Molecular Genetics II. 1h 14m Robert Sapolsky video.

Mutations in a splicing factor can lead to completely new proteins. Mutations in a promoter could change the transcription factor and lead to whole networks of new proteins. That is, mutations in the epigenetic infrastructure can lead to BIG evolutionary changes.

When comparing different species, the more genes the greater is the percentage that are transcription factors. Given a set of n genes, you need 2^n - 1 transcription factors to control every combination of them. A disproportionate share of the differences between the human and chimp genomes are genes that code for transcription factors. Microevolution is about the function of proteins; macroevolution is about which proteins and hence is far more consequential. Macroevolution is about new proteins, new networks, and new if-then clauses. E.g., compared to the chimp, the human immune system is better against tuberculosis but worse against malaria.

Barbara McClintock (1902-1992) was a distinguished plant geneticist developing pathbreaking new techniques in her early work. In 1944, she became the third woman elected to the National Academy of Sciences. But then she made a career ruining discovery: her data on maize implied that there are transposable genes or transposons (so-called "jumping genes"). After decades of reproach, the evidence that she was right finally led in 1983 to her becomming the only woman to receive an unshared Nobel prize in Physiology or Medicine. Plants have an inducible transposable genetic capability as part of their stress response. Animals and humans have a similar capability in their immune response with antibodies. In primates, neural progenitor cells, which make new neurons, have an inducible genetic shuffling. "The cells in your body that have the greatest to do with making you who you are are the least constrained by genetic determinism."

Copy number variants are where there are multiple copies of a gene. The copies could be backups or the effect may be proportional to the number of copies. This gives evolution the opportunity to "experiment" with copies of a gene to try out new things while having the original functionality persist.

Some examples. Vasopressin is a hormone that affects the social affiliative behavior of male voles (and possibly humans!). By controlling a promoter (gene therapy), a polygamous male can be made monogamous. Human males with one promoter are more likely to get divorced than other forms. What does that say about free will?

Dynorphin is a hormone neurotransmitter involved in pain perception. The number of copies of a promoter predicts how readily subjects became addicted to drugs.

Steroid hormones like estrogen, testosterone, and glucocorticoids have two parts which are coded on different exons: a hormone binding domain and a DNA binding domain. Hydrocortisone (aka cortisol), one of the glucocorticoids, is a stress hormone that suppresses the immune system. Progesterone could have evolved by replacing the hormone binding domain to suppress the immune system during pregnancy. Joe Thornton has shown that a lot of the steroid receptors were once duplicated genes.

But it is a long shot for any of these mutations to "get something interesting". So we get long periods of equilibrium with not much change happening. Stabilizing selection will weed out most changes. There can also be selective bottlenecks where only those with a particular trait make it. This happened with Cheetahs about 200 kya: all Cheetahs are so genetically similar that they can take tissue transplants with little risk of complications.

He closes with some evidence for both macro and micro changes in genes that have been noticed. The fossil record shows some evidence for both macro- and micro-evolution. In Chicago over the past 100 years, we know the gene distributions are changing (someone preserved some 100 year old rats that have been compared to modern Chicago rats). The Pima Indians are split about half and half between Mexico and the US. There is a 96% rate of diabetes on the US side. Siberian silver foxes were domesticated for tameness in 35 generations. As a side effect, we get floppy ears, wagging tails, and piebald coloration. Both macro and micro mutation is happening.

5. Molecular Genetics II