Wen-Ya Ko, Ph.D. Postdoctoral Fellow Department of Genetics School of Medicine University of Pennsylvania 426 Clinical Research Building 415 Curie Boulevard Philadelphia, PA 19104-6145 215-746-2315

Research Interests Education Awards Professional Experience Conference Presentations Publications Academic Service Professional Affiliations Service to Biology Department

Research Interests

My primary interest is to study evolutionary dynamics of genetic variation and the underlying mechanisms in natural populations.  I am broadly interested in studying a variety of topics including theoretical and statistical population genetics, genome evolution, conservation genetics, host-parasite co-evolution, and genetic basis of phenotypic adaptation or deficiency (e.g., genetic diseases in humans).

Human population genomics

Disease susceptibility may arise as a consequence of adaptation to other environmental stress. Recent findings have suggested that higher rates of kidney disease in African Americans may be attributed to several risk alleles at the APOL1 gene. These risk alleles may have provided resistance to trypanosoma infection (African sleeping sickness) in the ancestors of African Americans. I am currently studying nucleotide variation of the APOL1 gene from diverse African populations and discovered several haplotypes that cause amino acid changes at the functional domains required to lyse trypanosoma parasites in human serum. I have conducted a genomic approach to identify signatures of recent selection on these haplotypes and found that different alleles may be favored by selection in different human populations. This pattern of spatially heterogeneity in selection toward alternative alleles may be relevant to the distinct distributions of two trypanosoma subspecies or the possibility of the deleterious effects of these haplotypes in kidney function.                 

My research also focused on identification of genetic variants relevant to susceptibility of infectious diseases in human populations.  I studied genetic variation of glycophorin A and B, two major erythrocyte-surface receptors that interact with the malaria-causing parasites, Plasmodium falciparum, across diverse human ethnic groups in Africa and obtained several novel and exciting findings.  We identified signatures of balancing and positive selection on different extracellular domains of glycophorin A. We also showed that MN blood-type polymorphisms encoded by glycophorin A have been maintained jointly by balancing selection and gene conversion in many malaria-endemic populations in Africa. In addition, we identified a haplotype causing three amino acid changes in the extracellular domain of glycophorin B.

Figure 1 Geographic distribution of malaria endemicity and sampled populations in Africa. The map of spatial limits and endemic levels of malaria in Africa is kindly provided by Drs. Robert W. Snow and Carlos Guerra from the Malaria Atlas Project (www.map.ox.ac.uk) published in Snow et al. (2005). The value in parentheses indicates Tajima’s D statistics for exon 2 of GYPA.

Figure 2. Three dimensional model of glycophorins A (GYPA) and B (GYPB). (A) Extracellular domain of GYPA. O- and N-glycosylated amino acid residues are labeled in magenta and green, respectively. Amino acid residues where polymorphic (poly) or fixed (fix) changes occurred are colored in red. (B) Three dimensional structure of the transmembrane domain of GYPA (PDB code: 1AFO). The two fixed mutations occur at the extracellular peptide residues (in red) adjacent to the helical region. (C) Extracellular domain of GYPB. Amino acid residues that are both glycosylated (O-link) and variable are colored in pink. The MN and Ss blood groups are determined by amino acid variants at GYPA and GYPB, respectively. The M and N antigens are determined by two genetically linked amino acid variants of GYPA where M blood type is determined by Ser and Gly at position 1 and 5, respectively, and N blood type is determined by Leu and Glu (introduced by gene conversion from GYPB) at these two sites. The S and s are determined by Met and Thr, respectively, at position 29 of the polypeptide chain of GYPB.

Molecular evolution and phylogeny in Drosophila

Before joining Sarah’s lab, my doctoral studies with Dr. Hiroshi Akashi at Penn State University focused on molecular phylogeny and evolution of Drosophila melanogaster and its closely related species (D. simulans, teissieri, yakuba, erecta, and orena).  Although the phylogeny among these species was thought well established, we found strong molecular evidence supporting an alternative tree topology (Ko et al. 2003). We also studied patterns and rates of molecular evolution among these lineages and the underlying evolutionary forces. We inferred nucleotide changes on the tree branches among these species and found prevalence of non-stationary nucleotide evolution and weak selection at synonymous sites (Akashi et al. 2006). We also identified striking regional heterogeneity in patterns and rates of base composition evolution in D. yakuba and orena (Ko et al. 2006). These results illustrate that temporal (on a gene tree) and spatial (near telemetric chromosomal regions) fluctuations in evolution parameters may be frequent even among closely related species, and imply that stationarity assumptions in modeling DNA evolution for phylogenetic reconstruction or in detecting footprints of natural selection (e.g., dN/dS test) may be often violated.

Figure 3: A maximum likelihood tree of species in the Drosophila melanogaster group inferred from a concatenated sequence of Adh + Adhr + Gld + ry genes (7164 bp).  Bootstrap values (1000 replicates) on each node are shown and represent, from top to bottom: Maximum likelihood (ML), neighbor-joining distance (NJ), and maximum parsimony (MP) values. “ * ” indicates identical bootstrap values for ML, NJ, and MP (see Ko, David, and Akashi 2003).

