Tuesday, December 7, 2010

3rd Semiannual Bay Area Population Genomics Conference


The schedule for BAPG III at Stanford is all set. This time and hopefully in the future BAPG is sponsored by the Ecology and Evolution Group at the Stanford Biology Department. We have an exceptional lineup of speakers from Berkeley, UC Santa Cruz and Stanford. The meeting will start at 9AM with coffee and will end with lunch and a poster session.
9:30 AM Rachel Brem, UC Berkeley
Pathway evolution in Saccharomyces
10:00 AM Dario Valenzano, Stanford
Genetic Architecture of longevity in the short-lived fish
Nothobranchius furzeri
10:30 AM Paul Jenkins, UC Berkeley
A new approach to computing likelihoods in population genetics models
with recombination
11:30 AM Jared Wenger, Stanford
Adaptive mutations effect minimal trade-offs across the yeast adaptive
landscape
12:00 PM Ed Green, UC Santa Cruz
Recent human evolution as revealed by ancient hominin genome
sequences

For additional information (schedule, parking, registration, poster lineup), the latest news and the videos of the presentation after the conference please go to
http://www.stanford.edu/group/petrov/BAPG.html

Saturday, December 4, 2010

Broker Genes in Human Disease


Genes that underlie human disease are important subjects of systems biology research. In a paper just published in GBE by James Cai, Elhanan Borenstein and Dmitri, we demonstrated that Mendelian and complex disease genes have distinct and consistent protein–protein interaction (PPI) properties. Disease genes have unusually high degree (number of connections to other proteins) and low clustering coefficients (their neighbor proteins tend not to be connected). We describe such genes as brokers in that they connect many proteins that would not be connected otherwise. In contrast, disease genes identified in genome-wide association study (GWAS) do not have these broker properties. We suggest that the mapping of the GWAS-identified SNPs onto the genes underlying disease is highly error prone. This research can be used to help improve this mapping and prioritize the identification of disease genes in GWAS studies.

Saturday, October 2, 2010

Universal patterns of mutation

Natural selection sorts through the variability generated by mutation and biases evolution toward fitter outcomes. Mutation, while generally agnostic to fitness can also bias evolutionary outcomes because certain types of mutations occur more frequently than others. For instance, it was generally assumed that the extreme variation observed in nucleotide content among bacteria (from ~20% to ~80% GC) is predominantly driven by extreme differences in mutational biases between different bacterial lineages. Under such an assumption, mutation would have to be strongly AT-biased in some lineages and strongly GC-biased in others. In sexually reproducing organisms mutational biases can be investigated by examining low frequency polymorphisms. In bacteria, however, this has not been possible because the concepts of species and polymorphism are ill-defined. In a paper recently published in PLoS Genetics, Ruth Hershberg and Dmitri Petrov demonstrated that bacterial lineages that recently developed clonal, pathogenic lifestyles evolve under extremely relaxed selection, and are uniquely suitable for the study of bacterial mutational biases.  We analyzed large sequence datasets from five clonal pathogens in four diverse bacterial clades spanning most of the range of genomic nucleotide content. Contrary to expectations they found that mutation is AT-biased in every case to a very similar degree. Furthermore in each case mutation is dominated by transitions from C/G to T/A. These findings demonstrate that mutational biases are far les variable than previously assumed and that variation in bacterial nucleotide content is not due entirely to mutational biases. Rather natural selection or a selection like process such as biased gene conversion must strongly affect nucleotide content in bacteria. A paper by Hildebrand and colleagues published back-to-back to ours inthe same issue of PLoS Genetics reached similar conclusions: Evidence of Selection upon Genomic GC-Content in Bacteria. PLoS Genetics also published a commentary on this work by Eduardo Rocha and Edward Feil: Mutational Patterns Cannot Explain Genome Composition: Are There Any Neutral Sites in the Genomes of Bacteria?

