Mathematical models reveal how organisms transcend the sum of their genes
February 6, 2009 by Jill Sakai(PhysOrg.com) -- Molecular and cellular biologists have made tremendous scientific advances by dissecting apart the functions of individual genes, proteins, and pathways. Researchers at the University of Wisconsin-Madison College of Engineering are looking to expand that understanding by putting the pieces back together, mathematically.
John Yin, a professor of chemical and biological engineering, developed computer models of a relatively simple virus to show that genes alone do not make an organism. With mathematical representations of the virus's known biology, he and former graduate student Kwang-il Lim demonstrate how genomic organization and regulation can have a large impact on biological outcomes. As shown in a new paper, simply shuffling the order of the five genes in the virus's genome has a huge impact on how well the virus grows and how it interacts with its simulated host cell.
Their new results are reported Friday, Feb. 6, in the journal PLoS Computational Biology.
The eventual goal is to understand the full picture of how an organism's genome guides its growth and development, Yin says. "How does the biology of individual genes come together in genetic interactions to ultimately give rise to behavior?"
He and Lim, now a postdoctoral fellow at the University of California-Berkeley, computationally modeled the lifecycle of the vesicular stomatitis virus (VSV), a well-studied virus with only five genes and years of background research on its growth and function.
Virologists have previously created strains with 11 of the possible gene arrangements, but with their computational models, the Wisconsin researchers were able to simulate all 120 possible gene-order variants. Comparisons of the simulated strains revealed that the positions of the first and last genes are key to viral success.
The work has many potential applications. Understanding how to control the virus's growth and infectivity will help guide efforts to develop VSV as a cancer-targeting agent and create vaccines against more problematic viruses such as HIV-1 and influenza.
The models can also be used to investigate the genetic basis of other viral characteristics. For example, Yin is currently working to simulate drug effects on a virus to look for ways the virus can evolve drug resistance.
Ultimately he hopes his approach will scale up to more complex organisms with more complex genomes. For example, the completion of the Human Genome Project has inspired hopes of understanding how a person's genome determines their biology.
The era of such "predictive biology" is a long way off yet, Yin says, but the ability to identify key elements of genetic organization and regulation are a critical early step. "This establishes a foundation for linking a genome to developmental processes and ultimately to phenotypes or behavior of biological systems," he says.
More information: http://dx.doi.org/10.1371/journal.pcbi.1000283.
Provided by University of Wisconsin-Madison
Nov 12, 2009 |
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Genes Are Organisms, Earth's Primal Organisms
Recapitulation of few earlier posts
The evidence is obvious all around us, as we live and sleep,
just stop running and reflect a while...
A. Again and again, comprehension of the nature of Earth life:
Earth life: 1. a format of temporarily constrained energy, retained in temporary constrained genetic energy packages in forms of genes, genomes and organisms 2. a real virtual affair that pops in and out of existence in its matrix, which is the energy constrained in Earth's biosphere.
Earth organism: a temporary self-replicable constrained-energy genetic system that supports and maintains Earth's biosphere by maintenance of genes.
Gene: a primal Earth's organism. (1st-, base-, stratum organism)
Genome: a multigenes organism consisting of a cooperative commune of its member genes. (2nd stratum organism)
Cellular organisms: mono- or multi-celled earth organisms. (3rd stratum organism)
B. Again and again, the nature, origin, function and purpose of life
Nature of Earth life: a replicating construction temporarily constraining and maintaining energy.
Origin of Earth life: serendipitous energy-induced formation of Earth's primal organisms, individual independent genes.
Nature of Earth's organisms: temporary self-replicable constrained-energy genetic systems that support and maintain Earth's biosphere by maintenance of genes.
Function of Earth life: uphold and maintain as much constrained energy as possible by upholding and maintaining Earth's biosphere. (Probably one of several constrained energy forms, including black holes).
The purpose of OUR life and its promotion is ours to choose and set. It derives solely from our cognition, which is a biological entity.
The biggest hindrance of scientific and of technological progress in comprehension and exploitation of biology is the avoidance to accept-regard genes and genomes as organisms. Equally hindering is the avoidance to accept and to explicitly and clearly define genes as The Primal Base Cardinal Earth Life Organisms, the organisms that have been evolving into all other Earth organisms.
This avoidance, fraught with implications about human conception of the nature of life, is the biggest hindrance of human culture, of human existential and social progress.
C. Sleep, most obvious evidence of genes' life and their origin
Sleep made simple. Why do organisms sleep?
Sleep is an inherent Earthlife trait. Organisms sleep because their genes-genomes sleep. And for genes, sleep is inborn because genes were the first organisms evolved on Earth and they came into being, born, through the sun's radiation energy absorbed by RNA-type oligomers, and the newborn genes were active ONLY when exposed to sunlight, which was then - prior to bio metabolic energy production - their only usable energy. Thus sleep is an inherent Earthlife trait.
D. Chirality, most obvious evidence of genes' primal, base, status in life's evolution
Darwinian evolution started at life's day one, with the genesis of the first organisms, the replicating oligomers, pre-archaea genes. It started under yet-unknown energetic conditions, by a serendipitous accident, with oligomeric (RNA?) conformations, in a soup containing all their essential molecular progenitors. These conformations happened to absorb the amounts of energy enabling their polymerization to lengths precipitated as determined by the nature and conditions of the soup.
The sugars and the nitrogen-based compounds that, together with the phosphates, are the components of the genes organisms, are chiral. There probably is an energetic advantage in homochirality and chiral homogeneity for the self-replication of biopolymers.
This serendipitous accident set up a matrix-field of energy with a potential extended between its source, sun's radiation, and the precipitating organisms. This was the genesis of the ongoing formation and maintenance of Earth's biosphere.
And since thus the biosphere started it could only evolve in more favorable energetic directions and towards stabler components. Survival. Chiral organism survival. After all this was already into the process of life's evolution...
Dov Henis
(Comments From The 22nd Century)
Life's Manifest
http://www.the-sc...page#578
EVOLUTION Beyond Darwin 200
http://www.physfo...ic=14988&st=405&#entry396201
http://www.the-sc...age#1407