Education

Awards

Burroughs Wellcome Travel Scholarship for Ecology and Evolution of Infectious Diseases (EEID) Meeting
Atlantic City, New Jersey March 22-25, 2010

Postdoctoral Research Travel Award for the Society of Molecular Biology and Evolution (SMBE)
Lyon, France, July 4 - 8 2010  (top 20 list)

Trainee Research Award for the American Society of Human Genetics (ASHG)
Washington DC, USA, November 2 - 6 2010  (semifinalist)

Platform Moderator for the session of Evolutionary and Population Genetics in the American Society of Human Genetics (ASHG)
Washington DC, USA, November 2 - 6 2010

Biology Graduate Student Research Excellence Awards
Pennsylvania State University, 2006

Professional Experience:

Postdoctoral Researcher, Department of Genetics, University of Pennsylvania School of Medicine

Research Associate, Department of Biology, University of Maryland

Teaching Assistant, Department of Biology, Pennsylvania State University

• Population Genetics, in 2003, 2005, and 2006 (lectured by Dr. Hiroshi Akashi)
• Molecular Evolution, in 2002 and 2005 (lectured by Dr. Stephen Schaeffer and by Dr. Kateryna Makova, respectively)
• Genetics, in 2002 (lectured by Drs. Stephen Schaeffer and Mitch Price)
• Biology of Molecules and Cell, in 2006 (lectured by Dr. Graham Thomas)

Research Assistant, Section of Integrative Biology, University of Texas at Austin, July 1999 - May 2000

• Molecular phylogeny of fireflies in North America (worked with Dr. Kathrin Stanger-Hall at Dr. David Hillis's Lab)

Research Assistant, Department of Biology, Tunghai University, Taiwan, January - June 1999

• Species investigation of bats in Taiwan
• Dynamics of species compositions of small mammals in Ta-Ta-Jia,Yu- Shan National Park, Taiwan

Research Assistant, Molecular Oncology Laboratory, Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, 1997 - 1998

• Apoptosis in neuroblastoma cells induced by hydrogen peroxide

Research Assistant, Wildlife Ecology Laboratory, Forestry Department, National Pintung University of Science and Technology, 1993 - 1995

• Species diversity survey of Ruei-Jan stream Nature Reserve, Nantou County, Taiwan
• Species diversity survey after forest fire in Ta-Ta-Jia, Yu-Shan National Park, Taiwan
• Assessment of survival and rehabilitation of Formosa Flying Fox, Pteropus dasymallus formosus, Green Island, Taiwan

Conference Presentations

Ko, W.-Y. and S.A. Tishkoff, Effects of gene conversion and natural selection on the evolution of human glycophorins coding for MNS polymorphism in malaria endemic African populations. Young Researchers Conference On Evolutionary Genomics, Tokyo, Japan, August 1-2 2011 Invited talk

Ko, W.-Y., F. Gomez, and S.A. Tishkoff, Spatially heterogeneous selection on human ApoL1 variants among diverse African populations in trypanosomiasis endemic areas. The annual meeting of the Society for Molecular Biology and Evolution (SMBE), Kyoto, Japan, July 26 - 30, 2011  Platform presentation

Ko, W.-Y., K. Kaercher, and S.A. Tishkoff (2010) Adaptive evolution of human glycophorin loci in malaria endemic African populations. The 60th annual meeting of the American Society of Human Genetics (ASHG), Washington DC, Nov 2 - 6, 2010 Platform presentation with trainee research award (selected as the featured research in a press briefing session at the Meeting on the latest advances in evolutionary and population genetics research)

Ko, W.-Y., K. Kaercher, and S.A. Tishkoff (2010) Adaptive evolution of human glycophorin loci in malaria endemic African populations. The annual meeting of the Society for Molecular Biology and Evolution (SMBE), Lyon, France, July 4 - 8 2010 Platform presentation with travel award

Ko, W.-Y., F. Gomez, and S.A. Tishkoff, An evolutionary and population genetic approach to malaria susceptibility in Africa. The 79^th Annual Meeting of the American Association of Physical Anthropologists (AAPA), Albuquerque, New Mexico, Apr 14 - 17, 2010 Invited talk

Ko, W.-Y., K. Kaercher, and S.A. Tishkoff, Population genetic analysis of erythrocyte surface glycoproteins in malaria-endemic human populations of Africa. 

Poster presentations:

58^th Annual meeting of the American Society of Human Genetics, Philadelphia, Pennsylvania, Nov 11 - 15, 2008

Ecology and Evolution of Infectious Disease PI Meeting, Albuquerque, New Mexico, Dec 02 - 05, 2007

Ko, W.-Y., K. Kaercher, and S.A. Tishkoff (2007) Population genetic analysis of erythrocyte surface glycoproteins in malaria-endemic human populations of Africa. Ecology and Evolution of Infectious Disease PI Meeting, Albuquerque, New Mexico, Dec 02 - 05, 2007. Poster presentation

Ko, W.-Y., S. Piao, and H. Akashi, Strong regional heterogeneity in base composition evolution on the Drosophila X chromosome.

