We are a mathematical, theoretical, and computational lab in genetics
and evolution. Research in the lab addresses problems in evolutionary
biology and human genetics through a combination of mathematical
modeling, computer simulations, development of statistical methods, and
inference from population-genetic data.
4-22-2016 Several projects from the lab have been in
4-5-2016 We congratulate PhD
student Amy Goldberg
on the publication of
her Nature article
entitled "Post-invasion demography of prehistoric humans in South
America." In this work, Amy and her colleagues use the locations and
dates of South American archaeological sites to estimate the time
trajectory of the human population size history of the
continent. Read the news
Edge, and Jaehee Kim report that forensic genetic
markers selected for their use in individual identification possess
a surprising level of information about genetic ancestry. Moreover, their
study finds that a general correlation holds for genetic
markers between their information about individual identity and
ancestry information. The result makes use of theory from the lab on the
connection between measures of genetic diversity and genetic
1-5-2016 The lab helps celebrate the centennial of the
student Amy Goldberg
develops a model for sex-biased admixture on the X-chromosome, a
curious mathematical sequence leads to an unexpected connection deep
in the Genetics archive.
Read about the oscillatory functions and
coupled recursions encountered in this scholarly adventure with a
surprise appearance of the Fibonacci numbers.
10-7-2015 PhD student Jonathan Kang has
analyzed a new approach for prioritizing individuals for whole-genome
sequencing. This approach, based on minimizing a quantity
the average distance to the closest leaf, seeks to identify a
set of samples that will provide optimal templates for imputing
genotypes in additional individuals. He compares the method to an
earlier algorithm, also from the lab: maximizing phylogenetic
Jonathan's article has been selected
for Genetics issue
9-30-2015 Postdoc Filippo Disanto reports a
study of the
number of coalescent histories for gene trees and species trees in
the lodgepole family. He uses connections with other
combinatorial structures from theoretical computer science to derive
exact results in the context of a new problem arising from
biology. The term "lodgepole" for the tree shape he considers is based
on a resemblance to the pattern in which lodgepole pine needles branch
off the main twig. The work follows earlier studies from the lab on
coalescent histories (,
9-24-2015 We report
an article on detecting
selective sweeps using a new statistic, the haplotype allele frequency
(HAF) score. This statistic tabulates the frequencies of alleles on a
haplotype, and it has distinctive patterns of change during a selective
sweep. The approach is related to previous articles from the lab that
examined haplotype properties for detecting a deviation from null
population-genetic models (
The lab reports two articles in this month's issue of Genetics.
note reporting the
software CLUMPAK is now
available. What does the program do? It clumps and packages results from
Structure and related programs. What does it produce? A pack of
Distruct plots a
clumpak! CLUMPAK is reported by PhD
graduate Naama Kopelman. Former
Jakobsson contributed to the
student Doc Edge uses a
mathematical model to interpret the implications of two computations
in population genetics---the partition of genetic variance, and the
genetic assignment of individual ancestry---for human phenoypic
differentiation. He concludes that a typical selectively neutral
quantitative phenotype is comparable to a single genetic locus in
terms of its ancestry information.
The study is part of a
special issue of Studies in History and Philosophy of Biological
and Biomedical Sciences on Genomics and Philosophy of Race.
a study of the
effect of sex-biased admixture on the X chromosome. The study has a
number of surprises: (1) The admixture level on the X chromosome is not
simply a 2/3-and-1/3 linear combination of female and male
parameters. (2) A difference in X chromosomal and autosomal levels of
admixture need not imply male bias entering the admixed population from
one source and female bias from a second source: the bias can be in the
same direction in both source populations, but with different
magnitudes. (3) A third surprise involves the appearance of a sequence
related to the Fibonacci numbers! The paper follows two previous
articles from the lab on mechanistic models of admixture
- We report a review
of three cases in which differences in levels of genetic diversity
across populations contribute to population differences in societal
variables related to forensic testing, transplantation matching,
and genome-wide association. The study also considers a fourth scenario,
performing a reanalysis that contests a claim that within-population
genetic diversity has influenced global economic
development. PhD student Jonathan Kang contributed to the project.
to Genomes blog post from the Genetics Society of America]
5-22-2015 We congratulate three lab members who have
recently been awarded competitive fellowships!
