What The Human Genome Project Discovered About Who We Are

in #biology7 years ago (edited)

270px-Human_outline.jpg

What an alien would see if he saw us in terms of chemical composition.
Source: Wikimedia Commons Contributors & Pixabay, modified

Curtain open

In the Star Trek episode Home Soil, an alien life-form made of crystal derides Captain Picard and his crew as "ugly bags of mostly water".

Chemistry has no opinion on the "ugly" part, but it does side with the alien when it comes to our body composition: we are on average 65% water; but if this is a concern to you, you can lower it to 45% by becoming very obese.[2]

Think of switching to another field that is less dismissive of your personhood? How about physics? Well, turns out, physics says you are mostly air, which is hardly an improvement. (To be exact, physics says you are mostly empty space, not air, but who wants to be exact when it ruins a joke.)

So next time someone calls you an airhead, and you think of firing back an insult, make sure he is actually being rude, rather than just being a physicist. (Though by all means, rudeness and being a physicist can be found in the same person, which makes matters even more confusing.)

But if chemistry says you're mostly wet, and physics says you're mostly hot air, what does biology say? If we're going to believe we're mostly not what we think we are, we need confirmations from at least 3 different hard sciences, or the transaction block isn't valid, so to speak.

Turns out, biology does confirm it: you are a mostly noncoding transposon. And no the last word doesn't refer to a new gender. (I have recently discovered I am cisgendered — also called a cis-sy — and while I'm adapting to this new gender identity, I see genders everywhere.)

If you don't know what a transposon is, this post is for you. Hopefully after reading it, you'll never look at yourself in the mirror in the same way ever again.

Our DNA is infected with parasites

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Unemployed graduate programmer. Will code for protein.
Source: Flickr

It was bound to come. But instead of doing a traditional treatment — of how the Genome Project came about, what the scientists did, what the quarrels were — I decided to just go through some of the main things the Genome Project discovered about us humans. Or rather, the things that it allowed us to discover, and that are still being discovered.

Number one, only about 8-15% of our genome codes for proteins. The rest of the genome is biologically non-functional (though this is debated, read here for instance), usually called non-coding DNA. The majority of this non-coding region is transposons, also called jumping genes, because they like to hop around the genome.

Given that most of the genome is non-coding, most of this hopping around is benign. Sometimes, however, these transposons land smack right in the middle of a coding gene, rendering it non-functional. More rarely, this might cause a beneficial mutation, which is why some consider transposons to be, in part, drivers of evolution. But mostly, they are selfish parasitic DNA.

Due to transposons having similar DNA sequences, they also initiate chromosomal recombination events (click to see a pic), which, again, is mostly harmful, but in some cases it will be beneficial.[4]

I could end this post here, declare that you are mostly air, or mostly non-coding, and be very well satisfied with my work. But since coding DNA does make up a (measly) 8-15% of the human genome, I guess for the sake of completeness I have to write a few words about it — about what you are mostly not. So let's talk about the coding part of your DNA — the part you mostly aren't. (I won't tire of repeating it.)

Remarkable lack of diversity

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Mostly white and phallic. Need more diversity.
Source: Pexels

You are not unique. Well, at least your code isn't. But why? There is no chemical reason why certain triplet letters should code for specific amino acids; and yet the genetic code is virtually identical, in bacteria, in archea, in eukaryotic cells.[4] If you and E. coli did not originate from the same source, we would expect different codes. A common code strongly implies a common origin.

But it goes beyond the genetic code, beyond the fact that AUG codes for the amino acid methionine. It also concerns the sequence in which all these letters are laid down. In fact, by studying the sequence, we can study how related we are to other organisms.

We are related to the chimps!

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This is the reason there are no chimp dentists. Too many dentist fingers went missing.
Source: Flickr

I know: isn't this old news? Didn't morphology already prove we are related to chimps? Well, bones and genes are different things. If a judge has video surveillance evidence that Jones committed a crime, will he reject DNA evidence that also show that Jones committed the crime, calling the DNA evidence redundant? No, he will accept the new evidence, that will now make the case even stronger, since video has nothing to do with DNA: two completely independent methodologies proving the same thing. It's referred to as consilience, and it's one of my favorite methods of proving...well, anything.

