INSIGHTS | PERSPECTIVES

barrier that culminated in the RESEARCH CAPACITY speciation of these two crow taxa. Armed with this new very detailed genetic informa- Enabling tion, it is clear that none of the currently formulated species concepts fully apply to these the genomic two crow taxa (unless one is willing relax some stringency Sw in the various definitions). In- revolution deed, the genomes of German carrion crows are much more in Africa similar to those of hooded Po crows than to Spanish car- rion crows. Put simply, apart H3Africa is developing from the few carrion crow type capacity for health-related “speciation islands,” German Ge carrion crows could be con- genomics research in Africa sidered to represent hooded Sp crows with a black (carrion By The H3Africa Consortium* † crow) phenotype. There is a clear need for ad- ur understanding of genome biology, ditional population genomic genomics, and disease, and even hu- studies using a more dense man history, has advanced tremen- sampling, especially among dously with the completion of the 1.0 the fully black carrion crows, Human Genome Project. Technologi- on August 3, 2014 Ancestry 0.5 Sp Ge Po Sw before the complexity of repro- cal advances coupled with significant 0.0 ductive isolation and speciation Ocost reductions in genomic research have among these two taxa can be yielded novel insights into disease etiol- Speciation battleground. On either side of the narrow hybridization fully understood. The specia- ogy, diagnosis, and therapy for some of zone (dark brown), the carrion crow (Corvus corone) (dark area) tion genomics strategy already the world’s most intractable and devastat- and hooded crow (Corvus cornix) (pale area) (2 ) maintain their proved itself in unraveling the ing diseases—including ma- marked phenotypic differentiation, despite apparent lack of genetic complexities of mimicry among POLICY laria, HIV/AIDS, tuberculosis, differentiation. Genome-wide admixture analyses (inset at bottom) show many Heliconius butterfly cancer, and diabetes. Yet, de- that German carrion crows most closely resemble (80%) hooded crows, taxa ( 7) and, as in the study of spite the burden of infectious diseases and, www.sciencemag.org and are quite distinct from Spanish carrion crows. Sampling sites for Poelstra et al., stresses the im- more recently, noncommunicable diseases the present study ( 6) are shown as circles. Sp, Spain; Ge, Germany; Po, portance of using RNA-based (NCDs) in Africa, Africans have only par- Poland; Sw, Sweden. information in addition to ticipated minimally in genomics research. Of DNA. Only time will tell if, and the thousands of genome-wide association Yet, roughly a decade ago, newly pro- when, German carrion crows will adopt the studies (GWASs) that have been conducted posed DNA-based taxonomy ( 11) promised “hooded phenotype,” a fate that seems un- globally, only seven (for HIV susceptibility, to solve the species debate. A Barcode of avoidable. Until then, we can only applaud malaria, tuberculosis, and podoconiosis) Life Data Systems (BOLD) ( 12) quickly these crows for defeating Linnaeus’s curse. ■ have been conducted exclusively on Afri- Downloaded from emerged, seeking to provide a reliable, can participants; four others (for prostate cost-effective solution to the problem of REFERENCES cancer, obsessive compulsive disorder, and 1. C. Linnaeus, Systema Naturae (Tomus I, Holmiae, species identification (12 ) and a standard Impensis Laurentii Salvii, Stockholm, 1758). anthropometry) included some African screening threshold of sequence differ- 2. S. Cramp, C. M. Perrins, Eds., The Birds of the Western participants (www.genome.gov/gwastudies/). ence (10× average intraspecific difference) Palearctic (Oxford Univ. Press, Oxford, 1994), vol. 8. As discussed in 2011 (www.h3africa.org), if to speed the discovery of new animal spe- 3. E. Haring, B. Däubl, W. Pinsker, A. Kryukov, A. Gamauf, J. the dearth of genomics research involving Zoological Syst. Evol. Res. 50, 230 (2012). cies ( 13). Sometimes considered a “carica- 4. J. B. W. Wolf et al., Mol. Ecol. 19 (suppl. 1), 162 (2010). Africans persists, the potential health and ture of real taxonomy” ( 14), this approach 5. D. T. Parkin et al., Br. Birds 96, 274 (2003). economic benefits emanating from genomic failed to identify, perhaps not surprisingly, 6. J. W. Poelstra et al., Science 344, 1410 (2014). science may elude an entire continent. two American crow species and a number 7. O. Seehausen et al., Nat. Rev. Genet. 15, 176 (2014). The lack of large-scale genomics studies 8. J. L. Feder, S. P. Egan, P. Nosil, Trends Genet. 28, 342 of members of the herring gull Larus ar- (2012). in Africa is the result of many deep-seated gentatus species assemblage above the set 9. C. Darwin, On the Origin of Species by Means of Natural issues, including a shortage of African scien- threshold (13 ). Furthermore, despite past Selection (Murray, London, 1859). tists with genomic research expertise, lack 10. K. Winkler et al., Ornithol. Monogr. 