Poster presentations:

Evolution 2006, the join annual meeting of the Society for the Study of Evolution (SSE), the Society of Systematic Biologists (SSB), and the American Society of Naturalists (ASN) at Stony Brook University, Stony Brook, NY, June 23 - 27 2006

Genomes, Evolution, and Bioinformatics, the annual meeting for the Society for Molecular Biology and Evolution at Arizona State University, Tempe, AZ, May 24 - 28 2006

47th Annual Drosophila Research Conference, Houston, TX, March 29 - April 2 2006

The Comparative and Functional Genomics of Summer Symposium at Pennsylvania State University, University Park, PA, July 20 - 23 2005

Oral presentations:

Northeast Ecology and Evolution Conference (NEEC) at Pennsylvania State University, University Park, PA, March 18 - 20 2005

Ko, W.-Y., R. David, J. Anoop, C.-F. Lin, S. Piao, and H. Akashi (2004) Lineage-specific molecular evolution in the Drosophila melanogaster species subgroup. Genome and Evolution conference for the Society for Molecular Biology and Evolution at Pennsylvania State University, University Park, PA, June 17 - 20 2004. Poster presentation

Ko, W.-Y., R. David, and H. Akashi, Molecular phylogeny of the Drosophila melanogaster species subgroup. 

Poster presentations:

Eastern Great Lake Molecular Evolution Meeting (EGLME VIII) at Cornell University, Ithaca, NY, April 24 2004

The Annual Conference for the Society of Molecular Biology and Evolution (SMBE), Newport Beach, CA, June 26 - 29 2003

Publications

Ko, W.-Y., F. Gomez, and S.A. Tishkoff (2012) Spatially heterogeneous selection on human ApoL1 variants among diverse African populations in trypanosomiasis endemic areas (In preparation for submission)

Gomez, F., W.-Y. Ko, and S.A. Tishkoff (2012) An evolutionary and population genetic approach to malaria susceptibility in Africa. (An invited review article in an edited volume for the conference of the American Association of Physical Anthropologists (AAPA), scheduled to be in press in 2012)

Ko, W.-Y., and S.A. Tishkoff, Disease and Evolution. Evolution of human erythrocyte-specific genes involved in malaria susceptibility, In "Evolution In The Fast Lane: Rapidly Evolving Genes and Genetic Systems". Singh R.S., Xu J. and Kulathinal R. J. Ed. Oxford University Press, Oxford. (Scheduled to be in press in 2012)

Ko, W.-Y., K. Kaercher, E. Giombini et al. 2011 Effects of gene conversion and natural selection on the evolution of human glycophorins coding for MNS polymorphism in malaria endemic African populations. Am J Hum Genet 88: 741-754 (Selected as the featured article)

Ko, W.-Y., S. Piao, and H. Akashi (2008) With- and between-species sequence variation in Drosophila teissieri and Drosophila yakuba: evolutionary mechanisms of Codon Bias and protein Evolution. (in preparation for submission to Genetics)

Iida, K., D. L. Cox-Foster, X. Yang, W.-Y. Ko, D. R. Cavener (2007) Expansion and evolution of insect GMC oxidoreductases. BMC Evolutionary Biology 7:75

Ko, W.-Y.,  S. Piao, and H. Akashi (2006) Strong regional heterogeneity in base composition evolution on the Drosophila X chromosome. Genetics 174:349-362

Akashi, H., W.-Y. Ko, S. Piao, A. John, P. Goel, C. F. Lin, and A. Vitins (2006) Molecular evolution in the Drosophila melanogaster species subgroup: Frequent parameter fluctuations on the time-scale  of molecular divergence. Genetics 172:1711-1726

Ko, W.-Y., R. David, and H. Akashi (2003) Molecular phylogeny of the Drosophila melanogaster species subgroup.  J. Mol. Evol. 57:562-573

Ko, W.-Y., A note on the playing-dead Behavior of Pipistrellus abramus. Notes of Wildlifers and Newsletter of Wildlifers 4(2):10 (in Chinese)

Ko, W.-Y. (1995) Reproductive cycle of the house bat, Pipistrellus abramus, in South Taiwan. A Tunghai University Publication (Master's thesis, in English).

Academic Service:

Moderator:

• 60^th Annual Meeting of the American Society of Human Genetics (ASHG) for the session of Evolutionary and Population Genetics, Washington DC, USA, November 2 - 6, 2010

Manuscripts reviewed:

• BMC Evolutionary Biology (with Dr. H. Akashi)
• BMC Source Code for Biology and Medicine
• GENE
• Journal of Molecular Evolution (with Dr. H. Akashi)
• Molecular Biology and Evolution
• PLoS genetics

Professional Affiliations:

• Genetics Society of America
• American Society of Human Genetics
• Society for Molecular Biology and Evolution
• Society for the Study of Evolution

Service To Biology Department:

Graduate Affairs Committee of Biology Department, Pennsylvania State University, 2006