Biodiversità animale e sistemi zootecnici Alessio Valentini 13/04/2010 Accademia Nazionale delle Scienze detta dei XL.

Biodiversità animale e sistemi zootecnici

Alessio Valentini

13/04/2010 Accademia Nazionale delle Scienze detta dei XL

13/04/2010 Accademia Nazionale delle Scienze detta dei XL

Comparisons of domesticated wild species (left of each pair) and their never-domesticated close relatives (right) reveal the subtle factors that can derail domestication. J. Diamond, Nature 2002

13/04/2010 Accademia Nazionale delle Scienze detta dei XL

•a diet not easily supplied by humans (hence no domestic anteaters),•slow growth rate and long birth spacing (for example, elephants and gorillas), •nasty disposition (grizzly bears and rhinoceroses),• reluctance to breed in captivity (pandas and cheetahs),• lack of follow-the-leader dominance hierarchies (bighorn sheep and antelope), •and tendency to panic in enclosures or when faced with predators (gazelles and deer, except reindeer)

Rules for animal domestication

13/04/2010 Accademia Nazionale delle Scienze detta dei XL

The mystery of Etruscan origins: novel clues from Bos taurus mitochondrial DNAMarco Pellecchia,1 Riccardo Negrini,1 Licia Colli,1 Massimiliano Patrini,1 Elisabetta Milanesi,1† Alessandro Achilli,2 Giorgio Bertorelle,3 Luigi L Cavalli-Sforza,4 Alberto Piazza,5 Antonio Torroni,2 and Paolo Ajmone-Marsan1*

Proc Biol Sci. 2007 May 7; 274(1614): 1175–1179.

Published by AAAS

B. Chessa et al., Science 324, 532 -536 (2009)

Fig. 2 Combination of enJSRV proviruses (retrotypes) in the domestic sheep

Published by AAAS

B. Chessa et al., Science 324, 532 -536 (2009)

Fig. 3 Genetic distances between sheep populations on the basis of enJSRVs insertion frequencies

13/04/2010 Accademia Nazionale delle Scienze detta dei XL

Lactose intolerance by region (African countries are only a rough guess). Red indicates a high percentage of intolerance, green a low percentage. Wikipedia.org

13/04/2010 Accademia Nazionale delle Scienze detta dei XL

Approximate posterior density of region of origin for LP/dairying co-evolution.Itan Y, Powell A, Beaumont MA, Burger J, Thomas MG, 2009 The Origins of Lactase Persistence in Europe. PLoS Comput Biol 5(8)

11

Central Dogma of GeneticsCentral Dogma of Genetics

Breeds of cattle

Why so many colors?

C33Tred chicken

(Takeuchi, 1996)

S83Fchestnut horse

(Marklunk, 1996)

R151Cred hair(Rees, 1997)

A240Tred pig

(Kijas, 1998)

G104red cow

(Klungland, 1995)C183

yellow mouse(Robbins, 1993)

R306terIrish Setter

(Newton, 2000)

Molecular causes of Mc1r loss-of-function

Leptin - fat deposition

DGAT1 – milk production and fat

BHGR – milk components

Thyroglobulin - marbling

Calpastatin - tenderness

Calpain - tenderness

Somatostatin -- marbling

Important genes affecting production traits

Myostatin (double muscling)

Belgian blue

Double Muscling in cattle

Piemontese

Marchigiana

• General increase in muscle mass– Muscular Hyperplasia

• up to 86% increase in muscle fibers

– and Hypertrophy• up to 20% increase in fiber

diameter

GDF8 +

GDF8 -

Effect of abolishing GDF8 expression

The way from DNA to functional proteins is much longer than envisaged by the “central dogma”!

Topic 8-2 20

• Repression of Transcription - Mechanisms:– Binding to

promoter elements• Blocking assembly

of the preinitiation complex

Control of Gene Expression

Topic 8-2 21

• Repression of Transcription - Mechanisms:– Inhibiting binding

or functioning of transcriptional activators

Control of Gene Expression

Topic 8-2 22

• Repression of Transcription– DNA Methylation• Methyl groups may be attached to cytosine

(C5 position)– Methyltransferases

• Methyl groups provide a tag • In mammals always part of a symmetrical

sequence• Concentrated in CG-rich domains

– Often in promoter regions

• Methylation of promoter DNA highly correlated with gene repression

Control of Gene Expression

Callipyge

• “Beautiful buttocks”• A mutation which

arose in a Dorset Ram• “Polar

Overdominance”

