Gallego Romero Lab
Human Evolution + Stem Cells @ NTU
We explore the ways in which natural selection and evolutionary change have shaped the human species (and sometimes, other mammals too!). By combining the versatility of induced pluripotent stem cells with the power of functional genomics we address questions about the mechanisms of evolutionary adaptation in humans that are intractable by any other means.
Our research interests
Our lab is focused on human evolution, especially in the ways in which gene regulatory processes have contributed to it. Because gene regulation is not easily predicted (at least for now!) from sequence-level data, we use induced pluripotent stem cells (iPSCs) as models to understand the means by which multiple cellular mechanisms interact to regulate gene expression, and, under the action of natural selection, ultimately give rise to inter-species or population-level differences. We are one of few labs worldwide with an established record in generating iPSC lines from non-model organisms, and we combine this expertise with our experience working with the latest genomic technologies.
Beyond NTU, we have links to researchers at institutions like A*STAR, UC Berkeley, the Natural History Museum at the University of Copenhagen, the University of Chicago, the Wellcome Trust Sanger Institute, Penn State University, Stanford University, the Centro de Regulación Genómica in Barcelona and more.
Below you can find brief descriptions of some of our research interests.
The majority of DNA differences between humans and chimpanzee lie outside protein coding regions of the genome, strongly arguing for a large role of gene regulation as a driver of evolutionary change, especially during embryonic development. However, our understanding of the mechanisms of gene regulation is far from complete, and without access to the right tissue type, it is very difficult to predict the consequences of any mutation. Working with iPSCs gives us access to the right cell type, at the right developmental time point, from the right animal, and enables us to understand the role these differences play in giving rise to particular phenotypes.
The iPSC-driven comparative evolutionary paradigm can also be pertinent to questions about local adaptation in human groups. Of particular interest to us are populations living in the Arctic Circle, who have had to adapt to life in extreme cold conditions, as well as populations living in the Indian subcontient. Although there is well-documented evidence for adaptation in both cases, the functional mechanisms remain elusive. As above, our goal is to combine readily available allelic and sequence information with iPSCs generated from these groups and control populations in order to investigate the actual consequences of these sequence differences in living cells. However, our focus here is not the identification of developmental differences between groups, but rather the identification of population-level functional differences in terminal cell types.
Although heart disease is one of the biggest killers of both humans and captive apes, it does so through dramatically different pathways. Human cardiac failure generally stems from atherosclerotic injury leading to long-term hypoxic stress and secondary fibrotic heart damage, whereas chimpanzees and other apes accumulate fibrotic damage regardless of plaque buildup, eventually leading to cardiac failure. The mechanisms underlying this difference are unknown, but could help us understand disease progression in both humans and great apes, and potentially devise novel therapeutic approaches.
Irene Gallego Romero, PhD
Principal investigator, PhD '10 Cantab, BA Hons '06.
igr [at] ntu [dot] edu [dot] sg
I'm a human evolutionary biologist with training in genomics, biological anthropology and pluripotent stem cell biology. My research interests include understanding evolutionary adaptions at both short and long time spans - those that have occurred in specific human populations, but also those that separate us from our close evolutionary relatives. I'm also fascinated by issues surrounding the practice of science today - funding allocation, career progression and levels of inclusion and diversity of the scientific workforce.
Project officer/research technician.
psrivastava [at] ntu [dot] edu [dot] sg
Phua Zi Jin Cheryl
CPHUA002 [at] ntu [dot] edu [dot] sg
Current project: investigating interspecies differences in the oxidative stress response.
Chhabra Simarpreet Kaur
B140066 [at] ntu [dot] edu [dot] sg
Current project: functional dissection of polar bear-specific TTN mutations in cardiomyocyte function.
We are always looking for new lab members. Below are currently available opportunities, but even if they don't fit what you're looking for, get in touch if you're interested in working with us.
Funding is available for a postdoctoral reseacher to join the lab in 2016. Postdoctoral researchers will enjoy a large degree of independence and the freedom to pursue their own interests within the broad remit of the lab. Strong preference will be given to candidates already familiar with pluripotent stem cell culture and/or genomic data analysis. For more details, see this EvolDir post.
If you've read about our research and are interested in pursuing a PhD in the work we're doing, contact us. Funding is available for outstanding candidates through both NTU's School of Biological Sciences and the newly launched Lee Kong Chian School of Medicine's PhD Programme.
Undergraduate and MSc students
NTU SBS students interested in pursuing academic research during their time as students at NTU are welcome to contact Prof Gallego Romero to discuss possible projects.
C.L. Kagan*, N.E. Banovich*, B.J. Pavlovic, K. Patterson, I. Gallego Romero, J.K. Pritchard and Y. Gilad. Genetic Variation, Not Cell Type of Origin, Underlies Regulatory Differences in iPSCs. PLoS Genetics, in press. Also available at bioRxiv, doi: 10.1101/013888. * denotes equal contribution. Full text available.
