Gene Logic: Finding your (micro)Identity

The secret to success in life is to find your identity, particularly if you are a cell. Achieving and holding an identity is the prime concern of life at its most fundamental, cellular level; it is the key to engaging in behavior which best meets the challenges and demands of the molecular thicket that is the environment of the cell. Life can downright bewildering on the micron level. An identity makes this world navigable. Identity determines how a cell looks, what it eats, and the company it keeps. It specifies what environmental signals can be received, and what responses those signals elicit. An E. coli bacterium metabolizing a favorite monosaccharide in your gut, a yeast cell looking to hook up with one of the opposite gender, a nerve cell in your brain primed for an electric response, that light-detecting rod cell in your retina, the myocyte harboring a molecular power train in your bicep, and a cancer cell gone rogue: each of these has at its core an identity that dictates its behavior.

A cell’s identity results from the confluence of different sources of information: information hard-wired into genomic DNA, lineage information inherited from a cellular parent, and information generated by signals in the environment. This information is processed and integrated, in an amazing feat of biological computation, resulting in a decision to assume an identity appropriate to the cellular environment, which can be the community of fellow cells that make up a human organ, or the nutritional, hydrational, and thermal challenges faced by free-living microbial cells. Because identity is the result of both genetic and more variable sources of information, identity can change over the life of a cell, and the same DNA, the same genome, can underlie many different identities. A bacterial cell can be primed to eat nutrient X or nutrientY. A yeast cell can readily undergo a sex change, and, after its gender identity is resolved, it can assume an identity appropriate for a life of metabolic luxury, or it can prepare itself to hunker down for lean times ahead. Many of us who are multi-cellular organisms start out as a mere single cell, a zygote, a fertilized egg, which divides into many cells, each of which must acquire the appropriate identity depending on where in the body it ends up. Some of those end up as stem cells, which have the potential to take on many different identities (making them extremely useful), while differentiated cells, like your neurons and muscle cells, have largely settled into their final identity for life. A cancer cell is one which has undergone an identity crisis; it has lost its previously established identity as a productive member of the body’s community (in this case, changes in DNA hard-wiring play a role), and now wreaks havoc as a confused cellular outlaw.

Assuming Identities: Cells take on many different shapes and sizes depending on their identities. Vertebrates like us produce such cell types as neurons (top left) and fat cells (top right). A free living yeast cell can also take on different identities: a nutritionally satisfied yeast cell (bottom left), and a starving, ‘pseudohyphal’ yeast cell (bottom right). Photo credits: neurons, http://brainmaps.org, via the Wikipedia Commons; adipocytes, Dept. Histology, Jagiellonian Medical College via the Wikipedia Commons; yeast cells, from Gimeno, et al., Cell 68:1077-1090 (1992).

What exactly does it mean for a cell to have an identity? Defining cellular identity, in the abstract at least, is straightforward. An identity means possessing a specific set of functional molecules, mostly proteins, that carry on the specialized jobs of each type of cell. A nerve cell, unlike a skin cell, can carry electrical signals because it possesses specialized protein pumps that move charged atoms in and out of the cell; a skin cell lacks these pumps, and has instead a set of specialized proteins that are lacking in the nerve cell. Your nerve and skin cells each have exactly the same DNA, your genome, but their protein machinery is different, because nerve and skin cells have their own identities. This definition of identity applies to free-living microbial cells as well. A yeast cell that is reveling in nutrients expresses a particular set of metabolic enzymes, nutrient sensors, and sugar uptake pumps; that same yeast cell, when it is starving, possesses a different set of proteins adapted to conserve energy and scavenge scarce resources. An E. coli bacterium living in the oxygen-poor environment of your colon contains one particular type of energy generating machinery, while E. coli living in an outdoor, oxygen-rich environment powers itself with an alternate set of proteins. Different identities entail different sets of specialized protein machinery that control a cell’s shape, metabolism, and ability to sense different environmental cues. Producing the right set of proteins is what identity is all about.

At this point it should be obvious that if we want to understand identity, this central feature of life, our challenge is then to understand how cells manage to process hard-wired and environmental information, and install the correct protein hardware. Don’t confuse this with the question of how proteins themselves are synthesized; that process is the generally same regardless of identity. More interesting is the decision-making process that chooses which proteins to make. This is the amazing act of biological computation that integrates information from different sources and settles on an identity. Since the instructions for making a particular protein is stored in the corresponding gene, having the right protein inventory essentially means having the proper set of genes switched ‘on’, while other genes are kept ‘off’. Patterns of genes flipped on and off are called patterns of gene expression, and biologists have discovered that an identity is established by establishing a pattern of gene expression. These patterns of gene expression are controlled by a remarkable process of DNA computing, executed by specialized regulator genes whose job is to turn genes on and off. The core of this computational process occurs when regulator genes regulate other regulator genes, which in turn regulate more genes. Genes regulating genes regulating genes: this is gene logic, and it is the key to cell identity, and thus at the heart of biology.

Gene logic is one of life’s major secrets. The rest of this series will be devoted to understanding how gene logic plays out inside of actual cells, how regulator genes controlling other regulator genes results in an identity that determines the biology of any given cell. To get there, we first need to understand 1) what it means for a gene to be on or off, 2) what it means for one gene to regulate another, and 3) how information coming from outside the cell reaches the hard-wired information encoded within DNA…. issues we will address in the next installment.

Author: Mike White

Genomes, Books, and Science Fiction

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