63, 30 (2007). ( 3) and present (6 ) sequencing projects, 11. D. Tautz, P. Arctander, A. Minelli, R. H. Thomas, A. P. Vogler, of biomedical research infrastructure, lim- JELMER FROM POELSTRA ADAPTED , carrion crows and hooded crows can also Trends Ecol. Evol. 18, 70 (2003). ited computational expertise and resources, not be differentiated from one another 12. P. D. N. Hebert, A. Cywinska, S. L. Ball, J. R. deWaard, Proc. lack of adequate support for biomedical SCIENCE by means of DNA-barcode approaches. By R. Soc. London Ser. B 270, 313 (2003). research by African governments, and the 13. P. D. N. Hebert, M. Y. Stoeckle, T. S. Zemlak, C. M. Francis, contrast, Poelstra et al. show that much PLOS Biol. 2, e312 (2004). participation of many African scientists in more DNA sequencing data are needed, 14. O. Seberg et al., Trends Ecol. Evol. 18, 63 (2003). collaborative research at no more than the combined with RNA expression data, to level of sample collection. Overcoming these

reconstruct the evolution of a reproductive 10.1126/science.1255744 limitations will, in part, depend on African HUEY/ P. ILLUSTRATION:

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Published by AAAS scientists acquiring the expertise and facili- ties necessary to lead high-quality genom- National Institutes of Health ics research aimed at understanding health problems relevant to African populations Wellcome Trust H3Africa Research Network and to become internationally competitive in genomic science and its applications. Tunisia In June 2010, the U.S. National Institutes of Health (NIH) and UK-based Wellcome Trust, in partnership with the African Soci- Morocco ety of Human Genetics, announced a plan to enhance the ability of African scientists Egypt to apply genomic and epidemiological ap- proaches to shed light on the determinants of chronic and infectious diseases in Africa Senegal Mali Niger ( 1). The Human Heredity and Health in Af- The Gambia Sudan Nigeria rica (H3Africa) initiative, now funded at $76 Guinea million over 5 years, is focused on capacity Sierra Leone Ethiopia building, as well as specific scientific goals. H3Africa research grants are awarded di- Benin Uganda Côte d’Ivoire Ghana rectly to African institutions where principal Democratic Burkina Faso Cameroon investigators are based (table S1), which al- Republic Kenya lows African scientists to develop and direct of Congo their independent research agendas. The Tanzania NIH primary award institution program encourages formation of intra- Malawi WT primary award institution continental collaborations and development Collaborating institution of specific infrastructural elements, i.e., Zambia African-based biorepositories and a pan- African bioinformatics network (H3ABio- Other collaborating institutions are in Belgium, Canada, France, the United Net). H3Africa also includes training pro- Namibia Kingdom, and the United States Botswana Mauritius grams aimed at retaining African scientists on the continent to help build a sustainable Boundaries as depicted at Mozambique un.org/Depts/Cartographic/map/ critical mass of researchers. Open calls for profle/africa research proposals have emphasized col- South Africa laborations within Africa, plus accessible biorepositories and a bioinformatics net- work with nodes across the continent (table velopment of end-stage renal disease, that genes interact with life style (barefoot farm- S2). The footprint of H3Africa extends across is two to five times normal, respectively ( 2, ing practices) to increase susceptibility to Africa (see the map), comprising 21 grants 3). These variants also confer 29 times the podoconiosis, a neglected tropical disease in (table S1). It is anticipated that, together, risk of HIV-associated nephropathy (HIVAN) Ethiopia and Cameroon ( 9). H3Africa projects will analyze samples from ( 4). Despite these renal outcomes, the preva- A key challenge to building critical mass 50,000 to 75,000 participants. lence of the risk genotype is 13% among AA for genomic research in Africa is the reten- H3Africa is predicated on the belief that and virtually absent among those of non- tion of scientific leadership capable of devel- diseases and nonmedical issues relevant to African ancestry. The prevailing hypothesis oping and maintaining sustainable research Africans can be best explored in partnership is that APOL1 renal risk variants evolved in programs. The dearth of research-intensive with inhabitants of Africa (both researchers sub-Saharan Africa about 10,000 years ago institutions on the continent, coupled with and research participants) who can provide to confer protection against the regionally a shortage of funded positions, continues a rich context and deep knowledge of the endemic trypanosome parasite, the cause to drive Africa’s talented scientists to coun- continent’s past