I. Gallego Romero*, B.J. Pavlovic*, I. Hernando-Herraez, X. Zhou, M.C. Ward, N.E. Banovich, C.L. Kagan, J.E. Burnett, C.H. Huang, A. Mitrano, C.I. Chavarria, I.F. Ben-Nun, Y. Li, K. Sabatini, T.R. Leonardo, M. Parast, T. Marques-Bonet, L..C. Laurent, J.F. Loring, and Y. Gilad. Generation of a Panel of Induced Pluripotent Stem Cells From Chimpanzees: a Resource for Comparative Functional Genomics. eLife, doi: 10.7554/eLife.07103. Also available at bioRxiv, doi: 10.1101/008862. * denotes equal contribution. Full text available.
P.H. Sudmant, S. Mallick, B.J. Nelson, F. Hormozdiari, N. Krumm, J. Huddleston, B.P. Coe, C. Baker1, S. Nordenfelt, M. Bamshad, L.B. Jorde, O.L. Posukh, H. Sahakyan, W.S. Watkins, L. Yepiskoposyan, M.S. Abdullah, C.M. Bravi, C. Capelli, T. Hervig, J.T.S. Wee, C. Tyler-Smith, G. van Driem, I. Gallego Romero, A.R. Jha, S. Karachanak-Yankova, D. Toncheva, D. Comas, B. Henn, T. Kivisild, A. Ruiz-Linares, A. Sajantila, E. Metspalu, J. Parik, R. Villems, E.B. Starikovskaya, G. Ayodo, C. Beall, A. Di Rienzo, M. Hammer, R. Khusainova, E. Khusnutdinova, W. Klitz, C. Winkler, D. Labuda, M. Metspalu, S.A. Tishkoff, S. Dryomov, R. Sukernik, N. Patterson, D. Reich, and E.E. Eichler. Global diversity, population stratification, and selection of human copy number variation. Science, doi: 10.1126/science.aab3761. Full text available.
I. Garitaonandia*, H. Amir*, F.S. Boscolo*, G.K. Wambua, H.L. Schultheisz, K. Sabatini, R. Morey, S. Waltz, Y-C. Wang, H. Tran, T.R. Leonardo, K. Nazor, I. Slavin, C. Lynch, Y. Li, R. Coleman, I. Gallego Romero, G. Altun, D. Reynolds, S. Dalton, M. Parast, J.F. Loring** and L.C. Laurent**. Increased Risk of Genetic and Epigenetic Instability in Human Embryonic Stem Cells Associated with Specific Culture Conditions. PLOSone, doi: 10.1371/journal.pone.0118307. * and ** denote equal contributions. Full text available.
I. Gallego Romero, A. A. Pai, J. Tung and Y. Gilad. RNA-seq: Impact of RNA degradation on transcript quantification. BMC Biology, 12:42 doi:10.1186/1741-7007-12-42. Full text available.
A. Cardona, L. Pagani, T. Antão, D.J. Lawson, C.A. Eichstaedt, B. Yngvadottir, M. Than Than Shwe, J. Wee, I. Gallego Romero, S. Raj, M. Metspalu, R. Villems, E. Willerslev, C. Tyler-Smith, B.A. Malyarchuk, M.V, Derenko and T. Kivisild. Genome-wide analysis of cold adaption in indigenous Siberian populations. PLOSone, doi: 10.1371/journal.pone.0098076. Full text available.
I. Lazaridis, N. Patterson, A. Mittnik, G. Renaud, S. Mallick, P.H. Sudmant, J. Schraiber, S. Castellano, K. Kirsanow, C. Economou, R. Bollongino, K.I. Bos, S. Nordenfelt, C. de Filippo, K. Pruefer, A. Tandon, S. Sawyer, C. Posth, G. Ayodo, H.M.A. Babiker, E. Balanovska, O. Balanovsky, C. Beall, H. Ben-Ami, J. Bene, F. Berrada, F. Brighelli, G. Busby, F. Cali, C. Capelli, M. Churnosov, D.E.C. Cole, L. Damba, G. van Driem, S. Dryomov, S. Fedorova, M. Francken, I. Gallego Romero, X. Gebremedhin, M. Gubina, M. Hammer, B. Henn, U. Hodoglugil, A. Jha, R. Kittles, E. Khusnutdinova, T. Kivisild, V. Kučinskas, R. Kusainova, L. Kushniarevich, L. Laredj, S. Litvinov, T. Loukidis, R. Mahley, B. Melegh, E. Metspalu, T. Moen, J. Mountain, T. Nyambo, L. Ossipova, J. Parik, F. Platanov, O. Posukh, A. Di Rienzo, V. Romano, I. Rudan, R. Ruizbakiev, H. Sahakyan, A. Salas, M. Shriver, A. Tarekegn, D. Toncheva, S. Turdikulova, I. Uktveryte, O. Utevska, M. Voevoda, J. Wahl, P. Zalloua, L. Yeppiskoposyan, T. Zemunik, M. Thomas, S. Tishkoff, R. Villems, D. Comas, L. Singh, K. Thangaraj, R. Sukernik, M. Metspalu, M. Meyer, E.E. Eichler, J. Burger, M. Slatkin, S. Pääbo, J. Kelso, D. Reich, and J. Krause. Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature, doi: 10.1038/nature13673. Also available at bioRxiv, doi: 10.1101/001552. Full text available.
