Research topics in the Ramachandran Lab

 

Research in the lab lies in the fields of evolutionary biology and population genetics.  We use mathematical modeling, applied statistical methods, and computer simulations to make inferences about aspects of population histories from extant individuals’ genetic variation.  The lab is currently pursuing projects in the following subtopics:


Human population genetic variation and the inference of human evolutionary history


Genotypes in extant humans contain signatures of events throughout our history as a species.  We are interested in the geographic distribution of human genetic variation.  We apply and develop statistical methods to learn about how, for example, humans peopled the globe after leaving Africa, and migrated in the Americas.  Currently we are interested in the inference of local genomic ancestry for admixed individuals, as our collaboration with St. Jude Children’s Research Hospital has shown that genomic ancestry at certain loci can be a helpful prognostic for some traits related to cancer therapy outcome in children.  Currently we are studying relationships between genetic and linguistic differentiation across the globe.  [relevant articles]


The evolution and population genetics of the X chromosome


The X chromosome is a particularly interesting chromosome due to its haplo-diploid existence in human populations; males carry one X chromosome, inherited from their mothers, while females carry two X chromosomes.  Differences in patterns of genetic variation among the X and autosomes may reflect past differences between males and females in demographic parameters such as population size and migration rate; X-linked genes likely experience different levels of selection when in males compared to females.  Currently we are interested in investigating evolutionary processes that shape X-linked genetic variation across different time-depths (e.g., comparing species, as well as different human populations). 

[relevant articles]


Coalescent theory


The coalescent is a retrospective model of population genetics, and provides a mathematical framework to describe the evolutionary history of a sample of chromosomes within a population.  Currently, in collaboration with John Wakeley, we are interested in sources of variation in ancestral genetic processes and the consequences of the conceptual flaw that models of genetic ancestry typically do not take the stochasticity of Mendelian inheritance into account.  [relevant articles]

Human population genetic variation and the inference of human evolutionary history


Ramachandran, S. and Rosenberg, N. A. (2011), `A test of the influence of continental axes of orientation on patterns of human gene flow', American Journal of Physical Anthropology Vol. 146:515-529. [doi: 10.1002/ajpa.21560]


Novembre, J. and Ramachandran, S. (2011), `Perspectives on human population structure at the cusp of the sequencing era’, Annual Review of Genomics and Human Genetics Vol. 12: 245-274. (both authors contributed equally to this manuscript). [pdf]


Henn, B. M., Gignoux, C. R., Jobin, M., Granka, J. M., Macpherson, J. M., Kidd, J. M., Rodríguez-Botigué, L., Ramachandran, S., Hon, L., Brisbin, A., Lin, A. A., Underhill, P., Comas, D., Kidd, K. K., Parham, P., Norman, P. J., Bustamante, C. D., Mountain, J. L., and Feldman, M. W. (2011), `Hunter-gatherer genomic diversity suggests a southern African origin for modern humans', Proceedings of the National Academy of Sciences USA Vol. 108: 5154-5162. [free via open access at journal site]


  1. Casto, A. M., Li, J. Z., Absher, D., Myers, R., Ramachandran, S. and Feldman, M. W. (2010), `Characterization of X-linked SNP genotypic variation in globally distributed human populations', Genome Biology Vol. 11: R10.

  2. [full text at journal site] [pdf]


Ramachandran, S., Rosenberg, N. A., Feldman, M. W. and Wakeley, J. (2008), `Population differentiation and migration: coalescence times in a two-sex island model for autosomal and X-linked loci', Theoretical Population Biology Vol. 74: 291-301. [full text at journal site] [pdf]


Li. J. Z., Absher, D. M., Tang, H., Southwick, A. M., Casto, A. M., Ramachandran, S., Cann, H. M., Barsh, G. S., Feldman, M., Cavalli-Sforza, L. L. and Myers, R. M. (2008), `Worldwide human relationships inferred from genome-wide patterns of variation', Science Vol. 319: 1100-1104. [abstract at journal site]


  1. Wang, S., Lewis Jr., C. M., Jakobsson, M., Ramachandran, S., Ray, N., et al. (2007), `Genetic variation and population structure in Native Americans', Public Library of Science Genetics Vol. 3: e185. [full text at journal site]


  2. Rosenberg, N. A., Mahajan, S., Ramachandran, S., Zhao, C., Pritchard, J. K. and Feldman, M. W. (2005), `Clines, clusters, and the effect of study design on the inference of human population structure', Public Library of Science Genetics Vol. 1: e70. [full text at journal site]


Ramachandran, S., Deshpande, O., Roseman, C. C., Rosenberg, N. A., Feldman, M. W. and Cavalli-Sforza, L. L. (2005), `Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa', Proceedings of the National Academy of Sciences USA Vol. 102:  15942-15947.

[full text at journal site] [pdf]


  1. Macpherson, J. M., Ramachandran, S., Diamond, L. and Feldman, M. W. (2004), `Demographic estimates from Y-chromosome microsatellite polymorphisms:  analysis of a worldwide sample', Human Genomics Vol. 1: 345-354. [pdf]


The evolution and population genetics of the X chromosome


  1. Casto, A. M., Li, J. Z., Absher, D., Myers, R., Ramachandran, S. and Feldman, M. W. (2010), `Characterization of X-linked SNP genotypic variation in globally distributed human populations', Genome Biology Vol. 11:R10.

  2. [full text at journal site] [pdf]


Bustamante, C. D. and Ramachandran, S. (2009), `Evaluating signatures of sex-specific processes in the human genome', Nature Genetics (News and Views) Vol. 41: 8-10. (both authors contributed equally to this manuscript) [abstract at journal site] [pdf]


Ramachandran, S., Rosenberg, N. A., Feldman, M. W. and Wakeley, J. (2008), `Population differentiation and migration: coalescence times in a two-sex island model for autosomal and X-linked loci', Theoretical Population Biology Vol. 74: 291-301. [full text at journal site] [pdf]


Ramachandran, S., Rosenberg, N. A., Zhivotovsky, L. and Feldman, M. W. (2004), `Robustness of the inference of human population structure: a comparison of X-chromosomal and autosomal microsatellites', Human Genomics Vol. 1: 87-97. [pdf]


Coalescent theory


Wakeley, J., King, L., Low, B. S. and Ramachandran, S. (2012) `Gene genealogies within a fixed pedigree, and the robustness of Kingman's coalescent'.  Genetics Vol. 190:1433-1445. [pdf]


Ramachandran, S., Rosenberg, N. A., Feldman, M. W. and Wakeley, J. (2008), `Population differentiation and migration: coalescence times in a two-sex island model for autosomal and X-linked loci', Theoretical Population Biology Vol. 74: 291-301. [full text at journal site] [pdf]


Ramachandran, S., Rosenberg, N. A., Zhivotovsky, L. and Feldman, M. W. (2004), `Robustness of the inference of human population structure: a comparison of X-chromosomal and autosomal microsatellites', Human Genomics Vol. 1: 87-97. [pdf]