Comparing the general organization of the bodies of living and extinct organisms shows evidence of both lineal relationships and improvisation. Likewise, the DNA of organisms tells the same story. However, nature's genetic tinkering has some tragic consequences.
DNA isn't so much a blueprint, but a recipe for a creature. Blueprints are paper representations, drawn models, of structures. Recipes specify the steps required to perform a task and the necessary ingredients.
Imagine inheriting a large file box of family recipes used in preparation of a traditional, grand meal. There are many courses. Each dish is elaborate, requiring preliminary preparations and many ingredients. For the entire meal to be successful, each course must be prepared and ready at a specified time. The steps for each dish's preparation are explicitly laid out on sequential 3-by-5 cards.
The first and last card for each sequence of tasks is uniquely marked. For the meal to come off as desired, coordination is important. Steps required for some dishes must begin before tasks are completed on other dishes.
Ingredients and preliminary products must be ready when needed. To achieve the necessary coordination, at the end of many tasks, cards are copiously cross referenced. These initiate tasks in preparation of other courses.
This great meal came about through trial and error. Over many generations, marriage has brought in new family members with new recipes. The meal has transformed as the result of changing traditions and tastes and availability of ingredients or new cooking methods.
While useful recipes and tasks were maintained and improved upon, some old dishes were completely abandoned. On other occasions, old recipes were modified and adapted to new dishes.
To accommodate the ever expanding family, the complete deck of cards has been copied many times. Some cards have accumulated typos. Other cards are nearly illegible from smudges. Consequently, there are several versions of the meal.
Unfortunately, cards from old, abandoned recipes have been misplaced in the box and randomly mixed between tasks still being preformed. In fact, useful cards only represent a very small fraction of all the cards.
Though the meal is sumptuous, the accumulated errors and jumbled instructions have made the meal preparation rather messy and inefficient. A great deal of effort is wasted working through the junked recipes and maintaining the file's bloated contents.
The human genome is not unlike the recipe file box described above. Genes in DNA provide explicit instructions for fabricating proteins, just as tasks are specified on recipe cards. The beginning and end of a set of instructions on a strand of DNA is clearly identified.
The steps outlined can only start when all ingredients and preliminary products are ready. So, there is copious cross referencing (signaling) to assure proper timing. Many proteins produced by DNA are themselves signals to start brewing up other proteins (ingredients) elsewhere.
As cross-referenced recipe cards signal the need to start a new task, some proteins act as signals. They coordinate expression of multiple genes. Some of these result in transformation of generic cells into specialized cells. Stretching the analogy a bit, this is like directing the use of salt, sugar, and flour to make a variety of products such as bread or pie crust.
Similarly, genomes of complex organisms grew and became more complex through trial and error. New genes have been adopted through mating. A variety of gene mutations occur, often during copying (typos) or from environmental influences (smudges).
Many old genes have been abandoned. "Junk DNA" makes up about 98 percent of the human genome. This can make translating DNA (preparing the meal) a messy and inefficient affair. On occasion old genes are resurrected for new tasks.
Just as examination of our recipe file reflects its long history; DNA displays the history of an organism's lineage. The genetic makeup of all creatures reflects the range of conditions previously experienced by ancestral organisms.
Complex organisms are truly grand, but they are fraught with problems. There is a long list of human disabilities and disease whose origin can be traced directly to weak links in the genetic code and its networking operations.
A wonderful meal can become a mess if important ingredients are missing, the oven breaks or recipe cards get lost or misread. So too, genetic frailties are exposed at nearly every step in the copying and expression of genes.
Mutations can cause loss of essential signals that start processes. Or, they can cause fabrication of aberrant proteins. Misshapen proteins can bring essential metabolic process to a halt.
One example of a metabolic disorder of genetic origin is cystic fibrosis. It occurs in about one in 2,500 births. It results from any one of 800 mutations of a gene that encodes a protein known as CFTR. CFTR regulates uptake of salt by cell membranes.
Genomic research has accelerated tremendously in the past several decades, giving us growing insight. The most recent edition of The Metabolic and Molecular Bases of Inherited Disease is 6,000 pages in length. More than 500 genetic disorders are described in this publication.
Learning how the human genome is cobbled together, and how it goes wrong, gives hope for discovering interventions to mitigate the devastating effects of genetic flaws.
Steve Luckstead is a medical physicist in the radiation oncology department at St. Mary Medical Center. He can be reached at firstname.lastname@example.org.