meeting program

[Dmitri Petrov]

Dear All--

The first Bay Area Population Genomics meeting is taking shape!

The meeting will take place at Stanford. Talks will be at the Clark
Auditorium in the Clark Center.

Directions: You can find directions at http://ucomm.stanford.edu/cgi-bin/map/
by typing in Clark Center as the name of the building. The Clark
Auditorium is in the courtyard of the Clark Center.

Driving is easiest. You can also take Caltrain and then either walk to
campus (~20 minutes) or take a free Marguerite shuttle (http://
transportation.stanford.edu/marguerite/MargueriteSched.shtml#map)
(take A shuttle to get very close to Clark Center).

Parking: Parking is free on weekends at almost all parking lots. Make
sure that the sign says so though.

Schedule: We are planning to start at 9:15 AM with the breakfast
(coffee and pastries). The talks will start at 10AM. We will have five
talks (see below). We are also hoping to have a poster session
combined with lunch. If you are planning to put a poster please put
your name and the title into

http://spreadsheets.google.com/ccc?key=0AmibR2Ms8xtodDB3S1ByamszemR1dmpabVBtVWV6WFE&hl=en

and plan to arrive enough before 10 so that you have time to put it
up.

Important:

1. Please make sure that your lab has put in the correct head count
into the google excel sheet.

http://spreadsheets.google.com/ccc?key=0AmibR2Ms8xtodGpra3RyQmNibGVIQWVLeWNaTXFIZ2c&hl=en

We are buying food for breakfast/lunch and want to make sure we get
enough.

2. Please let me know by Thursday at the latest whether you are giving
a poster by adding your name, your position, which lab you are from,
and the title into this google excel sheet:

http://spreadsheets.google.com/ccc?key=0AmibR2Ms8xtodDB3S1ByamszemR1dmpabVBtVWV6WFE&hl=en

I will order poster boards on Thursday and need to have the right
count.

Hope to see you all on Saturday! Dmitri

Program:

9:15-10AM Breakfast

10-10:45AM Graham Coop, UC Davis, Graham Coop Lab, " "Meiotic
recombination hotspots in humans and mice"

10:45-11:30AM Dan Kvitek, Stanford, Gavin Sherlock Lab, "Molecular
characterization of the fitness landscape in asexually evolving
populations of Saccharomyces cerevisiae "

11:30-12:15PM David Goode, Stanford, Arend Sidow Lab, "Evolutionary
constraint facilitates interpretation of genetic variation in
resequenced human genomes"

12:15-1PM Qi Zhou, Berkeley, Doris Bachtrog Lab, "Deciphering neo-sex
and B chromosome evolution by the complete genome of Drosophila
albomicans"

1PM-1:45 Hunter Fraser, Stanford, Hunter Fraser Lab,
"Widespread adaptive evolution of gene expression in budding yeast"

1:45 - whenever Lunch + posters

Abstracts:

Graham Coop, UC Davis, Coop Lab " "Meiotic recombination hotspots in
humans and mice"
Abstract: Meiotic recombination events cluster into narrow regions of
the genome (1-2Kb), defined as hotspots, the molecular basis of which
remain unknown. These hotspots are known to differ in location within
and between species. I'll outline our work to identify the genetic and
molecular causes of this variation.

Dan Kvitek, Stanford, Gavin Sherlock Lab, "Molecular characterization
of the fitness landscape in asexually evolving populations of
Saccharomyces cerevisiae "

Abstract: Using fluorescent markers, we have visualized the population
dynamics of yeast evolving asexually in a glucose-limited environment,
in eight independent populations. Our data show that adaptive
evolution under these conditions does not occur by clonal replacement,
and that an adaptive event is typically not built upon the previous
one. From one of these evolving populations, we have isolated
adaptive clones from throughout the evolution and used Solexa
sequencing to identify the underlying mutations. The PKA-dependent
and independent glucose-signaling pathways are frequent targets of
adaptive mutation under these conditions, with three independent
nonsense mutations occurring in MTH1 (which encodes a repressor of
hexose transporter genes), three independent amplifications of HXT6/7
(which encodes a high affinity hexose transporter), and mutations in
three different genes whose products function in the Ras-cAMP/PKA
pathway (which integrates nutrient signaling with cell division).
Additionally, we find that the MTH1 and HXT6/7 mutations are mutually
exclusive, as they never co-occur in the same clone, and when forced
to co-occur, produce a severe fitness disadvantage. This mutual
exclusivity is an example of sign epistasis, and may be a determinant
of the evolutionary trajectory on this limiting-glucose fitness
landscape. These data provide the most detailed molecular
characterization of an experimental evolution to date, and show a
strong candidate for evolutionary trajectory-determining mutations.