It's the same with the human genome: the idea that we are related to the chimps is old, but the method was brand new, and makes the conclusion that much more incontrovertible.

So let's say I have this crazy theory that apes are related to each other in certain ways, based on flimsy evidence like similarities between bones. And let's say I built this phylogenetic tree to depict these similarities.

Apeclade-.jpg

Source: Wikimedia Commons Contributors, modified

So let's say I've matched the genomes pretty nicely, but I see a few differences. The gibbon and orangutan have a T where the gorilla and chimpanzee have a C. Can I make a prediction about what letter the human will have in that position? Well, whatever mutation happened, apparently happened at branch 15. So it makes sense that the human would inherit the C, not the T. Could we check the genome and see that it's a T instead of the predicted C? Yes, because a mutation could happen again. But what are the chances that the mutation would again produce a T instead of any of the other letters, and that that mutation would have occurred in the time period we split from the chimps? That was a rhetorical question. Put the book back. But geneticists have mathematical ways of answering those questions. The chances are less than 1%. And then it's not just this one letter, it's millions of them.

So you have these amazing predictions, that the DNA sequence is able to bear out.

And what if a transposon jumped in the middle of a gene at position 15 there? And we see that transposon in the gorilla and the chimp? What are the chances it will be present in the human, at the same gene? Again, geneticists can calculate the probability of a transposon jumping back out given the timeframe, and it is small.[5]

Oh heck, let's throw in another (completely independent) prediction, just cos we feel like it. Mutations happen all the time. But not all of them are treated the same. 3-letter deletions are better than 1-letter deletions, because the code is read in threes, so 3-letter deletions restore the reading frame, whereas 1-letter deletions mess up the entire sequence. Silent mutations (changing a letter to another that still codes for the same amino acid) are better tolerated than missense (different amino acid) or nonsense (everything stops) mutations. So geneticists like to write software that contains all these rules, and makes predictions, and see if they pan out. Here is an example of such a software that pans out 84% of the time.

This isn't the only thing done by software. I hope it's unnecessary to state that phylogenetic trees are not created by hand. There are computer programs that analyze sequences and build these trees using magical stuff like math and algorithms.[7]

Note that, with the above, I am not implying that there's always 100% agreement between different methods and data. For example, back in the day, mitochondrial DNA data suggested the chimp is closer to the gorilla than to us, whereas DNA-DNA hybridization data suggested it's closer to us than the gorilla.[7] But no one doubts that we are all related, or that whatever differences we have are less than 3% even for the least similar parts of our genomes.[7] (Later analyses confirmed that the chimp is in fact more closely related to us than to the gorilla. Rather obvious given their behavior and morphology, if you ask me.)

779px-Me_and_the_Chimp_Reta_Shaw_Buttons_1972-.jpg

Descendant of short-lived line of chimp dentists switches clientele and gives his ancestors' profession a final go. Latest data suggests he still has all his fingers.
Source: Wikimedia Commons Contributors

In fact, humans and chimps — or at least one particular human and one particular chimp — might have been much closer — cozier — than we dare imagine. The DNA comparative techniques showcased above, showed that we got HIV (recognized by its fruits as AIDS - Matthew 7:16) from chimps (SIV).[7] How it happened, no one knows, but I allow my sexual imagination to run wild.

Migratory humans

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#MeToo
Source: Pxhere

It's not just birds who migrate. Humans do it too. And they change skin tones while they're at it.

Like many sequels termed prequels, Homo Sapiens - Origins was released after Homo Sapiens. We started out in the middle of the action, in medias res, and only later discovered our common roots going back to Africa. As with film prequels, many didn't like it, they thought it ruined the aura and mystery of the original by explaining it. To each his own, I guess.

