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ILRI/Camille Hanotte
The mosaic genome of African cattle: a unique adaptive
genetic resource
Olivier Hanotte & Sumaya Kambal
TropAg2022 – HarlanIV
31st Oct – 2nd Nov 2022
Brisbane - Australia
© ILRI/Camille Hanotte
CIMMYT
Mexico City
Mexico
IFPRI
Wash. DC
USA
CIP
Lima
Peru
CIAT
Cali
Colombia
Bioversity
International
Rome Italy
AfricaRice
Cotonou
Benin
IITA
Ibadan
Nigeria
ILRI
Nairobi
Kenya
Addis
Ababa,
Ethiopia
ICARDA
Beirut
Lebanon IWMI
Colombo
Sri Lanka
IRRI
Los Banos
Phillippines
WorldFish
Penang
Malaysia
International Livestock Research Institute (ILRI)
One of the 12 One CGIAR research centres
ILRI is a CGIAR
research centre, a
global research
partnership for a food-
secure future. CGIAR
science is dedicated to
reducing poverty,
enhancing food and
nutrition security, and
improving natural
resources and
ecosystem services.
3
Livestock Genetics – ILRI cattle, chicken, small ruminants
The right genetics for the right
environment
Understanding
& meeting
farmer needs
Climate is a key determinant of
constraints – feed, disease, heat
stress……
Adaptation
Improved resilience, productivity,
profitability, human nutrition
Performance
Reduced environmental impact,
including reduced GHG intensity
Mitigation
Purpose: Within-breed selection of cattle adapted to predicted changes in the
environment by studying the sensitivity of milk production to environmental
conditions (feeding level and temperature humidity).
2009
But what about between breeds …..
© Dan Bradley
Kuri cattle, Lake Chad
Cattle distribution (Felius 1995) African main agro-ecologies (HarvestChoice/IFPRI 2010)
• There are at least 150 recognized indigenous
African cattle ‘breeds’, a fifth of world’s cattle
breeds; 300 million heads (Rege and Bester 1998;
Dessie and Okeyo, 2019)
Bos taurus
~8000 ya
~4000 ya
Bos indicus
~1500 ya
Ethiopian Boran
White Fulani
Fogera Tuli
Nganda
Red Fulani Mursi
N’Dama
Kenya Boran
https://www.ilri.org/publications/story-cattle-africa-why-diversity-matters
African Indigenous
Cattle: Unique
Genetic Resources
in a Rapidly
Changing World
O. Mwai , O.
Hanotte, Y-J Kwon,
S. Cho (2015) Asian
Asian - Autralasian
Journal of Animal
Sciences
Example of African cattle adaptation …….
Etc……
North – African sites with early presence of African cattle
https://twitter.com/Physiologos/status/1564712371884621824/photo/1
© Jean-Loic Le Quellec (2022)
X
2000
Science 2002
Bradley et al. PNAS 1996
Bofiglio et al. PloSOne 2012
Science 2002
D loop mtDNA
15 microsatellite loci
One Y micro
Dave Elsworth
Köppen-Geiger
Climate
Classification
Full genome
high coverage
sequencing of
SNPs diversity
OWSD – ILRI
PhD fellow
Sumaya
Kambal
Breed Abbrev. #IND Country
Abergelle ABR 11 Ethiopia
Afar AFR 9 Ethiopia
Arado ARD 11 Ethiopia
Arsi ARS 10 Ethiopia
Bagaria BAG 10 Ethiopia
Bale BAL 10 Ethiopia
Begait BEG 20 Ethiopia
ET-Boran EBO 40 Ethiopia
Choke CHK 9 Ethiopia
Erob ERB 8 Ethiopia
Fogera FOG 9 Ethiopia
Goffa GOF 9 Ethiopia
Horro HOR 11 Ethiopia
Mursi MUR 10 Ethiopia
Ogaden OGD 9 Ethiopia
Raya RAY 11 Ethiopia
Semien SEM 10 Ethiopia
KE-Boran KBO 16 Kenya
Centre and West African zebu
(CAZ)
Breed Abbrev. #IND Country
Aryashai ARY 10 Sudan
Butana BUT 36 Sudan
Gash GAS 8 Sudan
Kenana KEN 30 Sudan
Baggara BAG 19 Sudan
Fulani FUL 10 Sudan
Toupouri TOP 15 Chad
Gudali GUD 1 Cameroon
Red Fulani RFL 1 Cameroon
White Fulani WFL 1 Cameroon
