Question about the number of human genes that are projected into the chimp genome


(Jackson) #1

Hi, I’m new here.
From my understanding the people involved with sequencing the Human and Chimp Genomes also have something to do with this website.
I am struggling to understand some of the data I’ve read. It seems like Human genes have been directly inserted into the Chimp genome.
Particularly the protein coding regions. -
The genome was aligned to human GRCh37 using BLASTz in an eHive pipeline. These alignments were used to transfer human ensembl gene structures (Human Build 63) to chimpanzee…

Owing to the small number of proteins (some of which aligned in the same location) an additional layer of gene structures was added by projection of human genes. The high-quality annotation of the human genome and the high degree of similarity between the human and chimpanzee genomes enables us to identify genes in chimpanzee by transfer of human genes to the corresponding location in chimp…

https://www.ensembl.org/Pan_troglodytes/Info/Annotation

It seems very possible the over 90% of the protein coding genes in the Chimp Genome are actually human genes. Can this be correct?


(Steve Schaffner) #2

The description you quote is hardly the clearest bit of writing I’ve seen, but what it is describing is the process for identifying where genes are in the chimpanzee genome. Since most genes are in the same place in the human and chimpanzee genomes, and since human genes have been investigated more thoroughly, transferring the information about those genes to the database for the chimpanzee genome is an effective way to annotate the chimpanzee genes.


(Jackson) #3

That is kind of what I thought, but the more I read, the less clear this becomes.

In the Supplemental data it states
The Final Gene set -
820 Chimpanzee
5206 Human Ensembl
12720 Human Projections

Can they seriously be telling us that 90%+ of the chimp genes are actually either human or human projections?

My understanding is the protein coding genes are the hardest to sequence -
In 2004, the genome project reported that there were 341 gaps in the sequence. Most of the gaps — 250 — are in the main part of each chromosome, where genes make the proteins that life runs on. These gaps are tiny. Only a few gaps — 33 at last count — lie in or near each chromosome’s centromere (where the two parts of a chromosome connect) and telomeres (the caps at the end of chromosomes), but these 33 are 10 times as long in total as the 250 gaps.

So if the human protein coding genes aren’t really sequenced how can the chimp’s be?


(Steve Schaffner) #4

Human projections? Sure. Why not? The sequence of the genes is nearly identical. I don’t know exactly what annotations they were transferring. Locations of exons, splice sites, coding region. Why shouldn’t those annotations be transferred?

No, they’re the easiest to sequence. They are the least likely to have repetitive sequence.[quote=“toocoolblue, post:3, topic:37047”]
So if the human protein coding genes aren’t really sequenced how can the chimp’s be?
[/quote]
There may still be a few missing protein coding genes (probably not many, because genes have been sequenced even though they’re surrounded by repetitive sequence). They’ll also be missing from the chimpanzee genome, most likely – and others, too, since the human sequence is much more complete than the chimp. And of course, there’s really no such thing as “the human genome”. There are billions of slightly different human genomes, and a lot more than that if you include somatic mutations. What’s your point?


(Jackson) #5

My point is to learn something.

When I am told that human and chimp DNA is 99% similar, and then I find out that this is statistic is based on only comparing 2.4 billion base pairs from each species.

I begun to ask some questions. Such as, why do you exclude 700 million human bases and 900 million chimp bases from the study?

The answers I found were troubling. -
We created two distinct assemblies, one called the modified de novo assembly (MDN) and the other called the validated chimpanzee-on-human assembly (VCH). We then performed a partial merger to obtain the final assembly described by the Consortium.

What kind of science creates a “chimpanzee-on-human assembly” and then merges that to obtain the final chimp assembly? How can anything human be used to construct the chimp genome in a fair comparison?

Everywhere I look, I see evidence that the consortium decided that the human genome was exactly identical to the chimp genome - before they ever conducted a single test - and then they let that thought warp every decision they made through out the rest of the project.

I hope this isn’t the case, so I am looking for explanations to what seems like the most outrageous case of scientific fraud in the history of science.