A. Bamberg Migliano, I. Gallego Romero, M. Metspalu, M. Leavesley, L. Pagani, T. Antão, D.W. Huang, B.T. Sherman, K. Siddle, C. Scholes, G. Hudjashov, E. Kaitokai, H. Mandui, A. Babalu, M. Belatti, A. Cagan, B. Hopkinshaw, C. Shaw, K. Tabbada, M. Nelis, E. Metspalu, R. Mägi, R.A. Lempicki, R. Villems, M. Mirazón Lahr and T. Kivisild. Evolution of the pygmy phenotype: evidence of positive selection from genome-wide scans in African, Asian and Melanesian pygmies. Human Biology, 85(1-3):251-84. Link.
C. Basu Mallick*, F.M. Iliescu*, M. Möls, S. Hill, R. Tamang, G. Chaubey, R. Goto, S.Y.W Ho, I. Gallego Romero, F. Crivellaro, G. Hudjashov, N. Rai, M. Metspalu, C.G.N. Mascie-Taylor, R. Pitchappan, L. Singh, M. Mirazón Lahr, K. Thangaraj, R. Villems and T. Kivisild. The Light Skin Allele of SLC24A5 in South Asians and Europeans Shares Identity by Descent . PLoS Genetics, doi: 10.1371/journal.pgen.1003912. * denotes equal contribution. Full text available.
S.M. Raj, L. Pagani, I. Gallego Romero, T. Kivisild, and W. Amos. A general linear model-based approach for inferring selection to climate. BMC Genetics doi: 10.1186/1471-2156-14-87. Full text available.
S.M. Raj, P. Halebeedu, J.S. Kadandale, M. Mirazón Lahr, I. Gallego Romero, J.R. Yadhav, M. Iliescu, N. Rai, F. Crivellaro, G. Chaubey, R. Villems, K. Thangaraj, K. Muniyappa, H.S. Chandra, and T. Kivisild. Variation at Diabetes- and Obesity-Associated Loci May Mirror Neutral Patterns of Human Population Diversity and Diabetes Prevalence in India. Annals of Human Genetics, doi: 10.1111/ahg.12028. Full text available.
I. Gallego Romero, I Ruvinsky and Y. Gilad. Comparative studies of gene expression and the evolution of gene regulation. Nature Reviews Genetics, doi: 10.1038/nrg3229. Link.
L. Pagani, T. Kivisild, A. Tarekegn, R. Ekong, C. Plaster, I. Gallego Romero, Q. Ayub, S.Q. Mehdi, M.G. Thomas, D. Luiselli, E. Bekele, N. Bradman, D.J. Balding and C. Tyler-Smith. Ethiopian Genetic Diversity reveals linguistic stratification and complex influences on the Ethiopian gene pool. American Journal of Human Genetics, doi: 10.1016/j.ajhg.2012.05.015. Full text available.
D.G. MacArthur, S. Balasubramanian, A. Frankish, N. Huang, J. Morris, K. Walter, L. Jostins, L. Habegger, J.K. Pickrell, S.B. Montgomery, C.A. Albers, Z.D. Zhang, D.F. Conrad, G. Lunter, H. Zheng, Q. Ayub, M.A. DePristo, E. Banks, M. Hu, R.E. Handsaker, J.A. Rosenfeld, M. Fromer, M. Jin, X. Jasmine Mu, E. Khurana, K. Ye, M. Kay, G.I. Saunders, M-M. Suner, T. Hunt, I.H.A. Barnes, C. Amid, D.R. Carvalho-Silva, A.H. Bignell, C. Snow, B. Yngvadottir, S. Bumpstead, D.N. Cooper, Y. Xue, I. Gallego Romero, 1000 Genomes Project Consortium, J. Wang, Y. Li, R.A. Gibbs, S.A. McCarroll, E.T. Dermitzakis, J.K. Pritchard, J.C. Barrett, J. Harrow, M.E. Hurles, M.B. Gerstein and C. Tyler-Smith. A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes. Science, doi: 10.1126/science.1215040. Full text available.