Thursday, August 19, 2010

Physics of Evolution

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Dmitri is going to present two lectures at the "Physics of Evolution" workshop at UC San Diego at the end of this month. The workshop is dedicated to the applications of statistical physics to quantification of evolutionary process. The organizers say that:"This summer school will introduce graduate students and postdoctoral researchers in the fields of biological physics, statistical mechanics and non-equilibrium processes to the opportunities and challenges present in the area of Darwinian evolutionary dynamics. These have been enabled by sequencing technology advances, a new generation of quantitative laboratory-scale experiments, and new concepts in theoretical approaches to complex systems. Topics to be covered include: modern genomics tools, microorganism experiments, mutation-selection theory, the role of recombination and horizontal gene transfer, and applications to both the immune system and to infectious disease". Dmitri will talk about two papers: (1) one about our recent finding that Drosophila appears to have such large effective population sizes that adaptation is not limited by mutation and (ii) one on the recent work of a postdoc in the lab, Ruth Hershberg,that mutation appears to be always biased towrads A's and T's across all bacteria potentially implying that GC-rich bacterial genomes are under selection to be GC rich. The paper about Ruth's work is about to come out in PloS Genetics.

Thursday, July 29, 2010

James Cai is a new Assistant Professor at Texas A&M!

We are very happy to announce that James Cai, a postdoctoral fellow in the lab, has accepted an offer for a tenure-track Assistant Professor position at Texas A&M University, Department of Veterinary Integrative Biosciences. He will be moving in September and is already starting to build a computational genomics laboratory there. (See the ad for a postdoctoral position in James's new lab.) His group will focus on computational research in population genomics and molecular evolution, applying population genetic theory to modern biological data and developing statistical tests and computational tools to investigate evolutionary processes shaping genome variability patterns within and between species. James joined our lab in 2006 after the completion of his Ph.D. at the University of Hong Kong. Viola Luo, James's wife pictured above, moved from Hong Kong to the Bay Area and joined James at Stanford in 2007, where she started her career in regulatory affairs of clinical trials at Stanford Cancer Center. In our lab, James focused on understanding how positive selection shapes patterns of polymorphism in the human genome and published a key paper that showed for the first time that positive selection is indeed pervasive in the human genome and does leave the expected signatures in the patterns of polymorphism. See the description of this research in Stanford Daily. James was also interested how the timing of the gene's entry into the genome (gene age) interacts with the gene's importance to the functioning of the organism and the way natural selection shapes its evolution. He published a series of papers on this topic as well. Finally, James is famous for creating a set of Matlab based toolkits for population genetics and molecular evolution. We are all extremely proud of James and wish him the best of luck in his brilliant young career!

Tuesday, July 13, 2010

Every mutation, at every site, at any given time

imageAdaptation in eukaryotes is often assumed to be limited by the waiting time for adaptive mutations. This is because effective population sizes are believed to be relatively small, typically on the order of only a few million reproducing individuals or less. It should therefore take hundreds or even thousands of generations until a particular new mutation emerges. However, several striking examples of rapid adaptation appear inconsistent with this view. In a paper just published by PloS Genetics, we (co-first authors Talia Karasov and Philipp Messer, and Dmitri) investigate a showpiece case for rapid adaptation, the evolution of pesticide resistance in the classical genetic organism Drosophila melanogaster. Our analysis reveals distinct population genetic signatures of this adaptation that can only be explained if the number of reproducing flies is, in fact, more than 100-fold larger than commonly believed. We argue that the old estimates, based on standing levels of neutral genetic variation, are misleading in the case of rapid adaptation because levels of standing variation are strongly affected by infrequent population crashes or adaptations taking place in the vicinity of neutral sites. We suggest that much of the time adaptation in Drosophila takes place in populations that are much larger that a billion meaning that every single-step mutation at every site exists in the population at every given time. This means that soft sweeps should be very common and that complex, multi-step adaptations should fix all at once without intermediate fixations of single-step mutations. We also argue that adaptation should be not mutation-limited in all species with population sizes that exceed a billion (roughly the inverse of mutation rate per site), which is the case for many insects and most marine invertebrates. Nick Barton wrote a great perspective article and the work was also highlighted in Nature Review Genetics and Faculty of 1000. It is currently in the top 10 most viewed articles on Faculty of 1000 and in PLoS Genetics.