5-15-2015 PhD student Nandita Garud
from Dmitri Petrov's lab next
door reports on the
mathematical properties of statistics used in detecting soft selective
sweeps. Nandita provides an improvement to the use of proposed
and H2/H1, applying the
modified statistics to analyze selection in Drosophila. The work relies on
the lab's mathematical analysis of homozygosity and the frequency of
the most frequent allele
We are pleased to congratulate the lab's Administrative Associate Elena
Yujuico on receiving the Humanities & Sciences Dean's Award
of Merit! This award recognizes staff members who make outstanding
contributions in the School of Humanities & Sciences.
- Nicolas Alcala Swiss National Science Foundation Early
Postdoc.Mobility Fellowship (2015-2017).
- Amy Goldberg Achievement Rewards for College Scientists Fellowship from
the Northern California Chapter of the ARCS Foundation (2015-2016).
- Lawrence Uricchio Stanford Center for Computational,
Evolutionary, and Human Genomics Postdoctoral Fellowship (2015-2016).
story in the Stanford Medicine SCOPE blog discusses with
Noah the journal Theoretical Population Biology, for which he
serves as the Editor-in-Chief.
new study by Nicole
Creanza et al. performs the largest joint analysis of genetic
variation and phonemic variation in populations worldwide. The study
uncovers a number of new coevolutionary patterns in genes and languages,
including correspondences in spatial axes of genetic and linguistic diversity,
and a difference for genes and languages in the effects of population
Pemberton contributed to the project.
commentary by Keith Hunley]
12-10-2014 Filippo Disanto reports a
about anomalous ranked gene trees (ARGTs), demonstrating that as the
number of species increases, the fraction of ranked species trees that
produces ARGTs approaches 1. The work extends earlier existence
results on ARGTs
12-3-2014 Approximate Bayesian Computation (ABC)
provides a way of performing statistical inference from complex
models that can be simulated but for which likelihoods are difficult
to evaluate. Former postdoc Erkan
Buzbas reports a new advance in ABC techniques for scenarios
in which even simulating from the model is challenging
Approximate Approximate Bayesian Computation. Read
about it here!
Goldberg reports a surprising result, that properties of admixture
obtained from autosomal loci alone can be informative about sex bias in the
history of admixture. The result is obtained in a
new article in the
November 2014 issue of Genetics. It builds on an
studied by former postdoc Paul Verdu, who is also a contributor
to the project.
10-1-2014 Nicolas Alcala joins us as a new
postdoc. Nicolas completed his PhD in ecology and evolution at the
University of Lausanne, performing several studies in the
population-genetic modeling of demography and population structure. We
are pleased to welcome Nicolas to the group!
student Doc Edge reports
a new paper on the mathematical properties of population-genetic
statistic FST. Doc has refined the bounds
on FST as functions of the frequency of the most
frequent allele and homozygosity obtained in an
earlier study from the
lab, considering a finitely-many-alleles case instead of the less
constrained infinitely-many-alleles case. The work extends the lab's
line of work on mathematical properties
of population-genetic statistics.
8-28-2014 We welcome Ilana Arbisser as a PhD
student in the lab. Ilana completed her BA at the University of
Pennsylvania, where she majored in biology with a concentration in
biological mathematics. Ilana rotated through the lab during the
spring quarter, working on problems in coalescent theory. Welcome Ilana!
new study in PLoS
Genetics led by former postdoc Paul Verdu reports on
admixture in Native American and First Nation populations of the
Pacific Northwest. The study describes recent European admixture in
coastal and inland populations from British Columbia and Alaska, also
uncovering evidence of recent East Asian admixture in the inland
groups. It is the first genomic investigation focused on the Pacific
Northwest region. Former
Pemberton was a contributor to the project.
