Our lab studies human evolution in terms of population history as well as human disease. We analyze human genomic variation that is neutral (in order to reconstruct human population history) and variation that is subject to natural selection (to study the complex causes and spread of human disease and human pathogens). For the study of population history, we assay genetic variants in the mitochondrial genome, the sex chromosomes, and the autosomes in order to provide the most complete and accurate representation of human evolution. We also use ancient DNA to reconstruct human population history. For disease studies, we take a biocultural perspective for a better understanding of complex diseases. We investigate both candidate genes as well as genomic variation and we also study changes in methylation for a better understanding of epigenetic variation and changes in gene expression. We study populations from around the world with an emphasis on the Arabian Peninsula, Horn of Africa, New World, and East Asia for population history studies and the continental US and the Democratic Republic of Congo for disease studies. Current projects in the lab include:
Human disease
Association of epigenetic alterations, maternal prenatal stress exposure,and birth outcomes among new mothers and newborns in the Democratic Republic of Congo. This project is one of the first to test the possibility that extreme environmental or psychosocial stressors may result in altered health outcomes, possibly in a heritable, multigenerational manner. Changes in methylation profiles from mothers and their newborns are tested for association with maternal stress exposures and newborn birth outcomes. Next-generation sequencing methods and methylation microarrays are used to generate the methylation data. Extended interviews and surveys with mothers are used to develop culturally relevant measures of stress. We are also collecting observational behavioral data on mother-newborn interactions and measuring cortisol as a biological indicator of stress exposure. We are working with women in the Democratic Republic of Congo, where ongoing civil war and the use of rape as a weapon has created one of the most stressful and traumatic environments for women on the planet. Graduate student Nikki D'Errico (University of Florida) has worked in the DRC for many years and is in charge of all data and sample collection and analysis of the socio-cultural data. Collaborators also include Lance Gravlee and Alyson Young (UF Anthropology) and Darlene Kertes (UF Psychology). This work is supported by NSF grant, entitled "Epigenetic alterations and stress among new mothers and neonates in the Democratic Republic of Congo: A biocultural investigation of the intergenerational effects of war".
Genetic and sociocultural risk factors for hypertension in African-Americans. Genetic (candidate genes and ancestry informative markers), epigenetic (genome-wide and candidate gene promoters), biological (stress biomarkers), and sociocultural (measures of race, discrimination, SES, etc) data are analyzed in order to simultaneously test for the contribution of genetic and environmental factors to risk of hypertension. Epigenetic modifications are thought to mediate between the environment and genome and may modify expression of the genome in response to particular events in an individual's life. Discrimination is studied as a potential stressor with particular significance in the African-American community to investigate possible causes of racial disparities in hypertension, specifically, and health, more generally. Close collaboration with the African-American community in Tallahassee, FL (http://healthequity.us/) is a key component of the study. Graduate student Tamar Carter is analyzing both genetic and sociocultural data in order to more fully understand how to study complex diseases with racial disparities. Collaboration with Lance Gravlee (University of Florida). This work is supported by NSF grant BCS-0820687, entitled "Genetic ancestry, race and health disparities: A biocultural approach".
Human population history
Biocultural
evolution of populations in the Arabian Peninsula and the Horn of
Africa. Genetic variation in
populations located throughout the Arabian Peninsula and the Horn of
Africa is analyzed in order to test hypotheses concerning
migrations
across the Red Sea and the evolution of language families. This region
of the world is known to be important for
the emergence of anatomically modern humans, but is also important
for more recent evolution. Specifically, we are interested in
determining the origin and directionality of migrations across the Red
Sea and the evolution of the Semitic language family. Mitochondrial,
X and Y, and autosomal genes and variants are assayed in order to
address these questions. Specific regions of interest include
Yemen, Ethiopia, and Eritrea. Graduate student Aida Miro is
analyzing both simulated and empirical data to better understand the
demographic parameters of dispersals out of Africa. Graduate student
Deven Vyas is generating whole mitochondrial genome sequences in order
to date the oldest lineages in Yemen. Former graduate student Amy Non
and former postdoctoral fellow Ryan
Raaum conducted analyses of mitochondrial and nuclear markers of
populations
from these geographic regions. Former graduate student Drew Kitchen
completed a
phylogenetic analysis of
lexical characters from Semitic languages in order to directly compare
genetic and linguistic data. Collaboration with Chris Ehret (UCLA),
Steve Brandt
(University of Florida), and Peter
Schmidt (University of Florida). This work was supported by NSF grant
BCS-0518530, entitled "Human dispersals out of Africa: Mitochondrial
and Y chromosomal genetic analysis of Eritrean and Omani populations".
