Research

Magnus Nordborg

Background

One of the most important challenges facing biology today is making sense of genetic variation. Understanding how genetic variation translates into phenotypic variation and how this translation depends on the environment is fundamental to our understanding of evolution, and has enormous practical implications for both medicine and agriculture. Our group studies the genotype–phenotype map, primarily to understand evolution better. We also work directly at the sequence level, seeking to understand the forces that have shaped genomic variation within and between species. Our research is usually quantitative, with several group members doing exclusively computational work. I moved from the University of Southern California to become Scientific Director of the GMI in 2009, and our group is still split between Los Angeles and Vienna.

Joining the Nordborg Lab

We are always looking for talented new members of our group. Research in the group focuses on quantitative and population genetics of Arabidopsis, with an emphasis on genomics and computational approaches, but we also pursue theoretical questions (and work with organisms other than Arabidopsis). Group members` backgrounds vary widely, from plant molecular biology to statistics.

Prospective postdocs are expected to have at least one first-author publication in a major international journal. If you are eligible for postdoctoral fellowships (e.g., from NIH, NSF, EMBO, DFG), you are expected to be competitive for them as well as apply for them (we are happy to help). If you are interested in working with us, please send an e-mail explaining which aspect of our research you are interested in, and why. Please attach a CV and the names of three referees.

Prospective PhD students must apply through either the Vienna Biocenter International PhD Program or the Vienna Graduate School of Population Genetics. You should obviously feel free to contact me directly, but please note that I do not admit students directly into the lab (so sending general inquiries is pointless).

Prospective Diploma students and summer interns should contact me directly. Please describe your background, and which project you are interested in working on.

Genome wide association mapping in A. Thaliana

Fig. 1: GWA mapping results for flowering time (FT) in four environments. (A) Spring in Spain; (B) summer in Spain; (C) spring in Sweden; and (D) summer in Sweden. Four a priori loci (shown in red by the gray dashed lines) for FT showed significant (P ≤ 1 × 10−5) in at least one environment. Eight novel loci for seasonal FT (SFT) are shown in blue.

Thanks to decreasing genotyping costs, there is currently great interest in so-called genome-wide association studies, in which one attempts to identify genes responsible for variation simply by correlating genotype (typically in the form of single nucleotide polymorphisms) with phenotype.

The model plant A. thaliana is ideally suited for such studies in that it naturally occurs as inbred lines which can be genotyped once and phenotyped repeatedly. For several years, my group has been spearheading a multi-group effort to make genome-wide association in A. thaliana a reality. We are currently finalizing the genotyping of a set of roughly 1300 lines using close to 250000 SNPs, and are phenotyping these for as many traits as possible. Follow-up studies (by my lab, and in collaboration with others) to verify and molecularly characterize some of the identified associations are also under way (see here). One of our goals is to exhaustively describe the genetic architecture of adaptive traits such as flowering time. 

Related Publication: Li Y, Huang Y, Bergelson J, Nordborg M, Borevitz JO (2010) Association mapping of local climate-sensitive quantitative trait loci in Arabidopsis thaliana. Proc Natl Acad Sci USA 107: 21199-21204.

1001 genomes project

The use of SNPs in genome-wide associations is merely a proxy for having full sequence information, and sequencing of associated regions would in any case be necessary to identify causal sites. Given the rapidly decreasing costs of sequencing, it is clearly preferable to sequence all the lines used. In collaboration with several others, my lab is taking part in the 1001 genomes project, which aims to sequence 1000 lines of A. thaliana in addition to the reference genome. Our group is focusing on sequencing roughly 200 Swedish lines that will be heavily used in several other studies.

Genomic analysis of the genotype-phenotype map

We are a major part of an NIH-funded "Center of Excellence in Genomic Science" that aims to investigate the regulatory networks by which genetic variation leads to phenotypic variation. Our group is carrying out genome-wide expression profiling of large sets of lines under different environmental conditions, and are complementing this information with genome-wide epigenetic profiling. The goal is to integrate the resulting multi-level data to infer causal relationships.