(Steve Schaffner) #6

I know of no study that excluded hundreds of millions of bases from a comparison of the human and chimpanzee genomes. The study I’m familiar with compared all the bases that they could possibly compare. How would you propose to compare bases that haven’t been sequenced, or that can’t be assembled because they are too repetitive?

The kind of science that’s interested in getting the best result with the available data.
In case you hadn’t noticed two assemblies were done, one reliant on the human genome and one (the PCAP assembly) not reliant. The former was covered much more of the genome and had fewer likely errors. Had they chosen to use the PCAP assembly, would you be complaining about the additional hundreds of millions of bases that were excluded from the comparison? [quote=“toocoolblue, post:5, topic:37047”]
How can anything human be used to construct the chimp genome in a fair comparison?
[/quote]
What do you mean, “fair comparison”? The large-scale structure of the human genome really is very similar to that of the chimpanzee genome. Using one to guide the assembly of the other does nothing at all to preclude finding the many millions of differences between the two, including insertions, deletions and rearrangements.

How could the consortium have been simultaneously assuming the two were identical and also looking for (and finding) tens of millions of differences between them? Have you considered the possibility that they knew what they were doing?

Why on earth would anyone perpetrate such a fraud? What would be the point? In any case, if you’re really concerned use the chimpanzee assembly 2.1; it’s a PCAP-based assembly, with additional sequencing that’s been added since the first assembly was made.


(Jackson) #7

PCAP Assembly (Huang 2003)
However, human sequence and several finished chimpanzee BACs were used in post-assembly evaluation of potential local and global misjoins. A local misjoin involves erroneously ordered or oriented contigs from a limited region of the genome. In a global misjoin, contigs from disparate regions of the genome have been spuriously linked. We used an iterative strategy to reduce the numbers of both local and global misjoins. In each iteration, a chimpanzee assembly was first produced. Global and local misjoins in the assembly were then found by comparison with human genome sequence, as well as finished chimpanzee BAC clones. Appropriate modifications were made to PCAP after examining the nature of these errors, as described below.

Again and again and again the Chimp genome is modified to conform to the Human genome.

Really…

The draft genome assembly—generated from ~3.6-fold sequence redundancy of the autosomes and ~1.8-fold redundancy of both sex chromosomes—covers ~94% of the chimpanzee genome with >98% of the sequence in high-quality bases

Let’s do some math…What is 94% of 3.3 billion? Is it 2.4 billion?

Because that is all the Consortium compared -

They had sequenced significantly more of both the human and the chimp genomes then they compared. They specifically excluded the largest mismatched sections.just because they were different.

“Best reciprocal nucleotide-level alignments of the chimpanzee and human genomes cover ~2.4 gigabases (Gb) of high-quality sequence”.24 At this time, the human euchromatic assembly was estimated to be 99% complete at 2.85 Gb and had an error rate of 1 in 100,000 bases

It took 13 years to sequence the human genome, but only 2 years to sequence the chimp.Why? Because it wasn’t produced.to be accurate, It was produced to be a copy of the human genome.

They cherry picked the data and manipulated it to produce the answer they wanted to hear.

Such as only using one cherry picked chimp to make up almost the entire chimp genome… and then killing that chimp so further tests can’t be conducted. Chimp aren’t even genetically similar to each other much less humans. In Africa, Chimps have shown more genetic diversity in 1 square mile area than in the entire human race.

Telling people that Humans and Chimps are 99% genetically similar, while not telling them that you are ignoring 25% of the genomes, (the vast majority of which have been sequenced.) but are ignored because they DO NOT align with each other… is disgraceful.

So yes… “Have you considered the possibility that they knew what they were doing?”

I have considered the possibility, and I have no doubt they knew the fraud they were committing. And shame on you for trying to defend them.

If you know this much about the project, then you exactly why they excluded the mismatched parts of the genomes.


#8

What? 


#9

My guess would be the technology is much better now. Or at least that is what I have heard.