8-8-2014 We congratulate PhD student Ethan Jewett on
the defense of his thesis, "Models, tools, and approaches for studying
genetic and cultural variation." Ethan's thesis examines a series of
problems on coalescent lineage distributions, with applications to the
study of population growth and migration, inference of species trees, and
genotype imputation. He also conducts analyses of variation in word usage,
both in the United States and in Cape Verde, posing questions about
cultural evolution. Ethan's work has been recognized with the Department
of Biology's Samuel Karlin Prize in Mathematical Biology. Congratulations
Former postdoc Trevor
a study of
population-genetic factors that affect worldwide variation in the
inbreeding coefficent, showing that the value of this popular
population-genetic statistic increases with increased consanguinty
but also with measures that reflect decreasing genetic diversity
and increasing genetic isolation. The study is part of a special issue
of Human Heredity on Consanguinity and Genomics.
6-25-2014 We congratulate co-mentored graduate student
Dr. Naama Kopelman, on the completion of her PhD! Naama's thesis,
conducted at Tel Aviv University on "The complex genealogy of Jewish
populations," examines the genetic relationships of Jewish
populations using both microsatellite loci
 and genome-wide single
nucleotide polymorphisms . She also
performs a theoretical investigation of the effect of admixture on
tree-reconstruction algorithms, inspired by the placement of
Jewish populations in a neighbor-joining tree
. Naama has begun a
postdoc with Itay Mayrose, Department of Molecular Biology and
Ecology of Plants, Tel Aviv University.
6-22-2014 A new special issue of Human
Biology focuses on the genetics of Jewish populations. The lab
contributes to two research studies in the special issue:
new paper by former postdoc
determines the mean of the deep coalescence cost, measuring the fit of a
gene tree to a species tree, under probability distributions for the
shapes of gene trees and species trees. This paper extends Cuong's
previous analysis focusing on the maximum deep coalescence cost rather
than the mean . The
work advances knowledge of an important concept in estimation of species
3-29-2014 Former graduate
DeGiorgio has compared the properties of several different
methods for species tree inference, using sequence data from eight
species of North American
pines. The paper
support theoretical work from the lab on properties of the deep coalescence cost
 and extend the lab's work on
trees and species trees.
- In a study of
Y-chromosomal lineages in the Samaritans, Oefner et al. find
that most Samaritans have a distinctive Y chromosome similar to that
of Jewish Cohen lineages. Curiously, among the Samaritans, the only
exception distant from the Cohen model haplotype is that of the
Samaritan Cohen lineage.
- An international team including graduate student Naama Kopelman
studies genetic relationships with the Ashkenazi Jewish population in a
large genome-wide data
set, finding considerable
shared ancestry with other Jewish populations and tracing more distant
relationships to other populations of Europe and the Middle East.
to the special issue, by Noah
Rosenberg and Steven Weitzman.
3-14-2014 Graduate student Ethan Jewett has
summarized and enhanced results on the properties of the number of
lineages in genealogies obtained under the coalescent model. His work
produces new approximations that can facilitate uses of the coalescent
in large samples and complex demographies. The
article appears in
the May 2014 issue of
Theoretical Population Biology.
2-5-2014 A new
paper in the IEEE/ACM
Transactions on Computational Biology and Bioinformatics describes
the properties of coalescent histories for gene trees and species trees
that resemble the "caterpillar" shape. The work extends earlier projects
from the lab on coalescent histories
, and it advances the lab's
research program on the
combinatorics of evolutionary trees.
1-2-2014 Former graduate
DeGiorgio has started a lab as Assistant Professor of Biology at
Pennsylvania State University. We wish him all the best in his new position!
describes a unifying principle that underlies the production
of anomalous gene trees (AGTs), gene trees that are more probable
under an evolutionary model than the gene tree that matches the species
tree. The new principle, identifying pairs of consecutive short branches
as key to AGT production, refines earlier work from the lab on AGTs
11-18-2013 We welcome postdoc Filippo Disanto!