Adaptation to the abiotic environment

Investigating the adaptive significance of any trait requires field studies. In collaboration with others, we are developing field sites in northern and southern Sweden (Figure 2) for reciprocal transplant competition experiments of both natural inbred lines and the offspring of crosses. The objective is to map the genes responsible for fitness differences, and to molecularly characterize them.

Fig. 2: A. thaliana in Sweden can be found in a variety of different habitats, including: beaches (left), meadows (centre) and cliff faces (right).

Molecular evolution of Arabidopsis

We are heavily involved in the comparative analysis of the genomes of close relatives of A. thaliana. Questions include the evolution of genome size, the effects of polyploidy or switching to selfing. For example, A. thaliana diverged from its closest relative, A. lyrata, only 5 to 10 million years ago, but at 125 Mb, the A. thaliana genome is dramatically smaller than that of A. lyrata (more than 200 Mb). We seek to understand the processes that underlie such dramatic changes. The genome sequence of A. lyrata and its comparison with A. thaliana has been published in Nature Genetics.

Watch a video of Magnus Nordborg speaking at the 2011 DOE JGI User Meeting on genome evolution in Arabidopsis.

Statistical methodology for association mapping

Our work on genome-wide association in A. thaliana has forced us to confront the problem of confounding by population structure, which is much more severe in this organism than it is in standard human case-control studies. As the costs of genotyping and sequencing continue to decrease, genome-wide association will become an obvious choice for investigating the genetics of natural variation in many species, and methodology for dealing with confounding will be crucial. We are exploring a wide range of methods for handling this problem, focusing in particular on the effect of having several major loci under selection present.

Related publication:
Long Q, Jeffares DC, Zhang Q, Ye K, Nizhynska V, Ning Z, Tyler-Smith C, Nordborg M (2011) PoolHap: inferring haplotype frequencies from pooled samples by next-generation sequencing. PLoS ONE 6:e15292.

The genetics of species differences in Aquilegia

In collaboration with Scott Hodges at UCSB, we are studying the genetics of species differences in the columbine genus Aquilegia (Ranunculaceae). This genus is an excellent example of a recent, rapid adaptive radiation and thus, offers many opportunities to study genetic changes at different stages in the speciation process. The genus is comprised of approximately 70 species that occupy a wide variety of habitats in North America, Europe, and Asia, and can differ substantially in floral morphology. Despite these differences, species are usually cross-compatible.

We have focused on two species, A. formosa and A. pubescens. The former is found in mountainous regions of western North America while the latter is restricted to the southern Sierra Nevada range. As illustrated in Figure 3, the species exhibit distinct differences in floral characters that have been shown to influence pollinator preference, thereby restricting gene flow between them. Additionally, they prefer different habitats: A. formosa populations typically occur in moist areas at lower elevations (below 3000 m), whereas A. pubescens populations are found in drier soils at higher elevations (3000-4000 m). However, the two species are highly interfertile, and form natural hybrid zones at mid-elevations.

We have demonstrated that the two species are very closely related at the genetic level, with most polymorphisms shared between the species, and little divergence in allele frequencies, and we are now trying to identify the genes responsible for the phenotypic differences through genome-wide association mapping using sequencing of pooled samples.

Related publication:
Cooper EA, Whittall JB, Hodges SA, Nordborg M (2010) Genetic variation at nuclear loci fails to distinguish two morphologically distinct species of Aquilegia. PLoS ONE 5:e8655.

Fig. 3: Two closely related species of Aquilegia. A. formosa (left) is mainly pollinated by hummingbirds, A. pubescens (right) by hawkmoths.

Population genetics of African green monkeys

The African green monkey, Cercopithecus aethiops, (also known as vervet monkey) is a common Old World monkey, spread throughout much of Africa, and introduced by humans to the Caribbean. It is also kept in large colonies for behavioral and biomedical research. We are part of an international consortium to develop genomic resources for African green monkeys through extensive sequencing and SNP typing of samples from wild-collected samples. Our primary interest is the genetics of subspecies differences across the African continent.

Gregor Mendel Institute of
Molecular Plant Biology GmbH


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