (2014) Loss and Recovery of Genetic Diversity in Adapting Populations of HIV. PLoS Genet 10(1): e1004000. doi:10.1371/journal.pgen.1004000