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Last week we explored the central dogma of biology: the fact that every living thing on the planet without exception is linked by a common means of storing, expressing, and passing on hereditary information in the form of DNA. This DNA is replicated and passed faithfully on to offspring during cell division, and also transcribed to RNA and then translated to protein in a nearly identical process in every living organism during gene expression.

Given that DNA is a universal feature of all life forms, it is natural to wonder if proteins, which are encoded by that DNA, also have general features that all living things share. The answer is a resounding yes: not only are many of the basic features of proteins conserved among all known life, many entire proteins themselves are so well conserved in structure and function that they are interchangeable between organisms as different as yeast and humans.

To understand what it means for a protein to be conserved, let’s begin with an overview of what proteins are and what they do.

Proteins are the incredibly complex molecular machines encoded by your genetic material that facilitate nearly all of the chemical reactions in your cells required for life. Whether taking up and breaking down nutrients, expelling waste, repairing cellular damage, moving around cellular components, or defending the body against invading entities, proteins are the key players. The genes in your DNA encode proteins by dictating the order in which the twenty different amino acids available in your cells are strung together, producing a long polymer often several thousand units long. This polymer then folds up based on the chemical properties of the twenty amino acids: some are positively or negatively charged, and some are hydrophobic (water fearing) or hydrophilic (water loving). Therefore, in the aqueous environment of the cell, a protein will spontaneously fold into a complex three-dimensional shape dictated by its primary sequence: hydrophobic regions will cluster inside the core of the protein, shielded from surrounding water, hydrophilic regions will decorate the surface, and different points of the chain will be electrically repelled or attracted to one another. The end result is a functional protein: usually a globular mass made up of a long string (think of a pair of really tangled headphones).

There is something extremely elegant about this seemingly random tangle of amino acids. While from our visual perspective proteins may seem like rather irregular globs, from a chemical point of view, proteins are the most functionally sophisticated and structurally complex molecules in the known universe, often capable of carrying out a specific function or series of functions many hundreds of thousands of times per second. The majority of proteins act as enzymes, that is, they catalyze key biochemical reactions by binding a specific chemical component (called a ligand) and facilitating some sort of reaction on it.

The binding site on the protein is often a specific surface patch that is just the right shape to facilitate both binding and the chemical reaction. In fact, this binding site is often so specific that changing a single amino acid in the protein (remember they often are made up of many thousand amino acids), even one on a completely different area than the binding site, is enough to completely destroy a protein’s biochemical function. The result is often detrimental or even deadly to the organism with the mutated protein.

For instance, the genetic condition cystic fibrosis is often caused by a single amino acid substitution that is not overly close to the binding site. Considering that the pressures of natural selection have been fine-tuning protein structure for over 3 billion years of evolutionary history, it is perhaps not surprising (although still astonishing) that their structure and function are so powerfully intertwined.

The potent link between protein structure and function has fascinating consequences when we consider that many of the basic biochemical tasks of a cell are the same whether performed in a single cellular fungus or one of the trillions of cells in a human body. For instance, all living things require proteins capable of binding DNA to regulate when genes are expressed (actively used to produce protein). We may suspect that a protein carrying out this function in very different organisms would look rather similar.

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Indeed, as far back as 1991, structural biologists were able to show that an important protein structure involved in gene expression, called a homeodomain, is nearly identical in yeast and flies despite being separated by more than a billion years of evolutionary divergence.

Based on structural analysis, we know that the yeast and fly homeodomain are likely similar because they come from a common ancestor. In other words, an organism living over one billion years ago, before single celled eukaryotes and multicellular insects diverged evolutionarily, must have had a protein that looked a lot like the modern homeodomain, likely carrying out a similar function.

Since this protein was so important for survival, any mutation to the homeodomain in either the fly or yeast lineage that damaged function would lead to a sick or deceased individual incapable of passing on its genes. Such proteins, which are structurally similar between very different organisms, are called homologs.

The story of the homologous homeodomain protein is just one of thousands that could be told to demonstrate the extreme structural and functional similarity of proteins in evolutionarily divergent organisms. It is estimated that the human genome includes some 21,000 protein encoding genes. As the structure and functions of these are identified by future generations of researchers, we will likely find more surprising ways our proteins provide a universal link for life on earth.

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