Polar overdominance

• Heterozygote expresses the phenotype but neither homozygote does

• Heterozygote only expresses the phenotype if the mutant gene is inherited from the father

Positional identification of genes influencing muscle mass …

« Double-muscled » Belgian Blues: MSTN KO

Hypermuscled Piétrains: IGF2 upregulation

Callipyge sheep:Ectopic DLK1 expression polar overdominance

Hypermuscled Texel:Patrocles mutation

miRNAbiology

A QTL affecting muscle mass maps to OAR2 …

Chromosome 2

Texel sheep produce normal levels of normal MSTN mRNA

• Sequencing the MSTN ORF from gDNA & cDNA:– no polymorphism.

• Northern blot and qRT-PCR:– no obvious qualitative or

quantitative difference.

Resequencing the MSTN gene identifies 20 non-coding SNPs …

3 Texels – 7 controls

G+6723G-A reveals one of « Kellis’s octamer motifs » …

G

-central role of Dicer in RNAi pathway

-cleaves 2nt-3´-overhang-dsRNA; endogenous (pre-miRNA) and exogenous dsRNA into miRNA and siRNA

-products interact with RISC for sequence-specific gene-silencing

Genomic Sequencing

Launch: Dec. 2003Expected Finish: Spring 2007

International Collaboration

– NIH / NHGRI -- $25M– State of Texas – $10M– USDA -- $11M– Australia -- $1M– Genome Canada -- $5M – New Zealand -- $1M– Beef Councils (US, TX, SD) – $0.82M

Project Total = $53M

SNP Discovery in the Genome Age

...AGCTTTAAGCCATACCTTAGGACATTACCTAGG GCCATACCTTAGGACATTACCTAGGAGCTTTAAGCCATAC......AGCTTTAAGCCATACCTTAGGACATTACCTAGGAGCTTTAAGCCATAC......AGCTTTAAGCCATACCTTAGGACATTACCTAGGAGCTTTAAGCCATAC......AGCTTTAAGCCATACCTTAGGACATTACCTAGGAGCTTTAAGCCATAC......AGCTTTAAGCCATACCTTAGGACATTACCTAGGAGCTTTAAGCCATAC...

...AGCTTTAAGCCATACCTTAGGACATTACCTAGGAGCTTTAAGCCATAC...

...AGCTTTAAGCCATACCTTAGGATATTACCTAGGAGCTTTAAGCCATAC...

SNPMartha

Dominette

Consensus

Genomic selection

Predicted EBV

TrainingEBV

Gain from genomic selection

13/04/2010 Accademia Nazionale delle Scienze detta dei XL

13/04/2010 Accademia Nazionale delle Scienze detta dei XL

Cattle breed Country PeriodCensus

population sizea

Effective population size (Ne)

Reference

Holstein Denmark 1983-1992 - 68Sørensen et al.

2005

Holstein Germany 1999 ≈ 2,200,000 52Koenig &

Simianer 2006

Holstein Denmark 1993-2003 ≈ 3,700,000 49Sørensen et al.

2005

Holstein France 1988-1991 (?) ≈ 2,500,000 46Boichard et al.

1996Holstein USA 1999 ≈ 8,500,000 39 Weigel 2001

Jersey Denmark 1977-1991 - 87Sørensen et al.

2005

Jersey Denmark 1993-2003 ≈ 640,000 53Sørensen et al.

2005Jersey USA 1999 ≈ 550,000 30 Weigel 2001

Danish red Denmark 1977-1998 - 157Sørensen et al.

2005

Danish red Denmark 2001-2003 ≈ 560,000 47Sørensen et al.

2005

Japanese black Japan 1986-1990 - 30Nomura et al.

2001

Japanese black Japan 1993-1997 ≈ 530,000 17Nomura et al.

2001

Montbéliarde France 1988-1991 (?) ≈ 700,000 125Boichard et al.

1996

Abondance France 1988-1991 (?) ≈ 65,000 106Boichard et al.

1996

Normande France 1988-1991 (?) ≈ 800,000 47Boichard et al.

1996

Tarentaise France 1988-1991 (?) ≈ 14,000 27Boichard et al.

1996

Taberlet P, Valentini A., Rezaei Hr, Naderi S, Pompanon F, Negrini R, Ajmone-Marsan P. (2008). Are cattle, sheep, and goats endangered species?. Molecular Ecology. vol. 17(1), pp. 275-284