Chimpanzee Contigs and the Human Genome: 84% Similar?

(Glenn Williamson) #21

Okay, video is up on my channel!

The reason he gets 84% is pretty embarrassing: he gives the percentage similarity of a 1,000 bp sequence the same WEIGHT as the percentage similarity of a 2,000,000 bp sequence.


(S. Joshua Swamidass) #22

@roohif, can you explain it a bit here in text?

Excellent video by the way. It seems that Tomkins really did make an error.

(Ashwin S) #23

So what is the bottom line?
98% similarity? or 96% similarity?

How does a 2% difference account for the difference between chimps and human beings, especially considering most of the differences in the genome should be due to neutral mutations (i.e they don’t effect fitness).
Shouldn’t this be a problem?
On top of that, there is the claim that humans share 97.5 % of our “working” DNA with mice.

Does counting bases and measuring differences really explain differences in the phenotype?

(Blogging Graduate Student) #24

As far we can tell, the “true” identity is between 95% and 98%, depending on how you do the comparison.

Yes, most of the differences will be neutral between humans and chimps. I don’t see how that’s a problem.
Merely counting bases doesn’t explain phenotypic differences, of course. Investigating those base differences and seeing how they affect phenotype is what explains phenotypic differences.

That figure of 97.5% “working DNA” is based on the number of genes mice have on chromosome 16 compared to the human genome. In other words, 97.5% of mouse genes on chromosome 16 have a corresponding gene in the human genome. This number was estimated in 2002, and doesn’t even include the sequence identiy, just the presence/absence of a few hundred genes. I’m sure you can find better and more meaningful figures in 2018.

(Ashwin S) #25

If most of the differences are neutral, then the the major part of the 2- 5% difference will be trivial(i.e not contributing in any major way to the organism). Which means the actually important parts of the genome that causes the change would be very less (perhaps less than 1%?)
To me, this seems to say that the major changes are caused by the way genes are regulated as opposed to new genes perse.
If this is so, difference in bases does not explain much.

(Blogging Graduate Student) #26

Of course the major changes are mostly the result of changes in gene regulation rather than changes to the genes themselves. That’s been conventional wisdom for decades. You seem to be implying that evolutionary changes in regulation doesn’t involve base changes, which is completely wrong.

(Steve Schaffner) #27

As @evograd points out, what determines how genes are regulated is DNA. Most of the relevant DNA differences between humans and chimpanzees are in regulatory DNA.

(Ashwin S) #28

I am implying nothing of the sort. I am implying that most base changes must be neutral (can you share a percentage?, shall we say about 90%? )
If the difference between humans and chimps is 2%, then, only about 0.2% will be non neutral assuming mutations are random with respect to fitness.

So the obvious question is whether such a small tweak is enough to get a human being from a chimp? or is something more going on?

(Blogging Graduate Student) #29

Ok, I misunderstood you then.

0.2% doesn’t sound like much, but put another way, that’s 6 million base changes. That can change a lot of regulatory networks. Then there’s all the rearrangements to think about as well. What “more” are you hinting at could be going on?

(Steve Schaffner) #30

Probably less than that. I think it unlikely that 10% of differences between the species had any effect on phenotype.

Short answer: yes, it’s more than enough. It’s enough to change lots of genes and change the regulation of every gene many times over.

(Ashwin S) #31

What exactly do you mean by the “rearrangements”?

This is the part i don’t get. How do you know this.
Its not like scientist have figured out what every gene does right.
As far as i understand, a lot of the details of how genes/gene regulaton leads to phenotypes is also unknown.

(Ashwin S) #32

Ya it probably is. I did not count deleterious mutations that get selected out either. How about this, 10 Neutral mutations, 99 % deleterous mutations, So for 2% change we have -
2X0.1X0.01 = 0.002% ; i.e about 60000 beneficial base changes. (edit corrected the calculation)
Would this be more realistic?
Edit : or do deleterous mutation not get counted, because tehy dont get fixed?

(Blogging Graduate Student) #33

Physical shuffling of genes, regulatory elements, etc within and between chromosomes.

We know enough about developmental biology to know that comparitively small changes in regulation can cause large changes in morphology. Fundamentally, humans and chimps are next to identical, so the vast majority of development wouldn’t have to change.

(Ashwin S) #34

These will not be counted in the difference measured ?

Ya, but most changes that effect regulation would be deleterous or neutral. So you would need a lot of right changes at the right time…
I guess that is contingency?

(Blogging Graduate Student) #35

Not in the percentage identity figures. Why would they?

That’s true for all mutations. You’re changing the subject from “do the DNA differences cause the phenotypic differences?” to “how did the DNA differences come to be?”

(Ashwin S) #36

I asked to get clarity. So, Would it be correct to say the percentage identity figures do not represent identity in function?
Say out of the 96% or 98% identical genome, a particular percentage can cause difference in phenotypes too?

I asked the question for clarity. As to DNA differences causing differences in phenotypes, dont organisms with the same genome also display different phenotypes? For example bees, butterfies etc. I was wondering whether something along those lines is going on.
Afterall the DNA difference between a butterfly and a caterpillar is Zero isn’t it?
Perhaps the “rearrangements” are more significant than actual base changes.

(Blogging Graduate Student) #37

Not sure what you’re asking here.

Yes, obviously external influences can differentiate individuals in populations. Organisms are quite plastic to their environment, to an extent. This is unlikely to contribute much to the evolution of divergent species though. Or are you suggesting that if a chimp embryo was successfully implanted into a human woman’s womb, grown to term, born, and raised among humans it would be significantly more “human-like” in terms of morphology, brain activity, etc?

The DNA difference between me as a baby and me as an adult is zero - that’s not at all analagous to divergent species.

(Ashwin S) #38

Can rearrangements lead to difference in phenotypes?

What does this have to do with honeybees and butterflies?
I am suggesting that the same genotype can produce different phenotypes.

Did you grow wings as an adult? of develop a new body plan?

(Blogging Graduate Student) #39

Of course, the spatial arrangement of things like enhancers is very important to function and therefore phenotype.

And no one would disagree with you there. My point is that those kinds of plastic responses are unlikely to contribute much to the human-chimp phenotypic differences.

Irrelevant. Both morphologies are still “present” in the DNA. Again, take this to its logical conclusion: are you suggesting that the DNA differences between humans and chimps don’t contribute to morphology, and that it’s all environmental factors that cause the observed phenotypic differences?

(Ashwin S) #40

So to summarise- out of 96-98% identical genome, a percentage contributes to phenotypic differences.
Out of the remaining 2-4% differences also, a percentage contributes to phenotypic differences.
In such cases, whats the point of looking at similarity at the nucleotide base level? It doesnt have much significance with respect to difference in phenotypes.

Thats not the logical conclusion IMO. The logical conclusion is that gene regulation can create a lot of phenotypic difference without change brought about by mutations.
In these examples environmental factors are not the cause for change in phenotypes. They are best pre-programmed specific triggers.