Nested Hierarchies


(Tim Wakeley) #1

I read Dennis’ info about nested hierarchies and the examples of the GULO gene and olfactory genes.
Please show examples of functional genes being added that show nested hierarchies. I think that would be a stronger case.

In the example of the GULO gene damage, was the entire Cytosine molecule removed, or was it damaged? Does the same damage appear in human, chimp, and orangutan?


(Dcscccc) #2

hi tim. the gulo example cant be an evidence for a commondescent. this is because it has been pseudogene in some species without a commondescent. for example: some scpecies of bats, fishes and mammals also get this pseudogene. but this happaned by convergent:

“The loss of activity of the gene for L-gulonolactone oxidase (GULO) has occurred separately in the history of several species. GULO activity has been lost in some species of bats, but others retain it.[4][5] The loss of this enzyme activity is responsible for the inability of guinea pigs to enzymatically synthesize vitamin C. Both these events happened independently of the loss in the haplorrhini suborder of primates, including humans.”

the guiea pig also share with humans a loss of some exons(1,5). so it even have the same mutations with humans gulo.


(Steve Schaffner) #3

In great apes and Old World monkeys, the gamma hemoglobin gene was duplicated and now forms two genes, both functional.


(Steve Schaffner) #4

Not really. Humans have lost exons 1, 2, 3, 5, 6, 8 and 11, compared to mouse. Exon 1 doesn’t really tell you very much – it only has three bases of coding sequence, and wouldn’t be the same in humans even if the gene were still functional. So humans have effectively lost 6 out of 11 exons, or more than half, while guinea pigs have lost 1 out of 11. It’s not at all surprising that the one lost by guinea pigs should also have been lost by humans, given how many they lost. In other words, that’s the kind of convergence we would expect to see by chance.

In contrast, chimpanzees have also lost exons 1, 2, 3, 5, 6, 8, 11. And so have macaques. And so have gorillas. In other words, all of the other higher primates have lost exactly the same exons as humans, which is not at all what you would expect by chance.


(Tim Wakeley) #5

Since the separation between mouse and human, have both lost approx the same total exons? I assume the mouse did not stop loosing exons.


(Dcscccc) #6

hi glipsnort.

you said that guinea pig lost only 1 exon. according to this paper he lost allmost 3 that human also lost:

“The GLO gene of anthropoid primates has lost seven of the twelve exons found in functional vertebrate GLO genes, whereas the guinea pig has lost its first and fifth exon as well as part of its sixth exon”

so this convergent cant not be by chance.


(Tim Wakeley) #7

When does loosing an exon become fatal to the animal? Have species specific exon taken the place of the ones lost?


(Steve Schaffner) #8

Mice have not lost any exons. If an animal relies on a gene, then a mutation that removes an exon is bad for it, and will not be passed on to later generations. That’s why there are so many more mutations apparent in the human GULO pseudogene: nothing stops mutations from accumulating.


(Steve Schaffner) #9

The birth of new exons


(Steve Schaffner) #10

Hi dcscccc,

As I mentioned, I was ignoring the first exon because it is almost entirely noncoding, and didn’t think it would be similar enough in humans even if our copy of the gene were intact. After thinking about it a little, I’ve decided that was probably wrong. So, counting just exons that have been completely lost, guinea pig lost 2/12 and humans lost 7/12. The probability that the two missing guinea pig exons would also be missing in humans is therefore (7/12) * (6/11) = 32%. (The probability that the first missing g. pig exon would be missing in human is 7/12, since there are 7 missing exons out of 12 possible. If the first one matches, the probability that the second missing g. pig exon will also be missing in human is 6/11, since one of the missing human ones has already been matched.) 32% is not at all unlikely by chance.

If you want to include partially missing exons, you have to include the fact that humans are missing half of exon 7, half of exon 9 and three-quarters of exon 12 (as far as I can tell from comparing the sequence, that is), leaving only 2/12 exons more or less intact. The probability that the missing or partially missing 3 guinea pig exons would also be missing or partially missing in humans is then (10/12) * (9/11) * (8/10) = 54%, i.e. it’s more likely than not.

So no, the missing guinea pig exons are not at all surprising by chance.


(Dcscccc) #11

ok glipsnort. lets continue. great, so the chance is 1\3 against the claim that this is the result of random mutations. but i think there is more to add. we need to combine this with the chance that the closest species to primate (that have a pseudo-gulo) is also the one that have the most similar exon loss. so if we know about 5 species that have a pseudogulo the chance is now about one in 1/3*1/5. or about 2%. its very unlikely from a chance prespective.


How does evolution rule out progressive creation?
(Steve Schaffner) #12

Sorry, but I don’t see what scenarios this calculation is supposed to distinguish between. One possibility is that shared exon loss in primates results from shared descent, while shared exon loss with guinea pigs is the result of chance. Under this scenario, the phylogenetic distance is irrelevant. What is the alternative that you’re proposing? What scenario would make shared exon loss between higher primates and guinea pigs more likely than under the chance hypothesis?


(Dcscccc) #13

what i suggest is that this loss between primates species isnt the result of a commondescent but a convergent loss. its likely that a similar genome will give us a similar exon loss.


(Steve Schaffner) #14

Okay, that makes some sense. It’s not really a plausible model, however. Mechanistically, what drives repeated loss of the same segments of chromosomes is the presence of nearly identical repeats. Researchers have looked for repeats to explain the loss of GULO exons in particular lineages and haven’t found them. More to the point, such repeats would not be shared across species as different as humans and monkeys, much less with guinea pigs; the genomes are just too different at the sequence level.

Basically, you have to postulate an unknown mechanism that is 100% effective at removing a particular set of exons from all great apes, lesser apes and Old World monkeys. Maybe New World monkeys too – I haven’t checked to see whether they’re missing all of the same exons. That mechanism is 0% effective at removing those exons from the lemurs and other non-monkey primates, but works partially in guinea pigs. That does not sound like any mutational mechanism that occurs in nature.

Your proposal is much less parsimonious than the conventional one. You have to have 100+ separate, identical sets of at least three deletions, to account for GULO’s loss in higher primates. The alternative is one set of (at least) three deletions, that took out the gene in primates, and one or two deletions in guinea pig that happened to overlap with one of the primate deletions.


(Dcscccc) #15

its actually very simple: species that have a functional gulo need it. so we should not expect to see an exon loss in their gulo. only the species with pseudogulo count. so if we see that allmost 3 exon can be loss without a commondescent, it also possible that 6 exon in different species can be loss without a commondescent.


(Steve Schaffner) #16

Humans could certainly use a functional GULO gene – millions have died from scurvy. And you think it’s just a coincidence that every single ape and OWM species doesn’t need GULO and happens to have lost exactly the same exons (not to mention the other missense and nonsense mutations that are distributed across the primate tree), while every single lower primate species does need GULO? That really strikes you as likely?


(Dcscccc) #17

“Humans could certainly use a functional GULO gene -”-

true. but when he lost it he lost it. so after the loss it have lost its exons.

" And you think it’s just a coincidence that every single ape and OWM species doesn’t need GULO and happens to have lost exactly the same exons"-

i can ask you the same: is it just coincidence that cavia and human (and other some species) lost their gulo and even with the same exon?

" while every single lower primate species does need GULO? "-

its more impresive to me that some primate have a functional gulo, when cavia and human share not just pseudogulo but also the same exon loss. from phylogenetic prespective (that only base on this single gene)) it can mean that human is closer to cavia then same primates.(yes. i know that its not true and we most check also the indels and so on). i speak in general term.


(system) #18

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