2014. PNAS. Adaptive, convergent origins of the pygmy phenotype in African rainforest hunter-gatherers.

Article URL
http://www.pnas.org/content/111/35/E3596.full?sid=a40e2ce9-7a55-4db4-b9ea-932241ba3942

Adaptive, convergent origins of the pygmy phenotype in African rainforest hunter-gatherers

1. George H. Perrya,1,2, 
2. Matthieu Follb,c,1, 
3. Jean-Christophe Grenierd, 
4. Etienne Patine,f, 
5. Yohann Nédélecd,g,
6. Alain Pacisd,g, 
7. Maxime Barakatth, 
8. Simon Graveli, 
9. Xiang Zhouj, 
10. Sam L. Nsobyak, 
11. Laurent Excoffierc,l,
12. Lluis Quintana-Murcie,f, 
13. Nathaniel J. Dominym, and 
14. Luis B. Barreirod,n,1,2

Author Affiliations

1. aDepartments of Anthropology and Biology, Pennsylvania State University, University Park, PA 16802;
2. bSchool of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland;
3. cSwiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;
4. dSainte-Justine Hospital Research Centre, Montreal, QC, Canada H3T 1C5;
5. eInstitut Pasteur, Unit of Human Evolutionary Genetics, 75015 Paris, France;
6. fCentre National de la Recherche Scientifique, URA3012, 75015 Paris, France;
7. gDepartment of Biochemistry, Faculty of Medicine, University of Montreal, Montreal, QC, Canada H3T 1C5;
8. hSchool of Computer Science, and
9. iDepartment of Human Genetics, McGill University, Montreal, QC, Canada H3A 1B1;
10. jDepartments of Statistics and Human Genetics, University of Chicago, Chicago, IL 60637;
11. kDepartment of Pathology, Makerere University, Kampala, Uganda;
12. lInstitute of Ecology and Evolution, University of Bern, 3012 Bern, Switzerland;
13. mDepartments of Anthropology and Biological Sciences, Dartmouth College, Hanover, NH 03755; and
14. nDepartment of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, QC, Canada H3T 1C5

The evolutionary history of the human pygmy phenotype (small body size), a characteristic of African and Southeast Asian rainforest hunter-gatherers, is largely unknown. Here we use a genome-wide admixture mapping analysis to identify 16 genomic regions that are significantly associated with the pygmy phenotype in the Batwa, a rainforest hunter-gatherer population from Uganda (east central Africa). The identified genomic regions have multiple attributes that provide supporting evidence of genuine association with the pygmy phenotype, including enrichments for SNPs previously associated with stature variation in Europeans and for genes with growth hormone receptor and regulation functions. To test adaptive evolutionary hypotheses, we computed the haplotype-based integrated haplotype score (iHS) statistic and the level of population differentiation (FST) between the Batwa and their agricultural neighbors, the Bakiga, for each genomic SNP. Both |iHS| and FST values were significantly higher for SNPs within the Batwa pygmy phenotype-associated regions than the remainder of the genome, a signature of polygenic adaptation. In contrast, when we expanded our analysis to include Baka rainforest hunter-gatherers from Cameroon and Gabon (west central Africa) and Nzebi and Nzime neighboring agriculturalists, we did not observe elevated |iHS| or FST values in these genomic regions. Together, these results suggest adaptive and at least partially convergent origins of the pygmy phenotype even within Africa, supporting the hypothesis that small body size confers a selective advantage for tropical rainforest hunter-gatherers but raising questions about the antiquity of this behavior.

열대우림에 살아온 부족 몇 몇이 피그미 형질(작은 몸집)을 가지게 된 진화적 배경에 대한 기존의 가설에서 Adaptive evolution이라는 부분도 테스트하고 Convergent evolution이라는 부분도 테스트한다.

데이터 자체는 genome wide SNP data이다.

피그미 population과 비교를 위해 Control로 인근 지역에 사는 농경 population에서도 SNP을 typing했다.

분석 툴은 ADMIXTURE로 population structure와 individual별 ancestry proportion을 구했고

HAPMIX로 SNP별 ancestry proportion을 구했다.

Genomic region을 나누어 각 region별로   키 vs proportion of 농경population's ancestry 를  구하여

피그미 형질과 연관된 genomic region을 뽑아냈다.

피그미 형질과 연관된 것으로 뽑아낸 genomic region에서 signature of selection을 scan하였다.

이것이 피그미 형질에 대한 population 수준에서의 genome-wide association 연구이지만 

다른 어떤 중요한 형질에 대해서도 population 수준에서 특이점이 있을 때 (예를 들어 멕시코인이 술을 잘 마신다)   비슷한 방법으로 술 잘 마시는 것과 연관된 genomic region을 찾고,  술 잘 마시는 형질이 adaptive evolution인지 테스트할 수 있을 것이다.

마찬가지로 러시아 인도 술을 잘 마시고 멕시코 인도 술을 잘 마시는데 그것이 convergent evolution인지 테스트할 때에도 비슷한 데이터 디자인과 분석 툴을 사용하면 될 것이다.