Building: Meyer

Tel: 972-8-934-3683

Fax: 972-8-934-4487

e-mail: doron.lancet@weizmann.ac.il

Mailing Address:
Prof. Doron Lancet
Weizmann Institute of Science
Department of Molecular Genetics

We study how evolution has generated the "olfactory sub-genome". This is the largest gene superfamily in human and other mammals, responsible for the sense of smell. More than a half of the ~500-strong olfactory receptor (OR) gene repertoire has been cloned and sequenced. A fully sequenced 0.5 megabase cluster with 16 OR genes on human chromosome 17 served as our model for genome and evolutionary analyses.

We have defined the intron-exon structure of a consensus olfactory receptor gene, and generated a molecular model for the OR hypervariable ligand binding site. We demonstrated that gene duplication and gene conversion underlie the augmentation of the OR germline repertoire.

In parallel, extensive pseudogene formation was shown to have led to a recent OR repertoire diminution. Extensive genetic polymorphism, analyzed by neutral mutation and selection theories, indicated a further diversification mechanism, and was correlated by genotype-phenotype linkage to inherited olfactory deficits.

A Receptor Affinity Distribution (RAD) model, developed to analyze olfactory recognition, was shown to be generally applicable to biological specificity and combinatorial chemistry. It also served as a basis for a novel approach to prebiotic evolution.

Parallel-computer simulations were used to analyze the kinetic behavior of mutually catalytic assemblies of lipid-like amphiphiles, characterized by a "compositional genome".

The demonstration that natural selection and chemical evolution could predate the appearance of RNA and protein biopolymers may resolve the "chicken and egg" problem of the Origin of Life.