Ongoing research projects in the Mulligan laboratory

Our lab studies human evolution in terms of population history as well as human adaptation. 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 origin 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 focus on candidate genes as well as genomic variation. 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 Puerto Rico for disease studies. Current projects in the lab include:


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 students Amy Non and Aida Miro and former postdoctoral fellow Ryan Raaum are conducting analyses of mitochondrial and nuclear markers of populations from these geographic regions. Former graduate student Drew Kitchen has 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 is 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 Khishge Sambuughin (Uniformed Services University of the Health Sciences).

Human disease

Genetic and sociocultural risk factors for hypertension in African-Americans. Genetic (candidate genes and ancestry informative markers), biological (stress biomarkers), and sociocultural (measures of race, SES, etc) data are analyzed in order to simultaneously test for the contribution of genetic and environmental factors to risk of hypertension. Different methods to measure 'race' are specifically included in order to investigate ideas of identity and implications for human health. 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").

Ancient DNA

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 will conduct the faunal analyses, Albano Beja-Pereira (Portugal) will do genetic analyses of modern animals and Mulligan lab postdoctoral fellow Birgitta Kimura is conducting the ancient DNA analyses in our lab.
 


Former projects

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.

Evolution of treponemal syndromes.  DNA from modern treponemal strains (three human sub-species, rabbit and simian species) is assayed for variation in genes in the tpr (Treponema pallidum repeat) gene family.  These data have relevance for evolution of the gene family as well as evolution of the treponemes. Graduate student Becca Gray has conducted phylogenetic analyses on a sequence dataset from our U Washington collaborators.  We find evidence for multiple gene conversion events within the studied tpr genes. Our results are generally consistent with a relatively coincident evolution of the human sub-species Treponema pallidum subsp. pallidum (venereal syphilis), subsp. pertenue (yaws), and subsp. endemicum (endemic syphilis or bejel). Collaboration with Sheila Lukehart (U of Washington) and Arturo Centurion-Lara (U of Washington).

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.