Filippo joins us from the University of Cologne, where he completed an
earlier postdoctoral fellowship in population genetics and bioinformatics.
11-8-2013 A report
by Doc Edge et
al. appears online
in Evolution, Medicine, and Public Health, on surprises that
occur in the application of population-genetic principles to
association mapping. The article describes windfalls arising from
population geneticsand pitfalls.
Past news items
SELECTED RECENT PUBLICATIONS
A Goldberg, P Verdu, NA Rosenberg (2014) Autosomal
levels are informative about sex bias in admixed populations.
Genetics 198: 1209-1229.
M DeGiorgio, J Syring, AJ Eckert, AI Liston, R Cronn, DB
Neale, NA Rosenberg (2014) An empirical evaluation of two-stage
species tree inference strategies using a multilocus dataset from North
American pines. BMC Evolutionary Biology 14: 67.
File 1 (.xlsx, accession numbers)]
File 2 (.pdf, supplementary analyses)]
File 3 (.zip, data)]
M Jakobsson, MD Edge, NA Rosenberg (2013) The
relationship between FST and the frequency of the
most frequent allele.
Genetics 193: 515-528.
JH Degnan, NA Rosenberg, T Stadler (2012) A
of the set of species trees that produce anomalous ranked gene trees.
IEEE/ACM Transactions on Computational Biology and Bioinformatics
TJ Pemberton, D Absher, MW Feldman, RM Myers, NA
Rosenberg, JZ Li (2012) Genomic patterns of homozygosity in worldwide
human populations. American Journal of Human Genetics 91:
Table 2 (.zip)]
Table 3 (.zip)]
Table 4 (.zip)]
Table 5 (.zip)]
S Ramachandran, NA Rosenberg (2011) A test of the influence
of continental axes of orientation on patterns of human gene flow.
American Journal of Physical Anthropology 146: 515-529.
ZA Szpiech, NA Rosenberg (2011) On the size
distribution of private microsatellite alleles. Theoretical
Population Biology 80: 100-113.
NA Rosenberg, L Huang*, EM Jewett*, ZA
Szpiech*, I Jankovic*, M Boehnke (2010) Genome-wide
association studies in diverse populations. Nature Reviews
Genetics 11: 356-366. [Abstract]
JT Mosher, TJ Pemberton, K Harter, C Wang,
EO Buzbas, P Dvorak, C Simon, SJ Morrison, NA Rosenberg
(2010) Lack of population diversity in commonly used human embryonic
stem-cell lines. New England Journal of Medicine 362: 183-185.
NM Kopelman, L Stone, C Wang, D Gefel, MW Feldman, J
Hillel, NA Rosenberg (2009) Genomic microsatellites identify
shared Jewish ancestry intermediate between Middle Eastern and
European populations. BMC Genetics 10: 80. [Abstract] [Full text at
journal website] [PDF]
M DeGiorgio, M Jakobsson, NA Rosenberg (2009)
Explaining worldwide patterns of human genetic variation using a
coalescent-based serial founder model of migration outward from
Africa. Proceedings of the National Academy of Sciences USA
M Jakobsson*, SW Scholz*, P Scheet*, JR Gibbs, JM
VanLiere, H-C Fung, ZA Szpiech, JH Degnan, K Wang, R
Guerreiro, JM Bras, JC Schymick, DG Hernandez, BJ Traynor, J
Simon-Sanchez, M Matarin, A Britton, J van de Leemput, I Rafferty, M
Bucan, HM Cann, JA Hardy, NA Rosenberg, AB Singleton (2008)
Genotype, haplotype and copy-number variation in worldwide human
populations. Nature 451: 998-1003. [Abstract] [PDF] [Supplement]