Monday, January 9, 2012

Polymers: the not-so-secret Secret of Life. Part II. How it works

So, prompted by the recent BBC Radio 4 program, In Our Time, we blogged last week about polymers, long molecules made of strings of subunits.  Many naturally occurring polymers, and other physical structures like crystals, are built of large numbers of copies of the same subunit--the same type of atom, for example.  Even many of the substances produced by organisms, such as starches, are basically like that.

But the polymers of life, DNA, RNA, and proteins are different in a fundamentally important way.  They are constructed of chains of different subunits.

Life depends on the nature of heterogeneous polymers--made of arrangements of different chemical 'beads' in strings.  Life is a phenomenon of cooperation within the elements of and between, polymers.  One is DNA, with four types of bead, and another is proteins with 20 different types.  With just that knowledge alone, you couldn't tell whether the strings were from bacteria, fungi, plants, or animals.  The functional information in the string is based on the arrangement of the elements.

Conceptually, think of these as strings of pop-beads, as in this figure, that we just grabbed from the web:

The four colors correspond to the 4 nucleotide types in DNA.  These 'DNA-beads' can be strung together in any order, and for basically any length.  Now imagine a DNA molecule that is a pop-bead string that's 300,000,000 beads long, stretching for about 25 miles.  Now there will be various short strings (say, yellow-yellow-green, or blue-blue-blue) that are seen again and again, and correspond to some function.  That may be that they code for some particular amino acid (a 'bead' in a protein string of amino-acid pop-beads).  Proteins are similar but use 20 different bead colors, each with its own shape.  This is how DNA codes for the amino acid strings in proteins, and you can easily imagine that the order of individual beads, and of these small sequences of beads, carries the information in the DNA.  And thousands of different proteins, with their respective shapes are what carry out most of the jobs of life.  Not to be insulting, but the difference between you and a fungus is the set of these molecular shapes that you and it produce, and the sequence of the DNA that codes for them.

But there's more.  The beads of all types have the same knobs and sockets that allow them to chain together, but they are also of different shapes.  That's important.  So, for example, you can see that a green bead might fit into the depression in a blue bead.  So a string floating freely in a cell could fold up on itself, with blue-green 'bonds'.  The location of the blues and greens along the chain would determine where this folding occurred, and that in turn would give the self-folded chain a particular shape, and that shape could perhaps interact with the folded shapes of other, different strings.

Or, folded up molecules might patrol along a DNA-bead string, and wherever they found, say, blue-yellow-yellow-blue-red, they could stick to the shape of that bead sequence.  That could in turn attract other such molecules to the location.  This kind of bonding to DNA is what controls many of its functions: which nearby strings are made into RNA and then used to code for protein--that is, which of its genes a given type of cell uses, or into RNA that folds up upon itself as described above, giving it some function.

The point here is that with these shape-recognition features leading proteins and DNA to take shapes, and stick to parts of themselves or of other molecules based on these shapes, is the essence of how life works.  And why we say that life is a polymer phenomenon.  And it is all of these recognition-based interactions that give a cell or an organism its specificity.  And to do that, its countless components must be present in the right combinations at the right times.  That is, they must cooperate.

Messages are passed between cells that cause cells to change what they do, including which of their genes they use.  The message and the message-detector (signal and signal receptor molecules) are of the pop-bead type.  When the two join up, that triggers hundreds of other such interactions in the cell.  For the right messages to be passed, some cell somewhere must make and release the signal, and other cells must make the receptors and response molecules.  All of this is an exotic dance of similar cooperation.

To understand life this is what one must understand.  Variation in polymer arrangement leads to changes in function, and that can affect probabilities or rates of proliferation, and this of course is what evolution is all about.  A genetic change (mutation) is a change of the order of the DNA 'pop-beads', and if that leads to something that works, or works better under current circumstances, the change will be passed on to the next generation.  If some particular bead-order systematically confers an advantage, it may be transmitted more frequently than others in the population; that's what we call Darwinian natural selection.  But whether because of competitive advantage or just luck, different lineages of life accumulate different bead-orders, diverging more and more over time.

In this sense, that things have to be present together at the right time and place, in the right locations and combinations, makes life a logical phenomenon.  It's about presence and absence, combinations, arrangements, in space and time.  Since the same elements like signaling factors and their cell-surface receptors--the same substrings of pop-beads, can be used in different combinations to bring about different organs or structures, shows this rather clearly.  There's nothing physical about a signal factor or its receptor that resembles the physical structures of limbs or teeth, but the presence of the same factors, in different timing or combinations, is what makes these various structures.  And it is the differential use of these factors, triggered by signal-receptor combinations and regulatory protein-DNA binding, that makes different cell types (and, by extension, different species) what they are. Again, this shows that it is the logic rather than the specific physical traits that matter.  And this logic, combinations and arrangements, that is the essence of cooperation among the interacting elements that make an organism or a species or an ecosystem.  And all of this depends on, and is produced by, polymers made of non-identical 'beads'.

The discovery that evolution is a process of divergence from common ancestor, with the divergence increasing over time because of differential rates or patterns of proliferation of genomic variation--variation in the organisms among information-bearing polymers--has been perhaps more transformative than any other single realization in the history of science.   There are no 'paradigm shifts' involved, but there is a need for a rebalance of the central ideas or theory of life, to recognize that, yes, competition certainly does occur, but the essence of life is much more about cooperation, and it's the cooperation that comes first.

If you think of the huge numbers of cooperative interactions that must occur in the subset of  pop-bead strings that are involved in most individual biological traits, and that many different sets of strings can generate similar outcomes, then you can also see that, a cooperation-based view of life explains why even when natural selection is screening a function, there can be many ways to pass the screen, and any specific part of the system may be only very weakly affected by the selection.  That's why even when selection leads to specific functional adaptations, it's very hard to find solid evidence for it at the gene (pop-bead) level.

Again, understanding the nature of complex cooperation on which life is based, makes things fall into place more naturally than the oversimplified, competition-centered, often single-bead-focused view of life, that is so commonplace even among biologists (and certainly in the biomedical research world).  This is all ever so simple, and there's nothing secret or revolutionary about it. It's information available to anyone who wants to pay attention.  We think it's very important and that's largely why we wrote our book MT, to show its implications in detail.

Life is a polymer phenomenon.

1 comment:

BrerRabbi said...

What causes the cooperation? What motivator is present? What puts together the logical sequence in time and space and what for?

Once put together why would a sequence that provides no function on it's own not be eliminated by natural selection thus hindering complex systems from forming.

For instance a blood clotting system consists of many parts many of which which have no purpose on their own until all the parts are assembled. What preserves these sub systems until they are needed?

Elements do not have the intelligence to know the end purpose. Where does the design come from?

Chance interactions?

I could throw a piece of wood, a leather string and a piece of slate together forever and it would not assemble itself into the most primitive stone axe.

Why should it? The pieces have no knowledge or intelligence to know of the concept of a stone axe. And even if by some miracle they did assemble into a stone axe why would it stay that way without a wielder to use the axe and keep it together in that form.

Why do complex system assemble?