With so much variation, how can we make sense of it all?

The field of Evolutionary Genetics focuses on the interplay between genetic events, speciation, and phenotypic diversity. A noticeable part of genetics that has been seen to vary between species is gene expression. Despite this common trend, little research has been performed to assess the extent to which transcription factor (TF) binding differs among individuals of the same species and closely related species, as well as the overarching connection between TF binding and genetic variability. In order to figure out some of the mystery, Maya Kasowski et al. decided to look at the variation in TF binding among humans.

The researchers decided to use 10 individuals (5 of European ancestry, 2 of eastern Asian ancestry, and 3 of Nigerian ancestry) with extensive genetic data already existing for them, as well as one chimpanzee as a point of comparison because of how closely related they are to humans. Once they picked their people, they used chromatin immunoprecipitation plus sequencing (ChIP-seq: For a quick reminder check this out! http://en.wikipedia.org/wiki/Chromatin_immunoprecipitation ) to figure out the binding sites of two TF, RNA polymerase II (Pol II) and nuclear factor kB (NFkB). This two transcription factors were not picked randomly of course! Pol II catalyzes reactions that make the precursors of mRNA, snRNA, and microRNA while NFkB is a key regulator of immune responses as it acts as the last component that actually binds to the DNA to start transcription. As you can see, these factors are very important, and what’s more is that their different binding regions have links to many high interest diseases. For instance, type I diabetes, chronic lymphatic leukemia, and schizophrenia relate to Pol II genes while asthma, Crohn’s disease, and rheumatoid arthritis relate to NFkB.

Overall, the results they found were that differences of 7.5% and 25% exist in TF binding for NfkB and PolII respectively between the individuals they studied, but the estimated value for sequence variation in coding sequences is only 0.025% between humans. Basically, what they found was that there was a very strong role in binding variation in human diversity. When I first read the article, 7.5% and 25% did not seem like large enough numbers, but compared to 0.025% this is a very significant difference that deserves further research. An interesting finding of theirs is that these differences were more likely to be found in variable regions of the genome, such as those involved in immune response. This makes sense because the individuals that had more variability in their immune responses would survive preferentially due to their increased ability to adapt to novel diseases or viruses. Further research after this study could expand upon their studies. How can they apply their findings to human medicine once they recognized the disease loci? Will they now be able to even more accurately explain speciation events and phenotypic diversity? I don’t know what will come of the further research, but the endless possibilities are sure to be central to evolutionary genetic research for years.

Kasowski, M. et al., 2001, Variation in Transcription Factor Binding Among Humans, Science, v. 328, p. 232.