Molecular genetics (sapolsky human behavioural biology) Flashcards
For our purposes, what is the central dogma of life?
- Information flows from a unique DNA sequence (a gene) to an RNA sequence to an amino acid sequence.
- By extension, one gene specifies one protein which has one shape and therefore one function
And what is the main challenge to the central dogma in this course?
- That one stretch of DNA can actually lead to many different proteins (through alternative
splicing) - (also retrotranscription in viruses from RNA –> DNA)
- (also one protein can take on multiple conformations and serve different functions)
What are the molecular bases for the three tenets of evolution by natural selection?
- Traits are heritable: you get your genes from your parents, and them from their parents, and so on.
- Variation: different alleles (versions of genes) code for slightly different proteins that serve the same function.
- Differential fitness: those different versions might do their protein job slightly better or worse, depending on the
environment in which they’re working
What are the three types of mutations in classical genetics?
- A point mutation when a single nucleotide is copied differently (incorrectly) between a mother cell and a daughter cell.
a. Can be a neutral mutation thanks to the redundancy of the codons. That is, multiple sets of 3 DNA bases will code for the same amino acid. So if the point mutation changes from one codon into a different but reduntant codon, it’s a neutral/silent mutation. - An insertion mutation leading to a frameshift.
- A deletion mutation leading to a frameshift. Deletions can also be of entire genes.
What do we mean by microevolutionary vs. macroevolutionary change?
- Micro: a change in a single protein that affects a single protein and the downstream effects of having a differently shaped protein.
- Macro: a change in something (promoter, transcription factor, splicing enzyme, transposase, etc) that produces far-reaching changes in the way many proteins are made or when they are expressed.
Four examples of a microevolutionary change having a big impact on behavior?
- Phenylketonuria (PKU)
- And two examples related to testosterone?
a. If your T receptors are mutated and don’t function, you are genetically XY male but have female appearance because your body doesn’t respond to the presence of T. This is testicular feminization syndrome.
b. Enzyme that makes T is mutated in early life, but doesn’t hold back T production at puberty in populations in New Guinea and Dominican republic. Guevedoces: what are thought to be “girls” (but are actually XY) develop male secondary sexual characteristics around puberty when T kicks in. - And an example related to anxiety?
a. The benzodiazepine receptors come in different versions based on subtle mutations. b. The better the receptor binds BDZs, the less anxious the individual will be. If they’re
very poor BDZ binders, the individual will have an anxiety disorder.
How can micro mutations tell you about evolutionary ancestry trees?
- We share “the gene” for many proteins with distantly related species (a significant percentage of our genes are shared with bananas, for example).
- But as species evolve and diverge, differences accumulate in our genes so that the proteins of very distantly related species have many differences between them while the same proteins in very closely-related species have very few differences between them.
How do you know if a protein has undergone positive selection or negative selection?
- Take a protein product that is shared between species, like a serotonin receptor shared between dogs and humans.
- Look at the DNA sequence that codes for that protein. Just by random chance we expect, say, 1/3 of the mutations (differences) between those two DNA stretches to actually code for a different AA (amino acids), resulting in a slightly different protein.
- However, if 3/4 of the mutations coded for different AAs, this gene has undergone positive selection and the differences that have accumulated were the result of selective forces over time selecting for a new and better version of that gene.
- If say 1/8 of the mutations coded for different AAs (that is, more of the mutations were neutral than you’d expect by chance), then that gene has undergone negative selection/stabilizing selection, meaning that it is very conserved among species because slight changes have been selected against.
If that’s still confusing, here’s another explanation from last year: You start off with a gene in an organism at time T1.
After a long evolutionary time period during which the gene has undergone numerous mutations, you come back and re-examine the gene, which is no longer identical to its original form.
You’re comparing the newer version of the gene at time T2 to the original gene at time T1 and looking at the mutations that have happened.
Based on the type of mutations (silent/neutral or consequential) that you see, you can know whether this gene has faced selective pressures or not, and if so, what type of selective pressure.