Zebu Gobra ZGB 12 Senegal
Zebu Maure ZMR 7 Senegal
East African zebu (EAZ)
537
Samples
Breed Abbrev. #IND Country
Ghana Shorthorn GSH 10 Ghana
Kapsiki KAP 1 Cameroon
Namchi NAM 1 Cameroon
Baoule BAO 16 Burkina Faso
S-Muturu SMT 10 Nigeria
F-Muturu FMT 13 Nigeria
N’Dama GND 13 Gambia
N’Dama NND 17 Nigeria
N’Dama SND 12 Senegal
N’Dama UND 21 Guinea
African taurine (AFT)
Breed Abbrev. #IND Country
Gourounsi GOR 10 Burkina Faso
Kuri KUR 10 Chad
Sheko SHK 9 Ethiopia
Djakkore DJK 11 Senegal
Ankole ANK 10 Uganda
African admixed (AAD)
45
Populations
Köppen-Geiger Climate
Classification
MAF and LD pruned data
2,994,996 SNPs
• MAF < 0.05
• r2 > 0.5
PC1 vs PC2 PC1 vs PC3
PC1: 62.7%
PC2: 6.74%
PC3: 5.86%
PC1: 62.7%
Population Admixture – K = 4
Zebu ancestries
decreased as we
move from East to
the West
Small shared Muturu and
N’Dama taurine ancestry
background
(shorthorn/longhorn) within
zebu (EAZ and CAZ)
Treemix
results
PC2 (6.74%) separate CAZ from EAZ
Centre and West African zebu
(CAZ)
East African zebu (EAZ)
African taurine (AFT)
PC3 (5.86%) separate longhorn taurine
(N’dama) from shorthorn taurine (Muturu)
CAZ EAZ
Shorthorn
Longhorn
Fst: 0.196 between Savanna
Muturu and Forest Muturu
Fst: 0.227 between
Savannah Muturu
and N’Dama Guinea
PC2: 6.74%
PC3: 5.86%
• Low genetic differentiation (Fst <= 0.01) within almost all
EAZ and CAZ populations
• Moderate genetic differentiation (Fst = 0.02 to
0.04) between EAZ and CAZ populations
Entry points of the Zebu ancestral population on the African
continent – Red Sea port Adulis (?)
The Horn of Africa
Adulis (Eritrea)
R = - 0.88
R2 = 0.78
R = - 0.82
R2 = 0.67
Eastern Sahara (Nabta Playa)
R = 0.68 R2 = 0.46
2010
‘’ I have often speculated on the probable cause through
which each separate district in Great Britain came to
possess in former times its own peculiar breed of
cattle…..’’
‘’… I conclude that, although slight differences in the
nature of the climate, food, etc., as well as changed habits
of life, aided by correlation of growth, and the occasional
appearance from unknown causes of considerable
deviations of structure, have all probably played their
parts; yet the occasional preservation in each district of
those individual animals which were more valued by each
owner has perhaps been even more effective in the
production of the several British breeds…’’
1868
2017
The genome landscape of indigenous African cattle
J. Kim, O. Hanotte et al. (2017) Genome Biology
Kim, Hanotte et al. Genome Biology 2017
PRL - Senepol
PRLR - Senepol
PRLH – African Zebu
2020
2020
Admixture
characterization
Admixture
dating
Signature of selection
adaptation
Signature of selection
ancestry
Candidate ancestral selected
gene identification
Identification of unique
African ancestry candidates
Whole-genome sequence analysis of 45 cattle breeds (16 indigenous African population, 172 animals), 35 billion reads or
3.5 terabytes of sequences
Whole-genome sequence analysis of 45 cattle breeds (16 indigenous African populations), 16 indigenous, 35 billion reads or 3.5
terabytes of sequences
Population structure and admixture of indigenous African
cattle
Admixture dating: Main taurine x indicine admixture events in East African cattle date back to around 150 generation ago
(127 – 181), exception being Kenyan Boran and N’Dama, assuming a generation time of 5-7 years, it corresponds to 750 –
1050 years ago.