Again, paleontological evidence agrees with DNA evidence, in that it states we all came from Africa. However, the paleontological multiregional hypothesis, as it's called, states that we left Africa as Homo erectus and then became Homo sapiens independently (this already sounds dubious to me), whereas the Out of Africa hypothesis (as it's called) states that there was a second exodus where we left Africa as Homo Sapiens and displaced the earlier Homo erectus.[7] The latter seems to me like a more economical hypothesis.

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Map of human migrations according to the Out of Africa hypothesis. Africa is at the top left. Presumably to help humans migrate using gravity.
Source: Wikimedia Commons Contributors

Further analyses of mitochondrial DNA gave flesh to the now famous 'mitochondrial Eve' and 'Y chromosome Adam'[8], names that were deliberately chosen to confuse theists [reference pending]. Adam and Eve, from whom we're all descended, left Africa around 200,000 years ago, well after Homo erectus had left it, further bolstering the Out of Africa hypothesis.

The Out of Africa hypothesis is far from conclusively proven, and biologists are waiting for more data and some sort of Grand Synthesis, but if quantum physics' and classical physics' lack of success finding a Grand Unifying Theory are to be trusted, we've a long wait ahead of us.

We interbred with Neanderthals

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"Hey, skeleton, eyes are up here."
Source: Wikimedia Commons Contributors, modified (added a censor box, maybe overdid it a bit)

In a series of discoveries that might support (in a proof-of-concept kind of way) the chimpf*cker-who-gave-us-AIDS hypothesis, humans were, most likely this time, cavorting with Neanderthals.[9] It was probably Mitochondrial Eve, if the Bible is to be trusted. (Genesis paints her as one too keen on breaking vows.)

Curtain close

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The harbinger of truth.
Source: Wikimedia Commons Contributors

The Human Genome Project did not directly make the discoveries described above, but it enabled them. And, in the process, it taught us more about who we are. Lessons that are, in some circles, still resisted. There's a paper with the title "Neandertal Demise: An Archaeological Analysis of the Modern Human Superiority Complex", challenging the idea that Neanderthals were brutes inferior to us.

Darwin is one of my heroes. He was prescient beyond measure, and so many years ago was wise and smart enough to avoid the theoretical pitfalls that, mostly biologists right after him, but some even to this day, fall into. Not for nothing did Daniel Dennett call Darwin's theory "the single best idea anyone has ever had". But when Darwin first proposed the idea, and specifically the idea that we're related to apes, it was fiercely resisted.

Darwin (1871) was the first biologist to speculate on the evolutionary relationships between humans and other primates. His view - that humans are closely related to the chimpanzee, gorilla and orangutan - was controversial when it was first proposed and fell out of favor, even among evolutionists, in the following decades. Indeed, biologists were among the most ardent advocates of an anthropocentric view of our place in the animal world [7]

I see the Human Genome Project as mainly a project that vindicates Darwin, that once and for all proves the interconnectedness and common origin of all organisms on Earth.

Plus, you can now go out and tell people "you are a wet airheaded trans cis-sy parasite chimp", and not worry about getting sued — cos science has your back! :P

REFERENCES

1. Wikipedia contributors, "Home Soil," Wikipedia, The Free Encyclopedia, https://en.wikipedia.org/w/index.php?title=Home_Soil&oldid=825937146 (accessed February 22, 2018).

2. Wikipedia contributors, "Body water," Wikipedia, The Free Encyclopedia, https://en.wikipedia.org/w/index.php?title=Body_water&oldid=791849932 (accessed February 22, 2018).

3. Wikipedia contributors, "Noncoding DNA," Wikipedia, The Free Encyclopedia, https://en.wikipedia.org/w/index.php?title=Noncoding_DNA&oldid=826795638 (accessed February 22, 2018).

