The González lab at the Institute of Evolutionary Biology (CSIC-UPF), which focuses on understanding how organisms adapt to the environment, is seeking a lab technician to join their research team. You can read more about this position – with a starting date around February 2017 – here.
You can read a bit about the lab’s citizen science project “Melanogaster: Catch the fly!” in this post.
And here you can see a post about a recent publication of the lab where they discovered several naturally occurring independent transposable element insertions in the promoter region of a cold-stress response gene in the fruitfly Drosophila melanogaster.
A new collaboration amongst scientists at different centres at the PRBB, with Mar Albà from the IMIM as leading author, has come up with a new mechanism for explaining the formation of de novo genes. Although commonly new genes arise by gene duplication and diversification of the copy, some genes appear in genomic regions which did not previously contain any gene, as compared with other species. How do these genes originate from nothing?
In a preprint submitted to arXiv.org the authors propose – based on transcriptomic comparisons between humans and three other mammals – that first new regulatory motifs/promoters appeared in those regions, which lead to an activation of transcription and the origin of new potentially functional genes. Alba’s group have actually identified hundreds of putative de novo genes in the human genome.
The 2nd CEXS-UPF Symposium on Evolutionary Biology that took place in November at the Barcelona Biomedical Research Park (PRBB) opens this edition of El·lipse, the park’s monthly newspaper.
Also on the topic of evolution, Salvador Carranza (IBE) tells us about his research on reptile phylogeny. Other news include new findings on senescence and embryo development, lung cancer diagnosis, ‘mini-kidneys’ created from human stem cells, the benefits of long-term breastfeeding, new molecules involved in metastasis or computational models to decipher biological problems. On a more personal note, Baldomero Oliva (UPF) tells us about his scientific career and the secret to become a good scientist: patience and stubbornness. The current-affairs debate deals with a very topical question, raised by a recent article in The Economist: is there a reliability problem in science? Find out the different opinions of four researchers at the park!
Where do we come from? Why are we the way we are? Why aren’t there any 6-legged mammals? In this short video, Yogi Jaeger, head of the Comparative Analysis of Developmental Systems lab at the Centre for Genomic Regulation (CRG) talks about his research into these and other questions.
Genome-wide association studies (GWAS) have revolutionized the field of complex disease genetics in the last six years. Many disease associations (i.e. genetic variants that increase risk for a specific disease) have been detected using this technique, but the reported variants tend to explain only small fractions of risk. Also, the causal variants that generate the associations unveiled by GWAS have not been identified. And their frequency and degree of sharing across different ethnical populations remains unknown.
Arcadi Navarro, from the Institute of Evolutionary Biology (UPF-CSIC), set out to study the degree of sharing of disease-associated variants across populations, in order to help solving these issues. Together with Urko Marigorta, they did a comprehensive survey of GWAS replicability across 28 diseases. As they report in their paper in PLOS Genetics, most loci and SNPs discovered in Europeans for these conditions had been extensively replicated using peoples of European and East Asian ancestry, while replication with individuals of African ancestry proved to be much less common.
The authors found a strong and significant correlation across Europeans and East Asians, indicating that underlying causal variants are common and shared between the two ancestries and that they tend to map close to the associated marker SNPs.
They also observed that GWAS with larger sample sizes have detected variants with weaker effects but not with lower frequencies. This indicates that most GWAS results are due to common variants.
Marigorta UM, Navarro A. High Trans-ethnic Replicability of GWAS Results Implies Common Causal Variants. PLoS Genet. 2013 Jun;9(6):e1003566
An interview published in Ellipse, the monthly magazine of the PRBB.
Mar Albà is a biologist who has moved from the lab to the computer and the analysis of the genome. After five years in England, she joined the UPF with a Ramon y Cajal contract, and since 2005 she is an ICREA Research Professor. Currently she coordinates the group of Evolutionary Genomics at the GRIB (IMIM/UPF) and the subject ‘Principles of Genome Bioinformatics’ at the master of Bioinformatics at the UPF. Since several months she has added motherhood to those tasks.
What memories do you have from your PhD?
It was a good experience, but I did see that I was not made for the laboratory but for a more theoretical research.
How did you decide to do bioinformatics?
It was somewhat by chance. When I arrived at University College London in 1997, I didn’t know where to direct my career. I joined a Master’s degree in bioinformatics and molecular modelling, and it was decisive.
What fascinates you most about your research?
Trying to figure out how organisms evolve using the tracks present in the DNA sequence. Understanding how our genes have originated and how, during evolution, certain sequences happen to have an important role that natural selection is responsible for preserving. We do this indirectly by comparing the genomes of different species and trying to infer what may have happened on the way.
What have been the highlights of your career?
The studies I made in London in the late 90s about the evolution of repetitive sequences in the laboratory of John Hancock, the first one to use data from the complete genome of yeast. Also the research on the origin and evolution of genes that have recently appeared, which I have done in collaboration with José Castresana and Macarena Toll-Riera, indicating that these genes have an evolutionary plasticity that will be lost over time.
What are the differences in the way of doing research in London?
There weren’t big differences in the quality of research, but it was a more open, more American system, where the merits of the person are what counts, and not their origin or who they know. In fact, many group leaders were foreigners. This surprised me a lot because when I did my PhD in Barcelona, there weren’t even any foreign researchers. Things are changing now with centres like the PRBB, the CNIO or the Parc Cientific, which try to adopt a different philosophy in recruiting and which, being new, don’t suffer from certain inertia.
