ANT 3930 (0832) HONORS MOLECULAR GENETICS AND EVOLUTION

Prof. Connie J. Mulligan

Class meets in 117 Little

Class time: Tuesday, periods 3-5, with a 15 min break

Contact information:

Prof. Connie Mulligan

B119 Turlington Hall

(352)392-2253, ext 248

mulligan@anthro.ufl.edu

http://www.clas.ufl.edu/users/mulligan/Webpage/index.html

Office hours: Mon and Thurs, 10:30-12:00

Course summary: ANT 3930 will examine the use of molecular genetic data to investigate the evolution and history of humans. The completion of the human genome sequence has greatly facilitated the application of molecular genetic data to questions of human prehistory. Specifically, variant sites in the human genome sites can now be identified through a computer search rather than spending weeks or months in the laboratory. These variant sites can then be used in a number of investigations, such as the reconstruction of past migration events or the detection of admixture or gene flow in a population. Specific topics to be discussed include the emergence of anatomically modern humans in Africa (out-of-Africa vs. multiregionalism theories), Neanderthal genetics (did we interbreed?), colonization of Europe, and the use of ancient DNA to study human evolution.

Reading and course format: Two textbooks (The Seven Daughters of Eve by Brian Sykes and Genetics and the Search for Modern Human Origins by John Relethford) will be used to present the fundamentals of molecular genetics and how these data are applied to anthropological questions. Relevant journal articles will be used to highlight the major contributions in the field of molecular anthropology. A course packet of journal articles and related material is available at Custom Copies (309 NW 13th St, across from Krispy Kreme Donuts, 352-375-2707). The course meets once a week for three hours and the course format is lecture plus discussion with substantial class participation. Evaluation of student performance is based on class participation, weekly quizzes, problem sets, an oral presentation, and an exam. Although basic molecular biology concepts will be reviewed, some knowledge of DNA structure, Mendelian genetics, and molecular biology is expected. Additional information is provided by several websites:

http://www.clas.ufl.edu/users/mulligan/Webpage/3930.2004/3930home.html – website for class

http://www.uflib.ufl.edu/ej/ - UF database of available electronic journals (may only be available from a campus computer)

http://www.ncbi.nlm.nih.gov/PubMed - National Library of Medicine database of over 11 million journal articles dating back to the 1960s

http://www.genome.gov/glossary.cfm – NIH-maintained glossary of genetic terms

http://www.genomesonline.org/ - status of genome sequencing projects

http://www.genome.gov/LegislativeDatabase - Database of federal and state laws focused on genetic issues, such as genetic testing and counseling, insurance and employee discrimination, etc.

http://www.gene.ucl.ac.uk/hugo/ - Human Genome Organisation

http://www.stanford.edu/group/morrinst/hgdp.html – Human Genome Diversity Project (dated, good for historical perspective)

Grading: Final grades will be determined by the following five categories, each of which contributes 100 points to the final grade: participation (100 pts), 10 quizzes or set of questions/comments (10 pts each), 4 homework exercises (25 pts each), oral presentation (100 pts), exam (100 pts). Possible points total 500. Grades will be based on the following point percentages: 90-100%=A, 87-89%=B+, 80-86%=B, 77-79%=C+, 70-76%=C, 67-69%=D+, 60-66%=D, < 59%=E.

- Participation in class discussions is required of all students and will be based on each student’s contribution of original discussion, comments, questions, etc. to the class.

- Each class, either a quiz will be given or students will hand in at least three original comments or questions based on the reading material. Quizzes will cover the day’s reading material and will be closed-book. The lowest grade (of quizzes or comments/questions) will be dropped. Missed quizzes or comment/questions cannot be made up.

- There will be four homework exercises involving the analysis of hypothetical or actual molecular data. The exercises are intended to give students an opportunity to perform data analyses similar to those conducted in the discussion papers and will be graded on effort and accuracy. Exercises must be turned in two weeks after they are assigned. Students who miss the class in which an exercise is assigned are expected to turn the exercise in on time, i.e. two weeks after the missed class.

- Each student will present a 15-20 min oral presentation of one journal article that will be chosen by the student from articles in the course packet. The presentation must use MS PowerPoint. All students will read all articles being presented and be prepared to participate in discussions of the articles.

- The exam will consist of problems similar to the homework exercises and essay questions. Questions must be answered during the exam period without reference to books or notes of any kind. Calculators may be used, but no palm pilots or similar devices will be allowed. Make-up exams will be scheduled only in extenuating circumstances and will require a doctor’s note, police report, or similar supporting documentation.