and present environment. of African sleeping sickness. Recent stud- tries where they have better opportunities to African genomes and the unique genetic ies led by African scientists showed that the develop their potential and pursue their in- structure of African populations harbor frequency of the risk variants, as well as the terests. Furthermore, the African continent many clues to understanding human evo- prevalence of CKD and HIVAN in carriers lacks a strong history of collaborative sci- lutionary history which, in turn, can help of the risk variant, are much higher in West entific endeavor ( 10), as African researchers shed light on disease etiology. For example, Africa (Yoruba, 28%; Igbo, 23%; the major have turned to their well-resourced counter- recent genomic studies showed that African ancestral populations of AA) where the try- parts from Europe, North America, and Asia, Americans (AA) with chronic kidney disease panosome parasite is endemic as compared rather than to their neighbors, to achieve (CKD) who harbor risk variants of the apo- with the non-endemic region of Ethiopia scientific excellence and strong publication lipoprotein L1 gene (APOL1) have a risk for (~1%) ( 5– 7). The association between CKD records. Consequently, African scientists have accelerated CKD progression and the de- and APOL1 [a component of high-density not adequately developed the necessary infra- lipoprotein (HDL) cholesterol] is shedding structure and large-scale biomedical research *H3Africa Consortium research investigators, funding light on the complicated protective rela- culture required to promote research in Af- agencies, and institutions appear in the supplementary tion between HDL cholesterol and CKD in rica. H3Africa has begun building a strong materials. †Corresponding author. Charles Rotimi, Center for global populations ( 8). In another example, foundation for genomic research based on Research on Genomics and Global Health, National Human Genome Research Institute, NIH, Bethesda, MD 20892–5635, African scientists participating in H3Africa collaboration among African scientists. Per- USA. E-mail: [email protected] have used genomic tools to understand how haps more important, H3Africa is facilitating

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Published by AAAS INSIGHTS | PERSPECTIVES the implementation of the norms and stan- dards for project oversight, goal orientation, and timely dissemination of discoveries and Measures of success for the 5-year H3Africa program training of the next generation of biomedical researchers across Africa. The consortium is Publication in high-impact journals with African lead and senior authors also addressing the use of standardized pro- Increased availability of funding for biomedical and genomics research in Africa tocols with detailed attention to community engagement and ethics approval (see below), Efective operation of a pan-African bioinformatics network protocols and policies for sharing biospeci- Regular data release mens and data, and publication policies for Establishment of one or more full-scale biorepositories large collaborative groups. Approaches to these issues are facilitated Efective release of samples within and outside of the African continent by frequent interactions among consortium Contribution to the ongoing eforts to reverse African “brain drain” members to share experiences in develop- Extension of funding for a second 5 years ing genomic research programs, to support and promote interactions among the collab- orative projects, and to jointly tackle ethical access to H3Africa data and biospecimens. and using portable devices that host data and and policy concerns. An important example To reach these not completely compatible tools and run independently of the network. is data harmonization. By standardizing ends, the H3Africa Consortium has agreed There are several criteria for success that phenotype measurement and how collected that data will be made initially available to have been defined to assess the accomplish- responses are coded to facilitate data merg- the consortium members via H3ABioNet ments of the H3Africa initiative (see the ing, statistical power for discovery of genetic until submission to the European Genome- table). Each of the component grants has a variants and for modeling gene-by-environ- phenome Archive, from which they will be set of specific, yearly milestones, progress to- ment interactions can be greatly increased. publicly accessible (through an independent ward which is assessed on an annual basis Implementation of multinational and Data and Biospecimen Access Committee). by the funders (with input from an Indepen- multiinstitutional genomics research proj- As is common in genomics, there will be a dent Experts Committee of outside scientists. ects in Africa faces additional challenges. short lag (12 months) between data submis- Both Wellcome Trust and the NIH