Tutorial

Papers that will be discuss between March and May 2012 : When and where? : On Fridays at 12:15, room 4311 of the Biophore Friday March 2ndThe genome of the green anole lizard and a comparative analysis with birds and mammals Afoldietal, Nature 2011 Friday March 9thBayesian inference of ancient human demography from individual genome sequences Gronau etal, Nature Genetics 2011 Friday March 16thCryptic genetic variation promotes rapid evolutionary adaptation in an RNA enzyme Hayden etal, Nature, 2011 Friday march 30thMouse genomic variation and its effect on phenotypes and gene regulation Kean etal, Nature 2011 Friday April 20thDistinct signatures of diversifying selection revealed by genome analysis of respiratory tract and invasive bacterial populationsShea etal, PNAS 2011 Friday April 27thAn Aboriginal Australian Genome Reveals Separate Human Dispersals into Asia Rasmussen etal, Science 2011 Friday May 11thRapid Evolution of Enormous, Multichromosomal Genomes in Flowering Plant Mitochondria with Exceptionally High Mutation RatesSloan etal, Plos Biol 2012 Friday June 1st May 25thThe Molecular Diversity of Adaptive ConvergenceTenaillon etal, Science 2012

Since we used the blog format to conduct this journal club, the whole world was able to enjoy the fruits of our work. So did they come? Well, yes, there were quite a few more readers than would have attended a classical journal club: And although most visitors were from Switzerland, many came from elsewhere: There is clearly a skewed distribution of the readership of the different posts. It is unclear what is the cause, but in part it seems to be the titles, and in part the speed with which it was picked up by researchblogging.org. Indeed, we were quite visible at researchblogging.org, which aggregates science blog posts. We totaled 1730 views on that website, and it is our main source of visitors. So overall, an enjoyable experience, which we will repeat this spring. Aiming for tens or thousands of visitors, of course. I thank all the students who played the game, and wrote excellent blog posts, adapting to this unusual requirement for a PhD student.

Plasmodium falciparum parasite spreads rapidly and widely, if it is out of control. The major prevention is antimalarial drugs. However, drug resistance in parasites has evolved and spread rapidly. In consequence, it’s necessary to launch genome-wide association studies of parasite traits. Previous studies show that mutations in MAL7P1.27 (also known as pfcrt, the gene encoding the P. falciparum CQ resistance transporter) and in the genes encoding P. falciparum dihydrofolate reductase (pfdhfr) and P. falciparum dihydrofolate reductase (pfdhps) have been shown to confer resistance to CQ and SP. Moreover, copy number and/or point mutations at pfmdr1 on chromosome 5 linked to the parasite response to MQ, QN, ART and other antimalarial drugs. Additionally, it has been shown that using 342 genome-wide microsatellite markers and 92 parasite isolates collected from different parts of the world is a more efficient and less-time-consuming way to identify the chromosome segment carrying the pfcrt locus. In the present study, with increase of the number of isolated parasites, it reports the first genome-wide P. falciparum using sensitive method and GWAS of resistance of multiple antimalarial drugs. In general, the authors isolated 189 culture-adapted P. falciparum parasites in vitro culture, from Asia, Africa, America and paua New Guina. …

The investigation of parallel evolution is a powerful paradigm to study mechanisms of adaptation.  This review and opinion paper stresses the fact that although remarkable examples have been studied, molecular bases of adaptation are still poorly understood in the vast majority of cases. In rare examples, a genetic variation has been linked to repeated and independent adaptation. In the examples of Mc1r , multiple mutations occurred in the same gene independently leading to different coat colours in mice.  In humans, lactose tolerance was acquired repeatedly due to mutations occurring independently in the same genes in different populations.  In the paper, authors describe mutations in Pitx1 which have occurred repeatedly in three spine stickleback fish leading to reduced pelvic armor plate which differentiates the sea water from the fresh water specie. These observations have been validated by transgenic animals demonstrating the fact that Pitx1 is the genetic basis of this recurrent phenotype and form of adaptation. As a reader naïve to the field, I found that this paper describes well the obstacles that researchers are facing in the investigation of the molecular basis of adaptation.  Genetic data is sparse and the vast majority of species have not been sequenced. For those …

Higher throughput, better accuracy, and lower costs of DNA sequencing technology revolutionized the field of genetics. Building upon these technological advances, 1000 genomes project marked the new era of human genetics. The ambitious goal of this international project is to build a detailed map of human genetic variation by sequencing 2500 individuals from five major population groups. The first insights into the project results got available upon completion of the pilot phase that covered some hundreds of individuals (The 1000 Genomes Project Consortium 2010). Whereas sequencing costs drop, data management costs are raising. The tremendous amounts of sequencing data from thousands of genomes over 3 billion DNA base pairs raise important challenges for storage and analysis. To tackle this, EBI developed a dedicated computer platform to manipulate and share large-scale data. Furthermore, although sequencing becomes cheaper, getting the sequences of 2500 genomes remains a burden. Pilot project assessed two cost-containment strategies: low-coverage (4x) sequencing of the whole genome and high coverage (50x) sequencing of exon-targeted regions (8140 exons were included). According to pilot study, low-coverage whole genome sequencing approach performs reasonably well. Targeting multiple individuals increases the power to detect different frequency variants in the population. The number and accuracy …

