Jan 27th, Roy Ronen: Learning Natural Selection from the Site Frequency Spectrum

Roy Ronen, UCSD

Roy Ronen, UCSD

Genetic adaptation to external stimuli occurs through the combined action of mutation and selection. A central problem in genetics is to identify loci responsive to specific selective constraints. Many tests have been proposed to identify the genomic signatures of natural selection by quantifying the skew in the the site frequency spectrum (SFS) under selection relative to neutrality. We build upon recent work that connects many of these tests under a common framework, by describing how selective sweeps impact the scaled SFS (and cross-population SFS). We show that the specific skew depends on many attributes of the sweep, including the selection coefficient and the time under selection. Using supervised learning on extensive simulated data, we characterize the features of the scaled SFS that best separate different types of selective sweeps from neutrality. We develop a test, SFselect, that consistently outperforms many existing tests over a wide range of selective sweeps. Applying SFselect to variation data from a laboratory evolution experiment of Drosophila melanogaster adapted to hypoxia, we identify loci that strengthen the role of the Notch pathway in hypoxia tolerance, but were missed with previous approaches. Finally, we discuss the challenges and possibilities of learning to identify soft selection (e.g. on the standing variation) and distinguish it from classic hard selective sweeps.

About Roy

Roy Ronen is a PhD candidate in the Bioinformatics and Systems Biology program at University of California, San Diego. He works with Dr. Vineet Bafna on the application of statistical learning and discrete algorithms to population genetics. Before this, he completed his undergraduate degree in computer science at Ben-Gurion University in Israel, and worked at Tel Aviv University’s high-throughput sequencing facility as a software developer. Roy is interested in the theory and application of methods for identifying mechanism of genetic adaptation.

Seminar details

Monday Jan 27th, 2014

12:45 PM Lunch: sign up sheet here. Come early for lunch, because we cannot take food into the seminar room!

1:15 PM Seminar starts.

Location: Munzer Hall (after Li Ka Shing on the medical campus)

Host: Carlos Bustamante

Schedule: Rosario Monge (rmonge at stanford.edu)

Jan 22nd, Yang Li: Use of alternative micro-exons in the developing brain

Yang Li, Oxford University

Yang Li, Oxford University

Less than 5% of all annotated internal exons are 51bp or shorter (micro-exons). The sharp decline in the number of exons of decreasing sizes below 51bp suggests that micro-exons are strongly disfavoured, possibly because the splicing machinery struggles to detect or splice out introns flanking short exons. Surprisingly, over a thousand micro-exons have been annotated within human genes, yet their functional roles have largely been overlooked. I will discuss my work on identifying the roles of micro-exons with a particular focus on micro-exons expressed during human brain development. I will also describe putative regulatory mechanisms that are able to control the usage of these micro-exons in a context-specific manner. Additionally, I will present a simple strategy that allows the discovery of novel micro-exons from next-generation sequencing data, which complements general de novo exon discovery tools such as Cufflinks.

About Yang

At the end of his maths and computer science undergraduate degree at McGill, Yang started to discover biology as a new interest. Fascinated by ageing and the large differences in life expectancy across animals, he started to work on the comparative biology of ageing, first during a summer internship in George Church’s lab at Harvard Medical School, and then as a MPhil project at the University of Liverpool under the supervision of Joao Pedro de Magalhaes. He later moved to the University of Oxford for his PhD to study comparative genomics with Richard Copley and Chris Ponting. In Oxford, Yang made major contributions to the genome and transcriptome analysis of five East-African cichlids and also of the hyperthermophile worm paralvinella sulfincola. He also participated in the study of the painted turtle and bowhead whale genomes. Currently, he is investigating gene architecture evolution with particular emphasis on alternative splicing regulation.

Seminar details

Wednesday Jan 22nd, 2014

12:45 PM Lunch: sign up sheet here. Come early for lunch, because we cannot take food into the seminar room!

1:15 PM Seminar starts.

Location: Munzer Hall (after Li Ka Shing on the medical campus)

Host: Jonathan Pritchard

Schedule: Tara Trim (ttrim at stanford.edu)

Nov 13th, Katharine Grabek: Transcriptome Dynamics in the Brown Adipose Tissue of a Hibernator

Obesity is a major health crisis in the United States. One novel, potential strategy in obesity treatment is the exploitation of brown adipose tissue (BAT). Hibernating mammals are excellent natural models for studying this tissue, because they are dependent upon BAT for rewarming during repeated arousal episodes and to maintain a minimum body temperature in torpor throughout the extended period of hibernation. Moreover, the tissue undergoes an annual cycle of atrophy and hypertrophy. In our current study, we characterized the transcriptomic changes that underlie the BAT phenotype in a circannual hibernator, the 13-lined ground squirrel, Ictidomys tridecemlineatus. Our results reveal that most gene expression changes are seasonal; transcripts involved in lipid metabolism dominate the period of hibernation, while those involved in apoptosis and RNA-processing dominate the period of spring homeothermy. Moreover, many of the “hibernation-increased” transcripts show an unexpected pattern – apparently increasing while in the low body temperature periods of torpor and early arousal. Upon further investigation, we find that the torpor-increased transcripts are enriched by polyadenylation rather than additional transcription. We hypothesize that polyadenylation protects essential transcripts from degradation during torpor and poises the selected subset for immediate utilization upon arousal.

Grabek_photoAbout Katharine

Katharine Grabek is a doctoral candidate in the Human Medical Genetics and Genomics Program at the University of Colorado, Anschutz Medical Campus. With Dr. Sandy Martin as her advisor, she has characterized the differentially expressed genes and proteins that underlie the extreme phenotype of mammalian hibernation. Her work is focused on two organs that must function at low body temperature: the heart and brown adipose tissue.

Seminar details

Wednesday Nov 13th

1 PM Lunch: sign up sheet here.

1:15 PM Seminar starts.

Location: Clark S361

Host: Carlos Bustamante

Schedule: Rosario Monge (rmonge at stanford.edu)