Class attendance policy: Because the class meets only one time per week and because the class format is mainly discussion, it is very difficult to make up missed classes by borrowing notes, etc. Therefore, students are required to attend all classes. Computers are allowed in class for taking notes, but are not allowed during exams. Class discussions/lectures cannot be recorded in any manner without special permission.

Accommodations for students with disabilities: If you require accommodation due to a disability, please make an appointment during my office hours so that we may discuss your needs. Students requesting classroom accommodation must first register with the Dean of Students Office. The Dean of Students Office will provide documentation to the student who must then provide this documentation to the Instructor when requesting accommodation.

Academic honesty: As a result of completing the registration form at the University of Florida, every student has signed the following statement: “I understand that the University of Florida expects its students to be honest in all their academic work. I agree to adhere to this commitment to academic honesty and understand that my failure to comply with this commitment may result in disciplinary action up to and including expulsion from the University.” An excellent website that discusses plagiarism (provides a definition and many useful examples) is http://www.csubak.edu/ssric/Modules/Other/plagiarism.htm. All students should read this material at least once.

UF Counseling Services: On-campus services are available for students having personal problems or lacking clear career and academic goals. They include:

University Counseling Center, 301 Peabody Hall, 392-1575, personal and career counseling
Student Mental Health, Student Health Care Center, 392-1171, personal counseling
Sexual Assault Recovery Services (SARS), Student Health Care Center, 392-1161, sexual assault counseling
Career Resource Center, Reitz Union, 392-1601, career development assistance and counseling

Course schedule:

August 24 – Introduction

Video – The Gene Hunters (example of studies conducted under the Human Genome Diversity Program)

August 31 – Lecture - Background on DNA structure, human genetics, molecular anthropology

Reading assignment - Seven Daughters of Eve (SDE) – Chapters 2, 3, 4 – DNA, blood group analysis to genes, mitochondrial DNA

Course packet:

1) The recent African genesis of humans, Wilson and Cann, April, 1992, Scientific American, 68-73

Exercise #1 – Restriction site mapping and investigation

September 7 – Lecture – How to read a scientific journal article, sample PubMed search, colonization of the New World

Skim Genetics and the Search for Modern Human Origins (MHO) – Chapter 1

Course packet:

1) Extensive mitochondrial diversity within a single Amerindian tribe, Ward et al., 1991, Proc Natl Acad Sci USA, 88:8720-8724

2) Population genetics, history, and health patterns in Native Americans, Mulligan et al., 2004, Annu Rev Genomics Hum Genet, 5:295-315

Questions on Exercise #1

September 14 – Lecture – Sample oral presentation, molecular genetic identification of Russian Tsar, colonization of Polynesia

Reading assignment - SDE – Chapters 5, 6, 7 – case study of the Russian Tsar and molecular analysis of Pacific Island populations

Course packet:

1) Identification of the remains of the Romanov family by DNA analysis, Gill et al., 1994, Nature Genetics, 6:130-135

2) Press release AND Molecular, forensic and haplotypic inconsistencies regarding the identity of the Ekaterinburg remains, Knight et al., 2004, Ann Hum Bio, 31:129-138

Exercise #1 due

September 21 – Lecture – colonization of Europe, replacement by modern humans or interbreeding with Neanderthals?

Reading assignment - SDE – Chapters 8, 9 – colonization of Europe and Neanderthals

Course packet:

1) DNA sequence of the mitochondrial hypervariable region II from the Neandertal type specimen, Krings et al., 1999, Proc Natl Acad Sci USA, vol 96, pp 5581-5585

2) The Neandertal type site revisited: Interdisciplinary investigations of skeletal remains from the Neander Valley, Germany, Schmitz et al., Proc Natl Acad Sci USA, 99:13342-1347

Exercise #2 assigned

September 28 – Lecture – hunter-gatherers/pastoralism, minimum spanning networks, recombination

Reading assignment - SDE – Chapters 10,11 – controversies surrounding theories on first Europeans

Course packet:

1) Genetics and the population history of Europe, Barbujani and Bertorelle, 2001, Proc Natl Acad Sci USA, 98:22-25

2) Genetic evidence for different male and female roles during cultural transitions in the British Isles, Wilson et al., 2001, Proc Natl Acad Sci USA, 98:5078-5083

October 5 - Lecture – analysis of Y chromosome genetic variants, comparison with mtDNA results

Reading assignment - SDE – Chapter 13 – Adam Joins the Party

Course packet:

1) Press release AND The genetic legacy of Paleolithic Homo sapiens sapiens in extant Europeans: A Y chromosome perspective, Semino et al., 2000, Science, 290:1155-1159