Signatures of selection analysis and signatures of selection ancestry
Identification of > 30 selective loci with an excess of taurine or indicine
ancestry underlying environmental adaptations, including heat
tolerance and water reabsorption
Unique selection signatures in African taurine
following their separation from the common ancestor with Eurasian taurine
Fst
Genome-wide PBS
Local PBS
Trypanotolerant locus
(a) Genome-wide distribution of PBS values with 50 kb window and 2 kb step. The dashed
line indicates top 0.1% PBS value. (b) Fst-based phylogeny among AFT, EAT and AAI. The
branch lengths are proportional to Fst values. (c) PBS values around the peak with the
highest PBS value. The PBS values were calculated with 5 kb window and 2 kb step.
CARD11: protein essential for the signalling of T and B
cells in innate and adaptive immunity, differentially
expressed between trypanotolerant N’Dama and
trypanosusceptible Kenya Boran (Noyes et al. 2011)
University of Seoul – ILRI - University of Nottingham
Zebu male-mediated introgression
consequence …..
2022
- ABC
simulation of
admixture,
indicates that
mito-nuclear
selection
needed along
with male-
biased Bos
indicus
introgression.
- Mito-nuclear selection signatures enriched with Bos taurus ancestry in African
Bos indicus cattle genome, the key expectation of the mito-nuclear
incompatibility hypothesis.
Taehyung Kwon et al. (2022)
See also Ward et al. 2022 iScience. https://doi.org/10.1016/j.isci.2022.104672
• RESILIENCE
• PRODUCTIVITY
• SUSTAINABILITY
2017
2020
2022
The future of African cattle
production
is in ancient indigenous
hybrids (composite)
https://www.ilri.org/publications/story-cattle-africa-why-diversity-matters
Acknowledgment (funding)
One CGIAR SAPLING Research Program on Livestock, International Livestock Research Institute
(ILRI), RDA Korea and University of Seoul (South Korea), Republic of China Government support to
ILRI – CAAS joint laboratory (Beijing), University of Nottingham (UK), Bill and Melinda Gates
Foundation, UK aid from UK Foreign Commonwealth and Development office both under the
auspices of the Centre for Tropical Livestock Genetics and Health (CTLGH) established jointly by the
University of Edinburgh, SRUC (Scotland’s Rural College).
The findings and conclusions contained within this presentation are those of the authors and do not
necessarily reflect the positions or policies of any of these institutions.
We are recruiting two Post-doctoral positions: Statistical Geneticist (poultry)
and Bioinformatician (livestock) o.hanotte@cgiar.org; t.dessie@cgiar.org

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The mosaic genome of African cattle: A unique adaptive genetic resource

  • 1. https://youtu.be/SFFdE0NsEe0 ILRI/Camille Hanotte The mosaic genome of African cattle: a unique adaptive genetic resource Olivier Hanotte & Sumaya Kambal TropAg2022 – HarlanIV 31st Oct – 2nd Nov 2022 Brisbane - Australia © ILRI/Camille Hanotte
  • 2. CIMMYT Mexico City Mexico IFPRI Wash. DC USA CIP Lima Peru CIAT Cali Colombia Bioversity International Rome Italy AfricaRice Cotonou Benin IITA Ibadan Nigeria ILRI Nairobi Kenya Addis Ababa, Ethiopia ICARDA Beirut Lebanon IWMI Colombo Sri Lanka IRRI Los Banos Phillippines WorldFish Penang Malaysia International Livestock Research Institute (ILRI) One of the 12 One CGIAR research centres ILRI is a CGIAR research centre, a global research partnership for a food- secure future. CGIAR science is dedicated to reducing poverty, enhancing food and nutrition security, and improving natural resources and ecosystem services.
  • 3. 3 Livestock Genetics – ILRI cattle, chicken, small ruminants The right genetics for the right environment Understanding & meeting farmer needs Climate is a key determinant of constraints – feed, disease, heat stress…… Adaptation Improved resilience, productivity, profitability, human nutrition Performance Reduced environmental impact, including reduced GHG intensity Mitigation
  • 4. Purpose: Within-breed selection of cattle adapted to predicted changes in the environment by studying the sensitivity of milk production to environmental conditions (feeding level and temperature humidity). 2009 But what about between breeds …..
