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Archives of Industrial Biotechnology | Volume 2
May 14-15, 2018 | Montreal, Canada
World Yeast Congress
T
he most deeply evolutionarily conserved human genes
encode essential cellular machinery whose failures are
linked to diverse diseases, from cancer to cardiovascular
disease. Recent systematic studies have discovered
extensive genetic polymorphism in these genes yet studying
how these variations contribute to cellular function and
overall human health remains a challenge. The remarkable
extent to which protein-coding genes are still functionally
equivalent between humans and yeast emphasizes the
power even of distant organism for studying human gene
function. We recently created hundreds of humanized yeast
strains (>200) such that human genes can complement a
lethal growth defect conferred by loss of the corresponding
yeast gene with little or no effect on growth. Humanizability
is not well-explained by sequence similarity between the
human and yeast genes but is instead a property of specific
protein complexes and pathways. We have further extended
this work replacing the entire set of shared essential genes
(>500 human genes) in yeast that have several co-orthologs
in humans assaying for functional complementation. We find
that duplicated human genes tend to differentially replace
their yeast ortholog, rarely observing broad ability to replace
within gene families. These results suggest that within-
species paralogs do indeed diverge in function at a higher
rate than between species orthologs. Thus, by extending
the scope of humanization assays to include those yeast
genes that have more than one human ortholog, we have
successfully added 90 new human genes to our tested set
(Total 310 - a 73% increase).
Speaker Biography
Aashiq H Kachroo did his PhD at the Indian Institute of Science, Bangalore, INDIA on the
molecular evolution of new functions in bacteria. He did his first postdoctoral training
at the University of Texas at Austin, USA with Dr. Makkuni Jayaram, studying the
mechanisms of site-specific DNA recombination. In his second postdoctoral research
at the University of Texas at Austin, USA with Dr. Edward Marcotte, he focused on
understanding deep homologies in essential genes across vast evolutionary distances
(yeast and humans) towards the development of humanized yeast. He is currently an
Assistant professor at Concordia University, Montreal, Canada. His research interests
span mechanisms of evolution of novel gene functions in bacteria, site-specific DNA
recombination, and ‘humanization’ of critical pathways in yeast.
e:
aashiq.kachroo@concordia.caHumanization of yeast genes with multiple orthologous human genes reveal principles of functional
divergence in paralogs
Aashiq H Kachroo
Concordia University, Canada