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Hidden gene variation drives evolution

Understanding how complex mutations in genes drive disease and evolution...

Identifying complex mutations in the structure of an organism's genome is difficult. But in a new study published online in Nature Genetics, a research team led by J.J. Emerson PhD, assistant professor of ecology & evolutionary biology at the Ayala School of Biological Sciences, uses new methods of genome analysis to identify complex mutations with unprecedented image resolution.

His team's approach identified extensive genetic variation in the fruit fly which previously had escaped attention. Researchers hope these results will help others understand how complex mutations not only drive disease, but also evolution.

"For the first time in animals, we have assembled a high-quality genome, permitting the discovery of all the genetic differences between two individuals within a [single] species. We uncovered a vast amount of hidden genetic variation during our analyses, much of which affects important traits within the common fruit fly, Drosophila melanogaster."

Mahul Chakraborty, postdoctoral scholar, J. J. Emerson Laboratory, Department of Ecology and Evolutionary Biology, University of California, Irvine, CA, USA, and first author on the study.

Unlike standard approaches that rely on the same sequencing technology that delivered the so-called $1,000 genome, the team relies on reconstructing the whole genome using a newer technology capable of reading much larger pieces of the genome. The use of long molecule sequencing gave Chakraborty and Emerson the opportunity to unravel complex changes as they alter the structure of the genome.
"This study is the first of its kind in complex organisms like the fruit fly. With this unique resource in hand, we have already characterized several candidate structural variations which show evidence for phenotypic [individual characteristic] adaptation, that can function to drive a species evolution."

J. J. Emerson PhD, Professor, Department of Ecology and Evolutionary Biology, University of California, Irvine, California, USA.

Exploring how some of these newly identified genome changes contribute to fruit fly evolution, the group was drawn to an enzyme family associated with the fly's resistance to pesticides and cold temperature. In the fruit fly, D. melanogaster, they found structural changes crank up the output of one of the genes by 50-fold, suggesting a way flies may increase their own nicotine resistance.
According to the research, the fact that so much variation escaped notice in D. melanogaster, a species with relatively simple genomes that are less likely to hide variation, suggests our own genomes and those of species we eat, are harboring an even larger store of medically and agriculturally important genetic variation.

Mutations that add, subtract, rearrange, or otherwise refashion genome structure often affect phenotypes, although the fragmented nature of most contemporary assemblies obscures them. To discover such mutations, we assembled the first new reference-quality genome of Drosophila melanogaster since its initial sequencing. By comparing this new genome to the existing D. melanogaster assembly, we created a structural variant map of unprecedented resolution and identified extensive genetic variation that has remained hidden until now. Many of these variants constitute candidates underlying phenotypic variation, including tandem duplications and a transposable element insertion that amplifies the expression of detoxification-related genes associated with nicotine resistance. The abundance of important genetic variation that still evades discovery highlights how crucial high-quality reference genomes are to deciphering phenotypes.

Authors: Mahul Chakraborty, Nicholas W. VanKuren, Roy Zhao, Xinwen Zhang, Shannon Kalsow and J. J. Emerson

Other contributors: Roy Zhao, Xinwen Zhang and Shannon Kalsow from UCI, and Nicholas VanKuren from the University of Chicago.

The study was supported by the National Institutes of Health, The University of California, Irvine, CA, USA (UCI) and the National Science Foundation.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. It's located in one of the world's safest and most economically vibrant communities and is Orange County's second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit http://www.uci.edu.

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Jan 1, 2018   Fetal Timeline   Maternal Timeline   News   News Archive

Distribution of structural variants (SVs) across chromosome arms of the A4 genome. Track 1 shows pericentric heterochromatin (black). Tracks 24 show transposable elements (TEs), duplicate Copy number variations (CNVs) (relative to ISO1), and non-TE indels >100 bp in length, respectively. CNVs and TEs are present in higher densities in heterochromatin as compared to euchromatin; whereas non-TE indels have less heterochromatin. Image credit: University of California Irvine, CA. USA.

Phospholid by Wikipedia