Molecular Clock Puns

I've been reading about molecular clock studies, and they can be used to compare two different lineages and infer when did the common ancestor of those two different lineages live, based on the difference in non-coding regions of DNA (or regions with minimal negative selection). That inference is based on the premise that the mutation rates on a particular lineage remain relatively constant over time.

So for example when comparing wolves to lions, we can measure that difference in some homologous non-coding DNA region between them. And assuming the rate of mutation across their ancestry remains constant on those non-coding regions of DNA, the difference presented in those DNA regions would be proportional to the time that has passed since their divergence from a common ancestor.

And I've seen it works, when compared to radiometric analysis of fossils of possible candidates of common ancestors, the timing seems accurate. But how is that possible? I mean, how is it possible that the rate of mutation remains constant if different species present different generation times?

The way I see it, a population that gives birth to a new generation every 2 years should present more changes in their non-coding regions of DNA over time, than a population that gives birth to a new generation every 5 years. So how is it possible that the rate of mutation remains fairly constant over the linear metric of time considering every species presents different generation times? In the case of making that analysis with wolves and lions, when we go back in time through their ancestry, we have to pass through a lot of different ancestral extinct species before we reach the species that would be their common ancestor; but all those intermediate ancestral species, as they are extinct, they have uknown generation times to us, we don't know how often did they reproduce.

I've read on Wikipedia that molecular studies of the difference in the sequence of cytochrome c across species provides accurate relative times of divergence between species, even if we are comparing the difference between mammals and yeast, with the difference of frogs and yeast. Like both lineages (the one of some particular species of mammal, and the one of some species of frog) present a similar number of quantitative difference in their sequence of cytochrome c, implying that the time that has passed since the common ancestor of mammals and years lived, is the same time that has passed since the common ancestor

Title:

A new study suggests that a synthetic form of cordycepin, a compound found in a cheap medicinal fungus C.militaris, can reset the circadian clock at the cellular level for up to 12 hours.

> In mice, scientists found that synthetic cordycepin drastically helped the animals adjust to time change. Normally when mice are exposed to an 8 hour time change — imagine flying from New York to Abu Dhabi — it would take them 10 days to adjust. The mice on cordycepin took only four days. > > "We want to let people know that drastic and quick changes for our body clock are possible," Zhang says.

This works equally well for phase delay and phase advance:

> When they dosed mice with either 15mg/kg or 45 mg/kg of the synthetic cordycepin, the mice were able to more easily able to adjust when they were forced to live in a "time zone" 8 hours earlier than what they were used to, as compared to mice who did not receive the compound. That same pattern held when the mice were put in a time zone 8 hours behind their own (imagine flying from New York to Baker Island, an uninhabited island about halfway between Hawaii and Australia). "In both cases, our drug administration shortened the adaptation time to at least one half," says Zhang.

How it works?

> The team found the synthetic cordycepin can bind to an enzyme called RUVBL2, and influence transcription of clock genes. These are genes when are turned "on" and "off" as the body goes through our 24-hour cycles. > > RUVBL2, importantly, was abundant in areas of the mouse brain like the suprachiasmatic nucleus of the hypothalamus. This is the light-sensitive area of the brain that is the master controller of our circadian rhythm. > > Cordycepin binds to RUVBL2, which creates a cascade of changes. First, a crucial protein is forced to leave chromatin, a structure that condenses DNA into packages (like a .zip does for images). Once that protein leaves, other genes related to the circadian rhythm, called E-box genes, are transcribed freely. > > Cordycepin can be thought of as a key that "unlocks" the ability to transcribe those genes. Once that happens, a new oscillation (or a cycle of 24 hours) begins. The clock is reset. > > Overall, Zhang theorizes that this "magic drug can change the clock phase up to 12 hours."

Links/references: https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aba0769 and https://www.inverse.com/mind-body/cure-for-jetlag-fungus-compound

Keep i

Hi I'm a little confused about the concept of the molecular clock. So I understand that we can use the fairly constant rate of molecular changes over time to determine the time of divergence and the relatedness of two species. How does this constant rate of molecular changes relate to macroevolution? Which depends on many factors such as environmental selective pressures? And since the rate of molecular changes is dependent on time, how does the environment factor into this at all?

For context, I'm a student and we're doing a lab about the molecular clock. We've constructed the scatter plot to show the constant rate of accumulation in changes of the hemoglobin amino acid sequence of different primate species. But there's a question about the ancestral ring-tailed lemur and its native environment (Madagascar), and how the environmental restrictions influences the molecular differences of the lemur and other species? I'm confused because if the molecular differences is mainly dependent on time, I don't see how the environment would have anything to do with it?

Thanks in advance

Its also called gene clock

Please be very specific but understandable to laymen. I want to understand how divergence dates are estimated by use of a specific example.

>https://www.iflscience.com/plants-and-animals/ancestors-humans-and-chimps-may-have-begun-diverging-13-million-years-ago/
>
>[...] Earlier estimates suggested that the most recent common ancestor of humans and chimps lived around 6-7 million years ago; however, recent evidence has suggested that the mutation rates may have been vastly overestimated and that the most recent common ancestor (MRCA) in fact lived 12 million years ago. Now, a new study investigating the mutation rates of chimpanzees has provided further evidence to support this notion, suggesting that the MRCA lived around 13 million years ago. [...]

So, the "genetic origin" of sapiens would be roughly at 400 kya rather than 200, and the following splits about twice earlier than thought?

Big picture - how it helps track infectious disease outbreak for example to find origin ( since mutations are random )

Hi I'm a little confused about the concept of the molecular clock. So I understand that we can use the fairly constant rate of molecular changes over time to determine the time of divergence and the relatedness of two species. How does this constant rate of molecular changes relate to macroevolution? Which depends on many factors such as environmental selective pressures? And since the rate of molecular changes is dependent on time, how does the environment factor into this at all?

For context, I'm a student and we're doing a lab about the molecular clock. We've constructed the scatter plot to show the constant rate of accumulation in changes of the hemoglobin amino acid sequence of different primate species. But there's a question about the ancestral ring-tailed lemur and its native environment (Madagascar), and how the environmental restrictions influences the molecular differences of the lemur and other species? I'm confused because if the molecular differences is mainly dependent on time, I don't see how the environment would have anything to do with it?

Thanks in advance