Sunday, April 25, 2010

Nadia Singh is the newest Assistant Professor in the Genetics Department at NC State

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Nadia Singh, a former PhD student in the lab, has accepted an Assistant Professor position in the Genetics Department at the North Carolina State University. Nadia received her PhD from Stanford in 2006, and went on to a postdoctoral position at Cornell University in the labs of Andy Clark and Chip Aquadro. Nadia will begin her new position at NCSU in the Fall of 2010. NCSU has a wonderfully rich community with a strong emphasis on molecular, quantitative, developmental, computational, and statistical genetics, and Nadia is looking forward to continuing her work on mutation and recombination rate variation in Drosophila in this new and interactive environment. Nadia is the first lab graduate student to start her own lab. We are all extremely proud and wish Nadia the best of luck!

Friday, April 9, 2010

Adaptation to temperate climates in Drosophila

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The potential of geographic studies of genetic variation for the understanding of adaptation has been recognized for some time. In Drosophila, most of the available studies are based on a priori candidates giving a biased picture of the genes and traits under spatially varying selection. In a paper just published in PLoS Genetics and led by Josefa Gonzalez, we performed a genome-wide scan of adaptations to temperate climates associated with Transposable Element (TE) insertions. We integrated the available information of the identified TEs and their nearby genes to provide plausible hypotheses about the phenotypic consequences of these insertions. Considering the diversity of these TEs and the variety of genes into which they are inserted, it is surprising that their adaptive effects are consistently related to temperate climate-related factors. The TEs identified in this work add substantially to the markers available to monitor the impact of climate change on populations.

Monday, March 1, 2010

Philip Bulterys is accepted to UCLA MD/PhD program!

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Philip Bulterys, a fourth-year undergraduate in the lab, was just accepted into the extremely prestigious UCLA MD/PhD program (MSTP). Philip grew up in pre-genocide Rwanda and attended high school in Lusaka, Zambia. His parents are both medical epidemiologists and Philip became interested in public health at an early age. As a high school student he volunteered in the malnutrition ward of the University Teaching Hospital, initiated a street-kids project with friends, and conducted a microbial water quality study to look for fecal coliforms in a local community’s drinking water. He has also participated in the emergency response to the HIV epidemic - the response partly led by Philip's parents. He is firmly and passionately committed to public health and understanding, preventing, and curing infectious disease. Philip is currently working on an HIV evolution project and hopes to continue studying the evolution and transmission of infectious diseases throughout his training and career. We are all extremely proud and extend our congratulations for an honor and an opportunity that is so richly deserved.

Wednesday, February 17, 2010

Fabian Staubach is joining our lab in May 2010!

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Fabian Staubach from the Max Planck Institute for Evolutionary Biology is joining our lab in May 2010! During his Ph.D. research he worked on the evolution of gene expression in natural populations of house mice (Mus musculus) and found a de novo originated gene in the mouse lineage. Currently he is finishing his work on a 600k mouse genotyping array applied to natural populations and a metagenomics 454 sequencing project on the gut flora of mice. For his research he applied and developed a variety of molecular biology, statistical, and bioinformatics tools to shed light on transcriptional evolution, mouse population genetics and the evolution of new genes. Fabian will work on natural selection and adaptation in Drosophila.
For more information please go to: http://www.evolbio.mpg.de/english/people/staff/wissPersonal/wissM19/index.html

Monday, February 1, 2010

Second Bay Area Population Genomics Conference

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On the heels of the success of the first Bay Area Population Genomics Conference at Stanford in the Fall 0f 2009 we are planning the second BAPG Conference at Berkeley on March the 13th. The labs of Doris Bachtrog, Michael Eisen, and Rasmus Nielsen are going to take the lead in organizing. Students and faculty from Stanford, Berkeley, UCSF, and UC Davis will be represented.

If you want to receive updated news about the BAPG conference please join
http://groups.google.com/group/bayareapopulationgenomics

The PI's should also join: http://groups.google.com/group/bay-area-population-genetics/

Wednesday, January 13, 2010

Alan Bergland is joining the lab

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We are excited that Alan Bergland from Brown University has decided to join our lab! Alan is currently finishing up his Ph.D. research (http://www.brown.edu/Departments/EEB) which focused on understanding the interplay between environmental variation and both long- and short-term evolutionary processes. Specifically he studied the relationship between larval nutrition and adult fecundity in Drosophila melanogaster. This research used an impressive array of tools and concepts from evolutionary demography, ecology, molecular and quantitative genetics, and physiology to investigate how life history plasticity evolves in natural populations. Alan will arrive in September 2010 and will focus on the population and molecular genetics of local adaptation in Drosophila.