They cherry picked a chimp before the sequencing because they knew what the sequencing would be? Where is my tin foil hat. Stored tissue samples can be used for years, Ever hear of DNA tests run on evidence that was collected 10 years ago?


(Jackson) #10

According to Minute Earth -

A whopping 1.3 billion letters of sequenced, comparable DNA was excluded from the Genome comparison simply because it is different.

As far as the Chimp thing goes… Craig Venter said the same thing as me…
But what does he know?

Clint was the living reference point for millions of dollars’ worth of genetic code. One of the reasons he was chosen was his youth and clean bill of health: if researchers needed to take more tissue samples to validate the DNA sequence, he would be around to provide them. And as insights into the function of his genes emerged, they would be able to examine his morphology, behaviour and physiology.

But Clint has been put down aged just 24, New Scientist has learned. The Yerkes National Primate Research Center in Atlanta, Georgia, where Clint was kept, will not say what disease he was suffering from.
https://www.newscientist.com/article/dn6843-genome-project-chimp-dies-unexpectedly/


(Jackson) #11

Just one group of chimpanzees can have more genetic diversity than all 6 billion humans on the planet
http://homepages.rpi.edu/~eglash/eglash.dir/ethnic.dir/race/chimps/chimps.htm


(Jackson) #12

[content removed by moderator] [Do you] think that they randomly selected one single chimp to represent the entire species?
[Do you] think that Chimps who live to be 60+ years old, in captivity and were specifically tested to be healthy enough for further testing just die of unknown causes?

And for the record, the preservative methods used by the Genome Consortium conveniently failed.Their results can’t be questioned.


(Steve Schaffner) #13

You seem to be confused here. So far, you’ve pointed to gene annotations taken from the human genome; they involved no modifications to the chimp genome. Then you pointed to the human-based assembly, which did indeed depend (fairly modestly) on the human genome. Now you’re pointing to an alternative to that assembly, that depended hardly at all on the human genome. As far as I know, the subsequent iteration didn’t depend at all on the human genome. So as you look at less and less dependence on the human genome, you become more and more outraged.

I have to say, for someone who claims to be here to learn, you sure do come across as having an axe to grind. [quote=“toocoolblue, post:7, topic:37047”]
Really…

The draft genome assembly—generated from ~3.6-fold sequence redundancy of the autosomes and ~1.8-fold redundancy of both sex chromosomes—covers ~94% of the chimpanzee genome with >98% of the sequence in high-quality bases

Let’s do some math…What is 94% of 3.3 billion? Is it 2.4 billion?
[/quote]
No, it’s 2.7 billion. It’s talking about 94% of the euchromatic genome, which is (as you quote later) 2.85 billion base pairs long. But you don’t have to do any calculations: just look at Table 1. 2.7 billion bases of chimp sequence had consensus bases called and assembled. If you read the first Supplemental Note, you will find more details. 2.73 Gb of chimp sequence could be assembled into scaffolds. (And if it isn’t assembled, it might as well not exist.) Of that, 2.7 Gb had significant alignment to the human genome. After overlapping scaffolds were removed, there were 2.41 Gb of chimp sequence. Of that, 280 Mb aligned to parts of the human genome that weren’t assembled into chromosomes (because no one knew where they went), and a total of 91 Mb didn’t have an assigned location in the human genome. Given the quality of the chimpanzee genome (and to a lesser extent the human genome), most of that probably represents badly assembled sequence, but one never knows.

Mostly because the technology had gotten a lot better. But also because, no, it wasn’t produced to be as accurate. You do realize that the Human Genome Project cost something like 3 billion dollars, right? Do you really think there was a spare billion or two dollars lying around to sequence the chimpanzee genome to the same standard? [quote=“toocoolblue, post:7, topic:37047”]
It was produced to be a copy of the human genome.

