Drew Berry introduces us to the fascinating world of molecules. Since the invention of X-ray crystallography our depth of understanding the molecular nature of things have skyrocketed. Year 2012 marked the centennial of the discovery of X-ray chrystallography by the Australian physicist William Lawrence Bragg who shared the Nobel Prize with his father in 1915. The technique was so powerful that since its discovery, it generated 28 Nobel Prizes including the discovery of DNA. the famous X-ray chrystallographical image #51 was pivotal in understanding helical structure of DNA. Thanks to X-ray chrystallography today we can analyze the structures of complex molecules and their interactions with others in exquisite detail.
This short lecture does two things quite successfully. First, it exposes us to DNA replication machinery (DNA polymerase). Drew Berry’s animation is a wonderfully accurate visualization of how one of the essential molecules of life replicates. Secondly, Drew Berry’s animation shows us how the duplicated DNA becomes packaged in nucleosomes. Nucleosomes are organized to form chromosomes. After their duplication chromosomes get separated neatly with the help of spindle fibers (microtubules) and motor molecules called kinesins. Each copy of chromosomes are pulled towards the daughter cells. This separation is critical for healthy cell division. Cell division is responsible for reproduction, development, growth and repair.
DNA packaging into chromatin via histone proteins forming nucleosomes. This is no trivial thing. Nucleosome wrapping of DNA determines one of the major evolutionary transitions into multicellularity. Placement of the first nucleosome in a gene is a major distinction between unicellular and multicellular life.
Once all components of a living system is studied, it is imperative to show how the whole works. Realistic representations of molecules becomes essential in this endeavor. For instance –The Central Dogma– by RIKEN Institute distills knowledge gathered by scientists for over more than half a century into 15 minutes. Similarly, another animation details light reactions of early anoxic photosynthesis taking place in the purple bacteria. The BBC documentary The Hidden Life of the Cell illustrates a real scenario of adenovirus infection. Visualization of molecular structures helps us understand or predict the functions of genes. Scientists have compiled large databases based on experimentally determined structures.
One of the turning points in Human cultural evolution is the practice of Agriculture. Archeologist for a very long time found overwhelming evidence that it started by selection of non-shattering seeds. Our ancestors initially were not concerned about the size of the grain. At the beginning harvestability was the most important trait. Now we can pinpoint what kind of genetic mutations enabled this peculiar trait in plants by analyzing molecular structures of the mutated proteins these altered genes produce.
Non-shattering forms have been observed in many domesticated plants such as rice, wheat, maize and sorghum. These varieties arise mostly through a mutation in a type of gene called transcription factor which also control expression of other genes in a cascading manner.
In sorghum for example, non-shattering seeds in domesticated variety (Sorghum bicolor) is conferred by a mutation in a transcription factor called WRKY. In the video below sections of the both wild (right) and domesticated (left) sorghum WRKY transcription factors are shown. Conserved WRKY DNA binding domains are visualized as ball and stick representations on both models. In wild sorghum (S. propinquum) first 144 amino acid is shown in red. In domesticated sorghum this section is deleted due to a mutation that moves the start codon to a later position. First beta sheet in wild sorghum (red arrow) intercalates between 5th and 6th beta-sheets (green arrows) forming a ribcage-like structure supported by strong polar interactions (yellow interrupted lines). Model also predicts a zinc finger domain among Cys-72, Cys-77, His-58 and His-104 residues (orange).
In domesticated sorghum lack of first beta-sheet disrupts the integrity of the rest of the beta-sheets. There are a total of 17 polar interactions in wild sorghum molecular model. Among them 15 maintain the B-sheet orientation. Remaining two interactions are with WRKY domain and may be playing the central role in DNA binding.
Thanks to computers and intelligent programs we can visualize things that are beyond our perception. They are indeed “dream machines” that enable us to model and animate complex shapes and interactions. This is so powerful that we can even talk about disciplines such as molecular archeology as genetics and archeology begins to converge marvelously as we see here.