Is informatics a male area?
Yes, but so are other sciences. In fact, I think the working world is designed for people with few family responsibilities, which traditionally have been men. We must also take into account the instability of the research career and the continuity you need in a system where assessment is done through the production of publications and attendance at conferences. Difficult to assume if you have kids.
How can it change?
Perhaps when more women are in positions of decision, since they have a broader vision. And it’s not just a question of children, but also other aspects of a person’s life, such as caring for the elderly.
What advice would you give to junior researchers?
Do not be discouraged. At times when you doubt about your research, remember that it is a privilege to live off what you love.
What would you be if you were not a scientist?
I never thought I would do something else other than research. I never had a plan B.
What is a virus?
We used to think we knew. Before we discovered giant viruses, size was central to the definition of a virus: 0.3 micrometer filters were used to isolate microorganisms, and anything smaller than that which was infectious, was a virus.
So giant viruses were a bit of a surprise?
We discovered them by mistake. No biologist studying viruses could have discovered them, because the first thing they did was to discard anything that wasn’t filtered. We were working on intracellular parasitic bacteria when a 10-year old water sample arrived at our laboratory. It was thought to have been the cause of a pneumonia outbreak, but nobody had yet been able to isolate the microorganism responsible. Someone at our lab had the idea to use electron microscopy and there it was! It was infecting an amoeba but it didn’t look like a bacterium, although it was really big.
How big are giant viruses?
They can be 30 times bigger than the average virus, up to 750 nm. You can even see them with a light microscope! And their genome is larger than that of many bacteria. When we sequenced the mimivirus we were also surprised to see it was genetically very complex. It has 1018 genes, including many related to translation. These are not supposed to be present in viruses, since viruses use the host machinery to translate their genome into proteins.
That must have been a shock.
It was revolutionary, and it raised a lot of questions. With such complexity, could we still say that viruses are not alive? Recently researchers have found the first virus that can be infected by another virus – I say, if you can get sick, you are very definitely alive!
How do giant viruses change our view of evolution?
They are very old and the genomic analysis of marine viruses shows that they are very common and probably major players in the ecology. Although they are different from other viruses, if one analyses their evolutionary relationships, giant viruses fit perfectly with other viruses. However, they also have things in common with bacteria, such as the structure of the capsid, as well as with eukaryotes.
They are a real mix then?
My controversial theory is that DNA was invented by viruses to protect themselves from their host, an RNA cell. Slowly, the cell took that DNA machinery and incorporated it, and the nucleus was formed. At the same time, the viruses started to lose some of those genes that the cell had incorporated. After several cycles of infection, the cell gradually increased its complexity and the viruses reduced their genome.
Have we seen it all?
I think we will find bigger viruses, with more translation genes. One day we will have a real problem defining a virus!
Pygmies, everyone knows, present the lowest height among humans – adult men grow to less than 150 cm. One can find pygmy populations not only in Africa, but also in Australia, Brazil and several countries in Asia. The fact that populations in such diverse locations all have short stature in common suggests the presence of strong selective pressures on this phenotype, but this has never been proved. David Comas and colleagues from the Institute of Evolutionary Biology (IBE: CSIC-UPF) have recently published in the journal Human Genetics the first genetic hint of adaptive evolution in the African Pygmy phenotype.
They have developed a novel approach to survey the genetic architecture of phenotypes, one in which the genetic analysis also incorporated environmental variables to understand local adaptation. They have applied it to study the genomic covariation between allele frequencies and height measurements among Pygmy and non-Pygmy populations. The results show that the genomic regions that most likely participate in the genetic architecture of the phenotype, are those associated to bone homeostasis and skeletal remodeling, which could therefore be a key biological process underlying the Pygmy phenotype. They have also proved that these regions have most likely evolved under positive selection. These results are consistent with the independent emergence of the Pygmy height in other continents with similar environments, and support the putative adaptive role of the short stature of Pigmies.
David Comas’ group on Human Genome Diversity has also recently studied another very particular ethnic group, that from the Basque country in Spain. The Basque people have received considerable attention from anthropologists, geneticists and linguists during the last century due to the singularity of their language and to other cultural and biological characteristics. But any attempt to address the questions of their origin, uniqueness and heterogeneity has suffered from a weak study-design where populations were not analyzed in an adequate geographic and population context. In their last paper, published in Molecular Biology and Evolution, the group has tried to solve that by analyzing the Y chromosome and mitochondrial DNA of ∼900 individuals from 18 populations, including some where Basque is currently spoken and others where Basque might have been spoken in historical times.
The results indicate that Basque-speaking populations are similar to geographically surrounding non-Basque populations, and that their genetic uniqueness is based on a lower amount of external influences compared to other Iberians and French populations. The rough overlap of the pre-Roman tribe location and the current dialect limits supports the notion that the environmental diversity in the region has played a recurrent role in cultural differentiation at different time periods.
Mendizabal I, Marigorta UM, Lao O, Comas D. Adaptive evolution of loci covarying with the human African Pygmy phenotype. Hum Genet. 2012 Mar 11
Martínez-Cruz B, Harmant C, Platt DE, Haak W, Manry J, Ramos-Luis E, Soria-Hernanz DF, Bauduer F, Salaberria J, Oyharçabal B, Quintana-Murci L, Comas D, the Genographic Consortium. Evidence of pre-Roman tribal genetic structure in Basques from uniparentally inherited markers. Mol Biol Evol. 2012 Mar 12;