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SUMMARY:An experimental assay of the genotype to phenotype connection. - D
 r Fyodor Kondrashov\, Centre for Genomic Regulation in Barcelona 
DTSTART:20160121T140000Z
DTEND:20160121T150000Z
UID:TALK62040@talks.cam.ac.uk
CONTACT:Caroline Newnham
DESCRIPTION:The nature of the genotype to phenotype connection\, the fitne
 ss landscape\, remains poorly understood. In my talk I will first present 
 a review of why this question is particularly relevant for molecular evolu
 tion. The rest of the talk I will focus on an experimental assay of the fi
 tness landscape of a specific protein\, the GFP\, We assayed the GFP nativ
 e function\, fluorescence\, of tens of thousands of genotypes allowing us 
 to characterize its fitness landscape including genotypes with multiple mu
 tations. We find its fitness landscape is locally narrow\, with half of ge
 notypes two mutations from the wildtype showing reduced fluorescence and f
 luorescence completely eliminated in half of genotypes with five mutations
 . The narrowness is enhanced by epistasis\, which was detected in 30% of g
 enotypes. Complex interactions were present in 1/6 genotypes\, blocking 20
 % of the paths between fluorescent genotypes\, demonstrating substantial r
 uggedness of the fitness landscape. A model of orthologous sequence diverg
 ence spanning hundreds of millions of years predicted the extent of epista
 sis in our data\, indicating congruence between the local and global evolu
 tionary scales of the fitness landscape. Time permitting\, I will present 
 data on an ongoing project involving an assay of the fitness landscape of 
 two interacting proteins.
LOCATION:Biffen Lecture Theatre\, Department of Genetics\, Downing Site
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