If nothing interesting has happened and those genes have not undergone any particular selection pressures, you’d expect 1/3 of the mutations to be consequential (due to the mathematics of the DNA-amino acid link).
But if significantly more than 1/3 (like 90%) of the mutations are consequential, the gene has undergone positive selection because having so many more consequential mutations (ones that actually make a difference in the protein formed) than would be expected by chance means that, in order for this gene to have evolved this way and exist in its present form, that large number of consequential mutations must have been selected for.
And if significantly fewer than 1/3 (like 5%) of the mutations are consequential, the gene has undergone stabilizing/negative selection (pressures to keep the gene exactly how it functioned originally). This is because when consequential mutations happened along the line from T1 to T2, those changes were selected against and the original genetic sequence is highly conserved.
What is the 95% of DNA that doesn’t code for proteins?
Promoters, repressors, and “junk DNA” which we don’t know much about
The longer the genome in a species, the greater percentage of genes tat code for Transcription factors
How do you know when to express certain genes?
Can be answered at many levels.
a. When the transcription factor (TF) binds to the promoter
b. When the intra-cellular environment signals transcription via TFs
c. When the inter-cellular environment signals transcription, e.g. via testosterone
d. When the inter-organismal environment signals transcription, e.g. a mother smelling
her newborn.
How do you know when to express certain genes?Overall, this is the concept of if-then clauses. (example)
Example: if you smell your newborn baby, then express genes related to nursing.
What’s 1 molecular mechanism and 1 example of epigenetic regulation?
- Chromatin packing patterns can be set for life.
- Examples include
a. Metabolic programming during the Dutch Hunger Winter
b. Stress reactivity in rats as a function of licking and grooming from the mother
What do transposons do and where do we see them play out in nature?
- Transposons are mobile bits of DNA clipped by transposases and inserted into random parts of the genome
- Originally found by Barbara McClintock in corn. Often found in plants as a stress response to come up with a novel solution under dire circumstances that plants can’t run away from.
- Also seen in neuronal wiring of mammalian brains. Significance: the organ having MOST to do with behavior is LEAST deterministically goverend by one set of genes. A lot of noise in the system and less of a role for a deterministic view of genes.
- Also seen in parasites like the trypanosome worm which uses transposons to reshuffle its surface signal proteins to evade immune defenses.
- Also seen in the immune system of mammals.
What’s the basic idea of Punctuated Equilibrium (PE) and what’s the evidence for it? How do
gradualists respond to those claims?
- PE is a model that explains evolution. The idea is that there are long periods of stasis (the equilibrium part) in which nothing exciting really changes and then periods of saltation (the punctuated part).
- Paleontological evidence: we see in the fossil record what looks like saltatory change and periods of equilibrium
a. Gradualist (“creeps”, as opposed to PE “jerks”) say the fossil record is incomplete and maybe it’s gradualist if we had more data.
b. Gradualists also say that “sudden” change for PE folks is plenty of time for sociobiologists to examine evolution of behavior in what they’d call a gradual manner.
c. Gradualists also say that PE folks are only looking at morphology or the way things are shaped. You get very different behaviors based on neurons and brains, and you can’t directly examine those with paleontological evidence.
d. Gradualists in the old days also demanded to see molecular mechanisms for these changes. See below for response.
What’s the molecular mechanism of Punctuated equilibrium changes?
- Mutations in the regulatory regions of genes. We call these mutations macroevolutionary.
a. Theseinclude:promoters,repressors,TFs,splicesomes,andtransposases. Transposon action itself (even when not mutated) can change entire if-then sequences. - And multiple genes can be regulated by one TF or one promoter
- And any given single gene probably responds to multiple TFs and promoters.
So we have networks of genes and when you disrupt the controllers of those networks,
their regulators, you can produce radically new if-then clauses. So a new environmental situation can trigger an existing pattern, OR the same environmental situation can trigger a new pattern if you have just small mutations in any of these regulatory sequences.