2) Y chromosomes traveling south: The Cohen modal haplotype and the origins of the Lemba – the “Black Jews of the Southern Africa”, Thomas et al., 2000, Am J Hum Genet, 66:674-686

3) Founding mothers of Jewish communities: Geographically separated Jewish groups were independently founded by very few female ancestors

Exercise #2 due

October 12 - Lecture – ads and disads of ancient DNA

Reading assignment - SDE – Chapters 1, 12, 14 – ancient DNA

Reading assignment - SDE – Chapters 15-23 (just for fun, not quiz or exam) – fictional accounts of original European founding women

1) DNA sequence from Cretaceous period bone fragments, Woodward et al., 1994, Science, 266:1229-1232 AND Comments by Hedges and Schweitzer, Henikoff, Allard et al., Zischler et al., and Woodward, 1995, Science, 268:1191-1194

2) Analysis of ancient DNA from a prehistoric Amerindian cemetery, Stone and Stoneking, 1999, Phil Trans R Soc Lond B, 354;153-159

Exercise #3 assigned

October 19 - Lecture – Genetic drift, similarities/differences of mt, Y, and autosomal DNA, primate phylogeny

Reading assignment - Genetics and the Search for Modern Human Origins (MHO) – Chapters 1, 2 – molecular analysis of human evolution

1) Y genetic data support the Neolithic demic diffusion model, Chikhi et al., 2002, Proc Natl Acad Sci USA, 99:11008-11013

2) Implications of natural selection in shaping 99.4% nonsynonymous DNA identity between humans and chimpanzees: Enlarging genus Homo, Wildman et al., 2003, Proc Natl Acad Sci USA, 100:7181-7188

October 26 - Lecture – Evolution of genus Homo, replacement and multiregional theories of human origins

Reading assignment - MHO – Chapter 3 – The Modern Human Origins Debate

1) Genetic and fossil evidence for the origin of modern humans, Stringer and Andrews, 1988, Science, 239:1263-1268

2) Press release AND Evidence for a genetic discontinuity between Neandertals and 24,000-year-old anatomically modern Europeans, Caramelli et al., 2003, Proc Natl Acad Sci USA,

Exercise #3 due

November 2 - Lecture – Origin and timing of our most recent common ancestor

Reading assignment - MHO – Chapter 4 – In Search of our Common Ancestor

1) Press releases AND X chromosome evidence for ancient human histories, Harris and Hey, 1999, Proc Natl Acad Sci USA, 96:3320-3324.

2) Press release AND Comments AND Mitochondrial DNA sequences in ancient Australians: Implications for modern human origins, Adcock et al., 2001, Proc Natl Acad Sci USA, 98:537-542

Exercise #4 assigned

November 9 - Lecture – Patterning of genetic diversity

Reading assignment - MHO – Chapters 5, 6 – measurement and geographic distribution of genetic diversity, genetic distances

1) Press release AND Comments AND Global patterns of linkage disequilibrium at the CD4 locus and modern human origins, Tishkoff et al., 1996, Science, 271:1380-1387

2) Alu insertion polymorphisms and human evolution: Evidence for a larger population size in Africa, Stoneking et al., 1997, Genome Res, 7:1061-1071

November 16 – Lecture – population size, population history

Reading assignment - MHO – Chapter 7 – How Many Ancestors?

1) Genetic evidence for larger African population size during recent human evolution, Relethford and Jorde, 1999, Am J Phys Anthropol, 108:251-260

2) Genetic traces of ancient demography, Harpending et al., 1998, Proc Natl Acad Sci USA, 95:1961-9167

Exercise #4 due

November 23 – Lecture –Neanderthal genetic diversity, relationship to modern humans

Reading assignment - MHO – Chapters 8, 9 – Neanderthal DNA

1) A reanalysis of the ancient mitochondrial DNA sequences recovered from Neandertal bones, Gutierrez et al., 2002, Mol Biol Evol, 19:1359-1366

2) Absence of regional affinities of Neandertal DNA with living humans does not reject multiregional evolution, Relethford, 2001, Am J Phys Anthropol, 115:95-98

November 30 - Lecture – Human disease - evolution of AIDS, evolution of malaria and malaria resistance

Review for exam

Course packet:

1) The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe, Libert et al., 1998, Hum Mol Gen, 7:399-406

2) Chromosome-wide SNPs reveal an ancient origin for Plasmodium falciparum, Mu et al., 2002, Nature, 418:323-326

3) Haplotype diversity and linkage disequilibrium at human G6PD: Recent origin of alleles that confer malarial resistance, Tishkoff et al., 2001, Science, 293:455-462

December 7 - Exam