David Goode, Stanford, Arend Sidow Lab, "Evolutionary constraint
facilitates interpretation of genetic variation in resequenced human
genomes"

Abstract: We here demonstrate how comparative sequence analysis
facilitates genome-wide base-pair level interpretation of individual
genetic variation, and address two questions of importance for human
personal genomics: First, whether an individual’s functional variation
comes mostly from noncoding or coding polymorphisms; second, whether
population-specific or globally present polymorphisms contribute more
to functional variation in any given individual. Neither has been
definitively answered by analyses of existing variation data because
of a focus on coding polymorphisms, ascertainment biases in favor of
common variation, and a lack of base-pair level resolution for
identifying functional variants. We resequenced 575 amplicons within
432 individuals at genomic sites enriched for evolutionary constraint,
and also analyzed variation within three published human genomes. We
find that high-resolution, single-site measures of evolutionary
constraint are strongly predictive of reductions in modern-day genetic
diversity across multiple annotation categories and across the allele
frequency spectrum from rare (< 1%) to high-frequency (> 10% MAF).
Furthermore, we show that putatively functional variation in an
individual genome is dominated by polymorphisms that do not change
protein sequence, and which originate from our shared ancestral
population and commonly segregate in human populations. These
observations show that common, noncoding alleles contribute
substantially to human phenotypes and that constraint-based analyses
will be of tremendous value to identify phenotypically-relevant
variants in individual genomes.

Qi Zhou, Berkeley, Doris Bachtrog Lab, "Deciphering neo-sex and B
chromosome evolution by the complete genome of Drosophila albomicans"

Abstract: We report the first Drosophila genome assembled completely
from ultrashort (45-75bp) reads. Drosophila albomicans is a unique
model for studying sex chromosome and B chromosome evolution. A pair
of its autosomes comprising 40% genome became sex-linked ~ 0.12
million years ago, creating the youngest and largest 'neo-sex' system
reported to date. It also possesses recently derived B chromosomes
that can influence fertility. We provide genome-wide evidence for
surprisingly rapid evolution on the neo-X, and for the early
degeneration of the neo-Y. In particular, we observed an excess of
tandem duplications in coding regions along the neo-Y. Finally, we
characterized non-repetitive and transcriptional sequence features of
B chromosomes. These results provide important and novel insights
into Y chromosome degeneration and the origin and function of B
chromosomes.

Hunter Fraser, Stanford, Hunter Fraser Lab, "Widespread adaptive
evolution of gene expression in budding yeast"

Abstract: Changes in gene expression have been proposed to underlie
many, or even most, adaptive differences between species. Despite the
increasing acceptance of this view, only a handful of cases of
adaptive gene expression evolution have been demonstrated. To address
this discrepancy, we introduce a simple test for lineage-specific
selection on gene expression. Applying the test to genome-wide gene
expression data from the budding yeast Saccharomyces cerevisiae, we
find that hundreds of gene expression levels have been subject to
lineage-specific selection. Comparing these findings with independent
population genetic evidence of selective sweeps suggests that this
lineage-specific selection has resulted in recent sweeps at over a
hundred genes, most of which led to increased transcript levels.
Examination of the implicated genes revealed a specific biochemical
pathway—ergosterol biosynthesis—where the expression of multiple genes
has been subject to selection for reduced levels. In sum, these
results suggest that adaptive evolution of gene expression is common
in yeast, and that regulatory adaptation can occur at the level of
entire pathways.