Colonization of East Asia and the New World. Genetic variation in Asian and New World indigenous populations is analyzed in order to reconstruct original colonization events and subsequent migrations. The number, timing and genetic make-up of colonizing migration(s) to the New World is of particular interest. Mitochondrial, X and Y, and autosomal genes and variants are assayed in order to provide the most complete and accurate representation of these events. Specific populations and regions of interest include Mongolia, Siberia, and China in Asia and Panama and US Native American populations in the Americas. Former graduate student Drew Kitchen completed a Bayesian skyline plot analysis that incorporated archaeological, paleoclimatic and historical data to formulate a three-stage theory of peopling of the Americas. Collaboration with Michael Miyamoto (UF Biology) and Khishge Sambuughin (Uniformed Services University of the Health Sciences).
Former projects
Domestication of the donkey in Africa. Mitochondrial D-loop and cytb sequence is being generated from wild ass and donkey specimens collected from museums around the world. Questions include the origin and timing of donkey domestication in Africa. This is a collaboration with Fiona Marshall (Washington University, St. Louis), who is PI of a NSF grant entitled “Domestication of the donkey: Aridity, mobility and the development of African pastoral societies”. Marshall conducted the faunal analyses, Albano Beja-Pereira (Portugal) conducted the genetic analyses of modern animals and Mulligan lab postdoctoral fellow Birgitta Kimura conducted the ancient DNA analyses in our lab.
Genotype:phenotype
associations in alcoholism and related
disorders. Genetic variants that are associated with
alcohol dependence and related disorders or effects such as binging,
flushing, or antisocial personality disorder are being
investigated. Questions of interest include the use of recent
methods to detect variants with small effect on the disease, the
relationship between the presumed protective effect of flushing and
prevalence of alcohol dependence, and application of methods to fetal
alcohol syndrome. Assayed variants occur in alcohol metabolism
genes (ADH, ALDH) and neurological response genes
(alpha-synuclein). Native Americans suffer a
disproportionately high rate of alcohol dependence relative to other
U.S. populations and several populations have agreed to participate in
our study. Genetic typing and analysis is complete for two
American Indian populations (Southwest and Plains). Graduate
student Becca Gray
and Lindsey Williams
(University Scholars fellow/undergraduate student) have recently
assayed
variants in alpha-synuclein, a gene that is involved in Parkinson's
disease in humans and was recently implicated in alcohol consumption in
a rat model. Collaboration with Jeff Long (University of
Michigan), David Goldman (NIAAA, NIH), Andrew Singleton (NIA, NIH) and
Rongling Wu (University of
Florida). This work was supported by NIH grant R03 AA12906.
Genetic
variation
and domestication of bovids in Africa. Mitochondrial D-loop sequence is
generated using bovid material from Eritrea. Skeletal material
derives from two sites: Adi Nefas (900 YBP) and Sembel (2800-2400
YBP). Questions include domestication of cattle in Africa and
presence of other bovids at early times in Africa. Marina Ascunce
is conducting molecular analyses and Drew Kitchen is performing
phylogenetic and statistical analyses. Collaboration with Peter
Schmidt (University of Florida), Fiona Marshall (Washington
University, St. Louis) and Richard Meadow (Harvard University).
Origin of
treponemal syndromes. Treponemal DNA from skeletal
material in Danish cemeteries dating to 1500 A.D. is being
analyzed. Questions of interest include the evolution of venereal
syphilis and the other treponemal syndromes. Variants that
distinguish the various treponemes are assayed from ancient and
contemporary material in order to elucidate evolution of the treponemes
and their associated syndromes. Sherin Smallwood (University
Scholars Program undergraduate student) is extracting DNA and
performing
test PCR amplifications. Collaboration with Mark Shriver
(Anthropology, Penn State), Noreen Tuross (Harvard University), Sheila
Lukehart (U of Washington), and Arturo Centurion-Lara (U of
Washington). See #4 (above) for treponemal study using modern strains.