Josh: Dr. Marth brings up some very good points. Many signaling molecules in cells are not just composted of proteins, but may be molecules that are a combination of protein and sugar (glycoprotein) or protein and fatty acid. Fatty acids alone may be signaling molecules, such as fatty acid derived prostanoids via cyclooxygenase (COX) that play a role in pain signaling. Since these molecules are created by enzymes, studying the genome or proteome alone is not sufficient to understand diseases caused or influenced by defects in them.

Why is it that the origins of many serious diseases remain a mystery? In considering that question, a scientist at the University of California, San Diego School of Medicine has come up with a unified molecular view of the indivisible unit of life, the cell, which may provide an answer.

Reviewing findings from multiple disciplines, Jamey Marth, Ph.D., UC San Diego Professor of Cellular and Molecular Medicine and Investigator with the Howard Hughes Medical Institute, realized that only 68 molecular building blocks are used to construct these four fundamental components of cells: the nucleic acids (DNA and RNA), proteins, glycans and lipids. His work, which illustrates the primary composition of all cells, is published in the September issue of Nature Cell Biology.

Like the periodic table of elements, first published in 1869 by Russian chemist Dmitri Mendeleev, is to chemistry, Marth’s visual metaphor offers a new framework for biologists.

This new illustration defines the basic molecular building blocks of life and currently includes 32 glycans (sugar linkages found throughout the cell) and eight kinds of lipids (which compose cell membranes) along with the more well-known 20 amino acids that are used to make proteins and the eight nucleosides that compose the nucleic acids, DNA and RNA.

“These 68 building blocks provide the structural basis for the molecular choreography that constitutes the entire life of a cell,” said Marth. “And two of the four cellular components are produced by these molecular building blocks in processes that cannot be encoded by the genes. These cellular components – the glycans and lipids – may now hold the keys to uncovering the origins of many grievous diseases that continue to evade understanding.”

Currently, the vast majority of medical research looks to the human genome and proteome for answers, but those answers remain elusive, and perhaps for good reason.

“We have now found instances where the pathogenesis of widespread and chronic diseases can be attributed to a change in the glycome, for example, in the absence of definable changes in the genome or proteome,” Marth said, adding that, as biomedical researchers, “we need to begin to cultivate the integration of disciplines in a holistic and rigorous way in order to perceive and most effectively manipulate the biological mechanisms of health and disease.”

“What is important is that no one has composed it and laid it out so clearly before,” said Ajit Varki, M.D., Distinguished Professor of Medicine and Cellular and Molecular Medicine and founder and co-director of the Glycobiology Research and Training Center at UC San Diego School of Medicine, and chief editor of the major textbook in the field, The Essentials of Glycobiology. “Glycobiology, for example, is a relatively new field of study in which researchers at UC San Diego have much expertise, and Dr. Marth’s work further illustrates the importance of these glycan molecules.”

Marth believes that biology should become more integrative both in academic and research settings. “I’m one who believes that we don’t need to sacrifice breadth of knowledge in order to acquire depth of understanding.”

Source: University of California - San Diego

A unified vision of the building blocks of life. Jamey D. Marth. Nature Cell Biology. September 2008 - Vol 10 No 9. doi:10.1038/ncb0908-1015

Slobodan Cekic writes in response to How Much Data is a Human Genome:

Now, please do take a look at your fingertips. You ll see the fine lines of your fingerprint pattern. It is unique, and can be used to identify a human; so fine and even much finer structures are defined in your organism.
Now, how high would be only 3D positional information content needed to describe a human?

You would need to position single cells, define the inner structure of particular cell types, describe the form of single nerve cells (dendrites)…etc

Now how many cells are there in the human organism?

Without any calculation, we can see the information quantity to describe a human in uncounted Terabytes. Human chromosomes contain , as calculated here, 740 MB.

So, why for the God’s sake do we believe that the whole of our hereditary information resides in the genes?

740MB is the size of a reference human haploid nucleotide base string, not the data necessary to describe a mature human.

We believe that most of our hereditary information resides in genes because it does. However, a genome, as you say, cannot possibly fully describe a mature human. A genome is more like a brief mathematical equation used to produce beautifully complex fractal design when fed with ambient noise and interpreted as colors and coordinates on a screen.

Arguably, as other commentators have noted, this isn’t enough to describe a genome. Cytosine can be methylated —like a fifth base. Sometimes, a sequencing machine is unable to assert a base, and an extra bit would necessary to report these “no calls.”

But in reality, humans don’t have a “reference genome.” Almost every cell has its own pair of genomes, and these tend to diverge as they accumulate mutations and errors. To be pedantic, to record your Real and Complete Human Genome, one would have to sequence every strand of DNA in your body instantaneously.

Yet, these trillions of strings of millions of bases can be understood as that 740MB reference human genome like a field full of flowers can be understood as a photo of daisy.

A nationwide consortium led by the University of Washington in Seattle has completed the first sequence-based map of structural variations in the human genome, giving scientists an overall picture of the large-scale differences in DNA between individuals. The project gives researchers a guide for further research into these structural differences, which are believed to play an important role in human health and disease. The results appear in the May 1 issue of the journal Nature.

The project involved sequencing the genomes of eight people from a diverse set of ethnic backgrounds: four individuals of African descent, two of Asian descent, and two of European background. The researchers created what’s called a clone map, taking multiple copies of each of the eight genomes and breaking them into numerous segments of about 40,000 base pairs, which they then fit back together based on the human reference genome. They searched for structural differences that ranged in size from a few thousand to a few million base pairs. Base pairs are one of the basic units of information on the human genome. … Continue Reading »