  • 5. © Dan Bradley Kuri cattle, Lake Chad
  • 6. Cattle distribution (Felius 1995) African main agro-ecologies (HarvestChoice/IFPRI 2010)
  • 7. • There are at least 150 recognized indigenous African cattle ‘breeds’, a fifth of world’s cattle breeds; 300 million heads (Rege and Bester 1998; Dessie and Okeyo, 2019) Bos taurus ~8000 ya ~4000 ya Bos indicus ~1500 ya Ethiopian Boran White Fulani Fogera Tuli Nganda Red Fulani Mursi N’Dama Kenya Boran https://www.ilri.org/publications/story-cattle-africa-why-diversity-matters
  • 8. African Indigenous Cattle: Unique Genetic Resources in a Rapidly Changing World O. Mwai , O. Hanotte, Y-J Kwon, S. Cho (2015) Asian Asian - Autralasian Journal of Animal Sciences Example of African cattle adaptation ……. Etc……
  • 9. North – African sites with early presence of African cattle https://twitter.com/Physiologos/status/1564712371884621824/photo/1 © Jean-Loic Le Quellec (2022)
  • 10. X 2000 Science 2002 Bradley et al. PNAS 1996 Bofiglio et al. PloSOne 2012 Science 2002 D loop mtDNA 15 microsatellite loci One Y micro Dave Elsworth
  • 11. Köppen-Geiger Climate Classification Full genome high coverage sequencing of SNPs diversity OWSD – ILRI PhD fellow Sumaya Kambal
  • 12. Breed Abbrev. #IND Country Abergelle ABR 11 Ethiopia Afar AFR 9 Ethiopia Arado ARD 11 Ethiopia Arsi ARS 10 Ethiopia Bagaria BAG 10 Ethiopia Bale BAL 10 Ethiopia Begait BEG 20 Ethiopia ET-Boran EBO 40 Ethiopia Choke CHK 9 Ethiopia Erob ERB 8 Ethiopia Fogera FOG 9 Ethiopia Goffa GOF 9 Ethiopia Horro HOR 11 Ethiopia Mursi MUR 10 Ethiopia Ogaden OGD 9 Ethiopia Raya RAY 11 Ethiopia Semien SEM 10 Ethiopia KE-Boran KBO 16 Kenya Centre and West African zebu (CAZ) Breed Abbrev. #IND Country Aryashai ARY 10 Sudan Butana BUT 36 Sudan Gash GAS 8 Sudan Kenana KEN 30 Sudan Baggara BAG 19 Sudan Fulani FUL 10 Sudan Toupouri TOP 15 Chad Gudali GUD 1 Cameroon Red Fulani RFL 1 Cameroon White Fulani WFL 1 Cameroon Zebu Gobra ZGB 12 Senegal Zebu Maure ZMR 7 Senegal East African zebu (EAZ) 537 Samples Breed Abbrev. #IND Country Ghana Shorthorn GSH 10 Ghana Kapsiki KAP 1 Cameroon Namchi NAM 1 Cameroon Baoule BAO 16 Burkina Faso S-Muturu SMT 10 Nigeria F-Muturu FMT 13 Nigeria N’Dama GND 13 Gambia N’Dama NND 17 Nigeria N’Dama SND 12 Senegal N’Dama UND 21 Guinea African taurine (AFT) Breed Abbrev. #IND Country Gourounsi GOR 10 Burkina Faso Kuri KUR 10 Chad Sheko SHK 9 Ethiopia Djakkore DJK 11 Senegal Ankole ANK 10 Uganda African admixed (AAD) 45 Populations Köppen-Geiger Climate Classification
  • 13. MAF and LD pruned data 2,994,996 SNPs • MAF < 0.05 • r2 > 0.5 PC1 vs PC2 PC1 vs PC3 PC1: 62.7% PC2: 6.74% PC3: 5.86% PC1: 62.7%
  • 14. Population Admixture – K = 4 Zebu ancestries decreased as we move from East to the West Small shared Muturu and N’Dama taurine ancestry background (shorthorn/longhorn) within zebu (EAZ and CAZ) Treemix results
  • 15. PC2 (6.74%) separate CAZ from EAZ Centre and West African zebu (CAZ) East African zebu (EAZ) African taurine (AFT) PC3 (5.86%) separate longhorn taurine (N’dama) from shorthorn taurine (Muturu) CAZ EAZ Shorthorn Longhorn Fst: 0.196 between Savanna Muturu and Forest Muturu Fst: 0.227 between Savannah Muturu and N’Dama Guinea PC2: 6.74% PC3: 5.86%
  • 16. • Low genetic differentiation (Fst <= 0.01) within almost all EAZ and CAZ populations • Moderate genetic differentiation (Fst = 0.02 to 0.04) between EAZ and CAZ populations
  • 17. Entry points of the Zebu ancestral population on the African continent – Red Sea port Adulis (?) The Horn of Africa Adulis (Eritrea) R = - 0.88 R2 = 0.78 R = - 0.82 R2 = 0.67 Eastern Sahara (Nabta Playa) R = 0.68 R2 = 0.46
  • 18. 2010
  • 19. ‘’ I have often speculated on the probable cause through which each separate district in Great Britain came to possess in former times its own peculiar breed of cattle…..’’ ‘’… I conclude that, although slight differences in the nature of the climate, food, etc., as well as changed habits of life, aided by correlation of growth, and the occasional appearance from unknown causes of considerable deviations of structure, have all probably played their parts; yet the occasional preservation in each district of those individual animals which were more valued by each owner has perhaps been even more effective in the production of the several British breeds…’’ 1868