Since their first appearance humans have colonized most parts of the world. They have undergone multiple adaptations to a wide range of disparate habitats, which let to the appraisal of different phenotypes. Thus, dark skin and hair, for example, is an evolutionary adaptation to protect against high amounts of radiation coming from the sun. An adaptive trait can be fixed in a population through the mechanisms of natural selection acting on point mutations or on standing genetic variation.In their article “Classic Selective Sweeps were Rare in Recent Human Evolution” Hernandez et al. 2011 were interested in the modes of natural selection that shaped human adaptations. Up to date, most studies suggest that the principal mode of adaptation is due to positive selection. Therefore, a beneficial mutation appears in a population and is getting rapidly fixed. The decrease in neutral diversity in the linked sites results in the occurrence of a ‘classic selective sweep’. Hernandez et al. 2011 were questioning whether it could be possible that not only selective sweeps but also other types of selection could have been involved in human adaptation. Resequencing data for 179 human genomes from “three” populations (African, Chinese/Japanese and European) was investigated. They assessed average …

Plasmodium Falciparum is a protozoan parasite that cause malaria in human. An estimated 781,000 people died from malaria in 2009 according to the World Health Organization. Different treatments exist against malaria since 1891 such as Atabrine, Chloroquine(CQ) or Artemisinin(ART) but there is not yet any vaccination possible and due to the evolution one can see an increasing in drug resistance of the Falciparum population. Some information at genomic level are at a high importance to determine the resistance to antimalarial drugs. To study possible treatments, a group of researchers worked on Plasmodium Falciparum to detect variation in recombination rate, loci under recent positive selection and genes associated with drug responses. For this work, the researchers used the GWAS method (Genome-Wide Association Studies) which allows to define if a single-nucleotide polymorphism (SNPs) is associated with a trait, here the malaria. The authors collected and adapted 189 independent P. falciparum: including 146 from Asia (specifically, Thailand and Cambodia), 26 from Africa, 14 from America and 3 from Papua New Guinea. Antimalarial drug resistance of Falciparum is different according to their localization, thus the choice of the authors is good but not well-balanced. Using population genetics methods and stratification methods, the authors showed …

The threespine stickleback (Gasterosteus aculeatus) is a coastal and freshwater form species that lives in marine, eustarine and freshwater habits throughout the Northern hemisphere. Previous studies suggested that the freshwater stickleback populations might have diverged independently from oceanic populations less than 10,000 years ago. Indeed, the search for new space might have caused migration to unexplored freshwater habitats. Among threespine stickleback populations, there is a huge phenotypic variation mainly due to adaptation to differences in feeding behaviours and defence mechanisms. For example, the lateral plate armor is present in oceanic populations but has been lost in many derived freshwater populations. This is of particular importance because despite little or no gene flow among freshwater populations, life history traits appear independently in populations of similar habitats. Its evolutionary history and its extraordinary phenotypic diversity made it appropriate for studying the genetic changes that underlie adaptation to new environments. Moreover, recent advances in genome biology and next generation sequencing techniques allowed addressing questions about evolutionary processes acting at a genomic scale in natural populations. In this paper (“Population Genomics of Parallel Adaptation in Threespine Stickleback using Sequenced RAD Tags”) of Hohenlohe et al. 2010 the main goal was to assess whether the …

Slightly off topic relative to the usual journal-club posts, but I think that this is relevant to understanding where we are going with genomics for studying variability: Next-Gen 101: Video Tutorial on Conducting Whole-Exome Sequencing Research from the National Human Genome Research Institute (from the Nielsen lab blog)

According to Darwin, adaptation is a gradual process. The rate of adaptation is variable and diverse whose reason is unknown. It ’s well known that genomic changes are linked with adaptation, but exact relationship remain elusive. With imperfect knowledge of organism’s genetics and complicated environment, it’s difficult to make clear conclusion. Thus, this paper designed a experiment using tractable model organisms in controlled laboratory environments, in order to minimize the confounding factors and complexity. Moreover, they sequence complete genomes to find the mutations responsible for particular adaptation. In addition, it’s possible to find out whether the dynamics of genomic and adaptive evolution are coupled very tightly or only loosely. In the first step, they sequenced the genomes of E. coli clones sampled at generations 2K, 5K, 10K, 20K and 40K. Through 20K generations , 45 mutations were identified, moreover, the number of mutational differences between accumulated in a ncestral and evolved genomes accumulated in a near-linear fashion over this period. Neutral evolution should accumulate by drift at a uniform rate and are not beneficial. However, in this experiment,they found fitness trajectory shows profound adaptation that is not linear. Particularly, the rate of fitness improvement decelerates over time indicating the rate …