will also Many local ethics review committees have sion and publication; this is somewhat lon- critically evaluate the progress of H3Africa little experience in genomic studies that re- ger than the norm (6 to 9 months) to provide through peer review toward the end of the quire broad consent for long-term storage resource-challenged African investigators a initial funding period. Accomplishments of and sharing of biospecimens and data, and bit more time to analyze and submit their both individual grants and the overall pro- some have balked at the concept of global manuscripts for peer review. gram will be considered in each funder deci- sharing of biospecimens and data with no Similar considerations went into de- sion process to determine whether continued immediate local benefit, viewing it as an- velopment of the policy for the release of support is justified. other form of exploitation. Several African biospecimens collected in H3Africa. The The efforts of the African scientific com- countries have restrictive legislative poli- biospecimens will be stored in an Afri- munity and their international colleagues cies that hamper sharing across national can biorepository (with backup elsewhere will not in themselves be sufficient. It is es- boundaries. Cultural beliefs and practices on the continent), and from there shared sential that national governments and re- regarding donating any body part, includ- globally for further research. Data and bio- gional political and economic organizations ing blood, need to be addressed. The grow- specimen sharing does, however, raise the support sustained funding of all research ing international debate about return of often contentious issues of ownership and fields, including genomics and research in- individual genomic results is also an issue in commercialization rights. The H3Africa frastructure development. In fact, H3Africa Africa ( 11). Finally, there are huge disparities Consortium is addressing this issue while has been useful in leveraging additional across Africa that span rural communities embracing an ethos that promotes research funding from local sources, as demonstrated adhering to long-established cultural beliefs for the global common good. Resources by support from the South African Depart- and practices on the one hand to sophisti- generated by H3Africa are expected to be ment of Science and Technology to enhance cated “citizens of the world” residing in ma- useful in future genomic research not only data collection in an H3Africa project of jor cities on the other. These communities in Africa but also globally. cardiometabolic disease genomics, an early share genetic heritage, but require different H3ABioNet has also embarked on a pro- promise of potential long-term success. ■ approaches to engagement and informed gram of training and accreditation of its bio- REFERENCES AND NOTES consent. Thus, H3Africa includes a grant informatics nodes to carry out specific data 1. Nature 465, 990 (2010). program that supports empirical research analysis techniques, i.e., of GWAS or next- 2. G. Genovese et al., Science 329, 841 (2010). on innovative approaches to informed con- generation sequencing data. Part of the train- 3. A. Parsa et al., N. Engl. J. Med. 369, 2183 (2013). 4. J. B. Kopp et al., J. Am. Soc. Nephrol. 22, 2129 (2011). sent; community engagement; and the ethi- ing involves a series of workshops, often held 5. D. M. Behar et al., Am. J. Nephrol. 34, 452 (2011). cal, legal, social, and cultural factors unique at the nodes, to prepare for an accreditation 6. I. I. Ulasi et al., Nephron Clin. Pract. 123, 123 (2013). to the African research environment. exercise. The accreditation involves giving 7. B. O. Tayo et al., Int. Urol. Nephrol. 45, 485 (2013). 8. A. R. Bentley et al., Int. J. Nephrol. 2012, 748984 (2012). The H3Africa Consortium has developed the nodes raw data sets to analyze, with their 9. F. Tekola Ayele et al., N. Engl. J. Med. 366, 1200 (2012). an approach that attempts to balance (i) pro- results being assessed by an international 10. R. De Vré et al., Closing the R&D gap in African health care. tection of the ability of African scientists to accreditation committee. One of the major McKinsey Quarterly Report (McKinsey & Co., Washington, DC, June 2010). be the first to analyze and publish findings challenges in holding training courses or 11. C. N. Rotimi, P. A. Marshall, Genome Med. 2, 20 (2010). about their main research questions, given even just joining working-group Skype calls, their limited resources and capacity to deal is poor Internet connectivity. H3ABioNet is SUPPLEMENTARY MATERIALS www.sciencemag.org/content/344/6190/1346/suppl/DC1 with data as quickly as scientists in devel- using creative approaches to overcome these oped countries with (ii) the benefit of global issues by seeking low latency alternatives 10.1126/science.1251546

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