M. Hu, Q. Ayub, J.A. Guerra-Assunção, Q. Long, Z. Ning, N. Huang, I. Gallego Romero, L. Mamanova, P. Akan, X. Liu, A.J. Coffey, D.J. Turner, H. Swerdlow, J. Burton, M.A. Quail, D.F. Conrad, A.J. Enright, C. Tyler-Smith and Y. Xue. Exploration of signals of positive selection derived from genotype-based human genome scans using re-sequencing data. Human Genetics, doi: 10.1007/s00439-011-1111-9. Link.
M. Metspalu*, I. Gallego Romero*, B. Yunusbayev*, G. Chaubey, C. Basu Mallick, G. Hudjashov, M. Nelis, R. Mägi, E. Metspalu, M. Remm, R. Pitchappan, L. Singh, K. Thangaraj, R. Villems, and T. Kivisild. Shared and unique components of human population structure and genome-wide signals of positive selection in South Asia. American Journal of Human Genetics, doi: 10.1016/j.ajhg.2011.11.010. * denotes equal contribution. Full text available.
M. Rasmussen, X. Guo, Y. Wang, K.E. Lohmueller, S. Rasmussen, A. Albrechtsen, L. Skotte, S. Lindgreen, M. Metspalu, T. Jombart, T. Kivisild, W. Zhai, A. Eriksson, A. Manica, L. Orlando, F. De La Vega, S. Tridico, E. Metspalu, K. Nielsen, M.C. Avila-Arcos, J.V. Moreno-Mayar, C. Muller, J. Dortch, M.T. Gilbert, O. Lund, A. Wesolowska, M. Karmin, L.A. Weinert, B. Wang, J. Li, S. Tai, F. Xiao, T. Hanihara, G. van Driem, A.R. Jha, F.X. Ricaut, P. de Knijff, A.B. Migliano, I. Gallego Romero, K. Kristiansen, D.M. Lambert, S. Brunak, P. Forster, B. Brinkmann, O. Nehlich, M. Bunce, M. Richards, R. Gupta, C.D. Bustamante, A. Krogh, R. A. Foley, M.M. Lahr, F. Balloux, T. Sicheritz-Pontén, R. Villems, R. Nielsen, W. Jun and E. Willerslev. An Aboriginal Australian Genome Reveals Separate Human Dispersals into Asia. Science, doi: 10.1126/science.1211177. Full text available.
I. Gallego Romero, C. Basu Mallick, A Liebert, F Crivellaro, G Chaubey, A Liebert, Y Ital, R. Pitchappan, M. Metspalu, M. Eaaswarkanth, R. Villems, L. Singh, K. Thangaraj, M. G. Thomas, D. Swallow, M Mirazón Lahr, and T. Kivisild. Herders of Indian and European cattle share their predominant allele for milk tolerance. Molecular Biology and Evolution, doi: 10.1093/molbev/msr190. Full text available.
G. Chaubey, M. Metspalu, Y. Choi, R. Maagi, I. Gallego Romero, P. Soares, M. van Oven, D. M. Behar, S. Rootsi, G. Hudjashov, C. Basu Mallick, M. Karmin, M. Nelis, J. Parik, A. G. Reddy, E. Metspalu, G. van Driem, Y. Xue, C. Tyler-Smith, K. Thangaraj, L. Singh, M. Remm, M. B. Richards, M. Mirazón Lahr, M. Kayser, R. Villems, and T. Kivisild. Population genetic structure in Indian Austroasiatic speakers: The role of landscape barriers and sex-specific admixture. Molecular Biology and Evolution, doi: 10.1093/molbev/msq288, 2010. Full text available.
M. Eaaswarkhanth, I. Haque, Z. Ravesh, I. Gallego Romero, P. R. Meganathan, B. Dubey, F. A. Khan, G. Chaubey, T. Kivisild, C. Tyler-Smith, L. Singh, and K. Thangaraj. Traces of sub-Saharan and Middle Eastern lineages in Indian Muslim populations. European Journal of Human Genetics, 18(3):354-63, 2010. Full text available.
I. Gallego Romero, A. Manica, J. Goudet, L. J. Lawson-Handley, and F. Balloux. How accurate is the current picture of human genetic variation? Heredity, 102(2):120-6, 2009. Full text available.
I. Gallego Romero and C. Ober. CFTR mutations and reproductive outcomes in a population isolate. Human Genetics, 122(6):583-8, 2008. Full text available.
The lab is located in Nanyang Technological University's Yunnan Garden campus, in Singapore. We are affiliated with both the School of Biological Sciences and the Lee Kong Chian School of Medicine across the road; LKC Med itself is also affiliated with Imperial College London. Our contact details are:
Postal addressGallego Romero Lab,
60 Nanyang Drive, SBS 05n-20
Personal detailsigr [at] ntu [dot] edu [dot] sg
tel: +65 6316 2947
fax: +65 6791 3856