Sergey Nuzhdin

Summary Statement of Research Interests

Evolution is on the verge of a technological evolution. Our lab searches for information in vast data bases, formulates research in model-based frameworks, uses systems approaches developed in engineering, and relies on high-powered computing for statistical analyses. We are concept and question oriented – seeking out any system or data set that will help us shed light on evolutionary principles. Our past research described below has focused on mechanistic understanding of evolution of complex systems. Here I describe some of our recent advances in three main areas of research: transposable elements (TEs), quantitative genetics, and genomics. Currently and in the future, we will be focusing on incorporating network thinking in our systems analyses.

Research Keywords

population genetics
quantitative genetics
transposable elements
genomics
bioinformatics
life span
Drosophila melanogaster
Medicago truncatula
Pea aphids

Research Specialties

My work in education has three main components: i) teaching undergraduate and graduate classes, ii) advising student research, and iii) lecturing internationally. Intellect, skills, and motivation of graduate students are of great importance, as they serve as teaching assistants in undergraduate classes and immediate advisors in undergraduate research.

i) Evolution is one of the most complex subjects to teach. First, it is required for nearly all biologists. Doctors, pharmacists, biotechnologists, epidemiologists, agronomists – all have to master its concepts. However, the class content is rather remote from their narrow specialty. Some students feel little drive to learn. Second, evolution is nearly the only model-based biological class undergraduate students experience. It represents the first hard realization of practical use of equations and statistical tests. Third, the data and proofs in evolution are frequently historical – appearing less falsifiable. Many students are reluctant to accept them as rigorous. Fourth, evolution has been singled for abuse by several religions. Many students feel conflicted. With vast amounts of genomic and systems biology data, we can now teach evolution as rigorous modern science rather than a collection of historical anecdotes. Over six years of offering evolution to 150-200 students, I have been progressively developing a modern evolution class emphasizing real-life examples and experimental approaches. Unfortunately, no evolution textbook matches the rigor of cell biology or molecular genetics standards. I have developed a complete Web resource including lecture notes, numerical homework problems, and Web-based interactive tools and assays. I am now applying these tools in teaching evolutionary portion of USC Genetics class. I am also co-developing an upper level class of Advanced Evolution with Magnus Nordborg.

ii) My firm belief is that effective method of advising students is not telling them what to do. Rather, it is in helping them to unfold own curiosity. With every graduate student individually (and selected undergraduate students), I read many research papers on numerous topics suggested by a student. We brainstorm on all the interesting manuscripts and discuss where they could potentially lead. As a result, the student i) forms a vision of scientific frontiers (and I update my visions); and ii) eventually falls in love with some topics, that s(he) pursues. Passion towards a research direction added to high motivation and intelligence does the rest: motivating trainees to learn techniques, encouraging them to spend days and nights in the lab, and giving them a feeling of controlling the future of their own research. Trainees also need access to intellectual and technical expertise, including access to the best post docs. I maintain a diverse enough group to cover most areas required for rigorous research in evolution: molecular biology, bioinformatics, genomics, modeling, and statistics. Cohesion of the lab is maintained due to weekly lab meetings frequented by trainees and faculty of other labs. We discuss ideas, research plans, work in progress, and oncoming manuscripts. To alleviate stress, facilitate openness of the discussions, and make trainees speak with each other; I organize lab hiking, sailing, and mushroom collecting trips. Undergraduate students experience this atmosphere of openness and collective joy by science. My new USC lab, started 3 months ago, already enjoys a community of 4 postdocs, 5 graduate students, a technician, and several undergraduates. We receive numerous collaborators as visitors.

iii) It pains me to see the devastation in Russian science – once upon a time leading the world in mathematics and physics. Quoting : “There are good and bad news for Russian students. Good is there are plenty great Russian professors. Bad is they all work abroad”. The average age of a Professor in Moscow State University (MSU) is 61. The salary of the Department head is ~$200 a month. There are severely limited subscriptions to reputable specialty journals with only a few outdated research resources. Nearly no professors maintain active research programs. There are 20-50 biological labs in all of Russia still working at a frontier international level, with up to 100 more following their lead. Unfortunately, most of them belong to the Russian Academy of Sciences and are thus structurally divorced from Education. There are Great born-to-be-scientist students. My personal goal is to pick those interested in my areas of expertise and save them as scientists. Typically once a year, I visit Departments of Evolution and Biophysics of MSU. Over ~2 weeks, I give 16-20 different lectures and seminars and interact with undergraduate and graduate students. I am also accepting international students, including from Russia, for short term research projects in my lab. I already taught one of such classes during my tenure in USC.

Detailed Statement of Research Interests

TEs are replicating units, ranging in size from hundreds to thousands of nucleotides. They survive by spreading their sequence on host chromosomes and can account for up to 90% of the genome. In populations, TEs spread via recombination between sexual partners. How can TEs and their hosts co-exist without killing each other? Many sub-questions must be investigated: a) Do hosts control TEs, and if yes by what mechanism? b) Do TEs compromise the fitness of the host? c) If so, what are the relative deleterious effects of TE insertions, recombination between copies, and TE expression. We have a) mapped the host genes that control a model TE, copia, and showed that this control is at the post-transcriptional level; b) performed mutation-accumulation experiments to estimate how copia insertions contribute to fitness meltdown, and discovered that half transposition per genome per generation accounts for a half of overall fitness decline; c) tested whether actively expressing TE copies are selected against more strongly than dead copies, and found no evidence for this. We pioneered concepts highlighting competition among TEs as a mechanism of copy number control. This direction of our work was highlighted in The Economist.

The abundant genetic variation present in natural populations underlies adaptation and interspecific divergence. Our research on courtship song, hydrocarbon-based mating preference, sex comb number, lipid content, stress resistance, fecundity, pigmentation, and other Drosophila characters, has provided some key insights. Do very few or numerous QTLs contribute to natural genetic variation? We calculate between five and ten. What are the magnitudes of their effects? We estimate that each accounts for approximately 10% of the genetic variation. How pleiotropic are natural alleles? We find that effects are trait-limited and environment-specific. Recently, we discovered natural alleles decreasing mortality in young Drosophila at the expense of increasing death rate with advancing age. We are taking this work further to identify the causal DNA polymorphisms.

Quantitative genetics and molecular evolution have traditionally focused on genes. Recent technological (high throughput genotyping, RNA, and protein analyses) and conceptual (theoretical analyses of genetic network) advances are shifting the focus to systems of interacting genes. We have pioneered efforts to a) characterize genetic variation within species and divergence between them at the level of the whole genome transcript, b) estimate to what extent intraspecific variation is heritable, and c) elucidate what fraction of intraspecific expression variation and interspecific transcript level divergence is attributable to cis regulatory regions. For instance, by comparing genetic variation in transcription levels among D. simulans to the divergence between D. simulans and the closely related D. melanogaster, we have identified genes under strong directional selection. Further, we have shown that the proteins coded for by these genes are rapidly evolving.

The systems investigated by our lab include bacteria-plant co-evolution, fly, yeast, and mosquito speciation and experimental evolution. Semi-to-fully independent projects are lead by students and post docs.

• UCD Chancellor Fellow, 2007-2008