Our lab analyzes molecular genetic variation in order to reconstruct the evolutionary history and relationships of human populations and human pathogens.  Specifically, we are interested in 1) biocultural evolution of populations in the Horn of Africa and the Arabian peninsula, 2) processes of colonization and migration as revealed in East Asia and the New World, 3) identification of genetic variants involved in complex diseases using alcohol dependence as a model system, and 4) use of ancient DNA to reconstruct past genetic diversity and evolutionary 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.  For disease studies, we focus on candidate genes and for ancient DNA studies, we assay high copy number genes or genomes, such as mitochondrial DNA. We study populations from around the world with an emphasis on Horn of Africa/Arabian, New World, and East Asian groups.  Some of the current projects in the lab include:

Colonization and migration

1) Biocultural evolution of populations in the Horn of Africa and the Arabian peninsula. Genetic variation in populations located throughout the Horn of Africa and the Arabian peninsula is analyzed in order to test hypotheses concerning migrations across the Red Sea and the evolution of language families and food production methods.  This region of the world is known to be important for the emergence of anatomically modern humans, but it 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 Ethiopia, Eritrea, Oman and Yemen.  Additional countries will be included as the project develops.  Postdoctoral fellow Ryan Raaum and graduate student Amy Non are beginning analyses of mitochondrial and nuclear markers of Semitic-speaking populations.  Graduate student Drew Kitchen is also conducting a phylogenetic analysis (maximum parsimony and maximum likelihood) of lexical characters from Semitic languages in order to directly compare genetic and linguistic data.  Collaboration with Steve Brandt (University of Florida), Peter Schmidt (University of Florida) and Juris Zarins (Southwest Missouri State University).  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".

2) 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.  Questions of interest include the original settlement of East Asia and its influence on colonization of neighboring regions. 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.  Larissa Tarskaia (visiting professor from Yakutsk, Siberia) collected over 2000 Siberian  DNA samples and began an analysis of mitochondrial variation in these populations.  Graduate student Rebecca Gray has completed a study on the unusually high level of variation we detected at the mitochondrial 9bp locus in the Sakha of Siberia.  Collaboration with Khishge Sambuughin (NINDS, NIH), Lev Goldfarb (NINDS, NIH), Ke Xu (NIAAA, NIH), Ma Cui (Guangzhou Psychiatric Hospital, China), Jeff Long (University of Michigan), David Goldman (NIAAA, NIH), Rick Kittles (Howard University), and Anne Stone (Arizona State University).

Disease

3) 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.

Ancient DNA

5) 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.

6) 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).

7) 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.