They cherry picked the data and manipulated it to produce the answer they wanted to hear.
[/quote]
No, it was produced to be the best genome that could be produced for the available funds. And what answer that they wanted to hear? The whole point of the project – which involved a heck of a lot of work by a lot of people – was to learn what the chimp genome was like. [quote=“toocoolblue, post:7, topic:37047”]
Such as only using one cherry picked chimp to make up almost the entire chimp genome
[/quote]
Your accusations are going from the technical to the absurd. “Cherry-picked chimp”? What the heck could that possibly mean? Do you think they sequenced dozens of chimps and picked the one whose sequence they liked the best? [quote=“toocoolblue, post:7, topic:37047”]
and then killing that chimp so further tests can’t be conducted.
[/quote]
Oh my God! They murdered Clint! The bastards! [quote=“toocoolblue, post:7, topic:37047”]
Chimp aren’t even genetically similar to each other much less humans. In Africa, Chimps have shown more genetic diversity in 1 square mile area than in the entire human race.
[/quote]
Chimps have about twice the genetic diversity of humans. [quote=“toocoolblue, post:7, topic:37047”]
Telling people that Humans and Chimps are 99% genetically similar, while not telling them that you are ignoring 25% of the genomes, (the vast majority of which have been sequenced.) but are ignored because they DO NOT align with each other… is disgraceful.
[/quote]
Yeah. It’s also false. [quote=“toocoolblue, post:7, topic:37047”]
I have considered the possibility, and I have no doubt they knew the fraud they were committing. And shame on you for trying to defend them.
[/quote]
It’s much worse than that: I’m one of them. Just what mysterious conclusion was it you think we wanted to come to, and why would we go to so much trouble and expense to reach it? You surely don’t think we were doing it to fool creationists, do you? Because we weren’t thinking – or talking – about convincing creationists, or of proving to the public that humans and chimpanzees were related. Not at all. Ever. It’s hard to convey just how little working geneticists care about creationists. We sequenced the genome to use it. That’s the only reason we would have bothered.


(Stephen Matheson) #14

Are you serious!?!? This is nowhere NEAR the most outrageous case of scientific fraud in the history of science. Surely you know that all 6 of the moon landings were faked, on sound stages and outdoor sets near where I grew up in Arizona. They got Stanley Kubrick to help. Despite all the evidence of fraud, billions of people still believe that humans landed on the moon and even drove go-carts around on it. The scientists are inexcusably complicit—I think something like 99.666% of them claim that the landings were real. What kind of science creates a “moon landing” and then merges the fake pictures from Flagstaff, Arizona with real images of the actual moon?

Next are you going to tell me that Hoover Dam was built to make a big lake in Arizona, and not to hide a gigantic extraterrestrial robot kept dormant by continuous streams of liquid nitrogen? Or that Mount Rushmore is “art” and not a subterranean storage depot for the riches of an extinct South American civilization? Please, at least tell me that you know that Elvis is alive on Easter Island, hunting lemmings with JFK.

Genome annotation is so nerdy and boring. I think you should stop scouring the internet for ATGGGCCA and start asking whether the spaceship concealed inside the Great Pyramid (that’s real science, dude!) was really unknown until just this week. No way.


#15

That’s nice. But you aren’t defending what you actually wrote, which is the following:

“Chimp aren’t even genetically similar to each other much less humans.”


#16

Hey there, evil atheist scientist. Pyramid Christians are a thing, I tell you. It’s sort of a New Age/Christian syncretism. I had a conversation with one once. He believed that the Great Pyramid was built with such amazing, unique technology that the other pyramids don’t even compare. And that all this fantastic technical knowledge was lost in the flood. So suck it up, buttercup!


#17

Actually, they held open auditions. I read about it in Variety.

https://tse2.mm.bing.net/th?id=OIP.0WpZDcEYkszrYCjims_4FAEsC-&w=273&h=171&c=7&qlt=90&o=4&pid=1.7


(Steve Schaffner) #18

It’s also not true, by the way. The entire human population contains genetic variants at just about every site in the genome consistent with being alive. One group of chimps has far fewer variants.


(Peaceful Science) #19

Does this help?


#20

LOL. I don’t believe anything he says.