  • 20. 2017
  • 21. The genome landscape of indigenous African cattle J. Kim, O. Hanotte et al. (2017) Genome Biology
  • 22. Kim, Hanotte et al. Genome Biology 2017
  • 23. PRL - Senepol PRLR - Senepol PRLH – African Zebu
  • 25. Admixture characterization Admixture dating Signature of selection adaptation Signature of selection ancestry Candidate ancestral selected gene identification Identification of unique African ancestry candidates
  • 26. Whole-genome sequence analysis of 45 cattle breeds (16 indigenous African population, 172 animals), 35 billion reads or 3.5 terabytes of sequences
  • 27. Whole-genome sequence analysis of 45 cattle breeds (16 indigenous African populations), 16 indigenous, 35 billion reads or 3.5 terabytes of sequences Population structure and admixture of indigenous African cattle
  • 28. Admixture dating: Main taurine x indicine admixture events in East African cattle date back to around 150 generation ago (127 – 181), exception being Kenyan Boran and N’Dama, assuming a generation time of 5-7 years, it corresponds to 750 – 1050 years ago.
  • 29. Signatures of selection analysis and signatures of selection ancestry Identification of > 30 selective loci with an excess of taurine or indicine ancestry underlying environmental adaptations, including heat tolerance and water reabsorption
  • 30. Unique selection signatures in African taurine following their separation from the common ancestor with Eurasian taurine Fst Genome-wide PBS Local PBS Trypanotolerant locus (a) Genome-wide distribution of PBS values with 50 kb window and 2 kb step. The dashed line indicates top 0.1% PBS value. (b) Fst-based phylogeny among AFT, EAT and AAI. The branch lengths are proportional to Fst values. (c) PBS values around the peak with the highest PBS value. The PBS values were calculated with 5 kb window and 2 kb step. CARD11: protein essential for the signalling of T and B cells in innate and adaptive immunity, differentially expressed between trypanotolerant N’Dama and trypanosusceptible Kenya Boran (Noyes et al. 2011)
  • 31.
  • 32. University of Seoul – ILRI - University of Nottingham Zebu male-mediated introgression consequence ….. 2022
  • 33. - ABC simulation of admixture, indicates that mito-nuclear selection needed along with male- biased Bos indicus introgression. - Mito-nuclear selection signatures enriched with Bos taurus ancestry in African Bos indicus cattle genome, the key expectation of the mito-nuclear incompatibility hypothesis. Taehyung Kwon et al. (2022) See also Ward et al. 2022 iScience. https://doi.org/10.1016/j.isci.2022.104672
  • 34. • RESILIENCE • PRODUCTIVITY • SUSTAINABILITY 2017 2020 2022
  • 35. The future of African cattle production is in ancient indigenous hybrids (composite) https://www.ilri.org/publications/story-cattle-africa-why-diversity-matters
  • 36. Acknowledgment (funding) One CGIAR SAPLING Research Program on Livestock, International Livestock Research Institute (ILRI), RDA Korea and University of Seoul (South Korea), Republic of China Government support to ILRI – CAAS joint laboratory (Beijing), University of Nottingham (UK), Bill and Melinda Gates Foundation, UK aid from UK Foreign Commonwealth and Development office both under the auspices of the Centre for Tropical Livestock Genetics and Health (CTLGH) established jointly by the University of Edinburgh, SRUC (Scotland’s Rural College). The findings and conclusions contained within this presentation are those of the authors and do not necessarily reflect the positions or policies of any of these institutions. We are recruiting two Post-doctoral positions: Statistical Geneticist (poultry) and Bioinformatician (livestock) o.hanotte@cgiar.org; t.dessie@cgiar.org