4. Brown TA. Genomes. 2nd edition. Oxford: Wiley-Liss; 2002. Chapter 15, How Genomes Evolve. Available from: https://www.ncbi.nlm.nih.gov/books/NBK21112/

5. Mills RE, Bennett EA, Iskow RC, et al. Recently Mobilized Transposons in the Human and Chimpanzee Genomes. American Journal of Human Genetics. 2006;78(4):671-679. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1424692/

6. Hu J, Ng PC. Predicting the effects of frameshifting indels. Genome Biology. 2012;13(2):R9. doi:10.1186/gb-2012-13-2-r9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334572/

7. Brown TA. Genomes. 2nd edition. Oxford: Wiley-Liss; 2002. Chapter 16, Molecular Phylogenetics. Available from: https://www.ncbi.nlm.nih.gov/books/NBK21122/

8. Cann RL, Stoneking M, Wilson AC. Mitochondrial DNA and human evolution. Nature. 1987 Jan 1-7;325(6099):31-6. https://www.nature.com/articles/325031a0

9. Yang, M.A.; Malaspinas, A.S.; Durand, E.Y.; Slatkin, M. (2012). "Ancient Structure in Africa Unlikely to Explain Neanderthal and Non-African Genetic Similarity". Molecular Biology and Evolution. 29 (10): 2987–95. doi:10.1093/molbev/mss117. https://academic.oup.com/mbe/article/29/10/2987/1029326

10. Wikipedia contributors, "Transposable element," Wikipedia, The Free Encyclopedia, https://en.wikipedia.org/w/index.php?title=Transposable_element&oldid=820901428 (accessed February 23, 2018).


Earlier Introduction to Biology episodes:

15: The First Physically Mapped Human Gene

14: Sequencing DNA using Gel Electrophoresis

13: Cutting, Pasting, Cloning, and GMOs

12: How a Boy From an Indian Village Broke the Code of Life and Won the Nobel Prize

11: The Most Beautiful Experiment In Biology

10: The Great GATC-by: The Most Famous Science Paper of the 20th Century

9: The Great Kitchen Blender Experiments: How DNA was proved to be the seat of heredity

8: Finding, Counting, and Ordering Genes Using Incredibly Sophisticated Biomolecular Megatechnology

7: Christmas Disease — Yes, it's real, 100% scientifically proven!

6: The Most Famous All-Nighter in the History of Genetics

5: Mendel's Lucky Number Seven — The law of genetics that almost wasn't

4: How Cells Use Logic To Do The Impossible

3 : Armchair Science — The Discovery of Proteins' Secondary Structure

2 : How Cell Membranes Form Spontaneously

1 : Eduard Buchner: The Man Who Killed Vitalism


steemSTEM is the go-to place for science on Steemit. Check it out at @steemstem or browse the #steemSTEM tag or chat live on discord

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@alexander.alexis nice post but you may want to edit this line "The rest of the genome is biologically non-functional, usually called non-coding DNA. " This line a misleading, as we know that a lot of the non-coding DNA does in fact have biological function such as ribosomal RNA genes, micro RNAs, tRNAs, lncRNAs, telomere and centromere sequences etc. The Encyclopedia of DNA Elements (ENCODE) project showed that about 80% of our genome has biological activity.

Yeah I was debating this in my head, and there seems to be some external debate as well! I'll link to this and let people do some of their own research.

I think that the transponsons are equivalent to the inelegant excess codes in modern computer programs.

Back when the cutting edge of programming was compiled on IBM 386 computers, programming code needed to be streamlined and efficient. In our decandent modern day of excess computing power, such careful code editing is unnecessary. Now, codes are pasted on top of each other without regard because the excess computing power overcomes programming obtuseness.

Similarly, when ATP began growing on mitochondrial trees, the biological programming code no longer needed to be elegant. The cells could afford to paste DNA on top of each other without dying of ATP exhaustion in replication or synthesis.

It's true that, by and large, the smaller the organism, the less transposons there are, and at tiny scales the organism must be extremely efficient and can't afford 'junk'.

Thanks for sharing the link. I went to the original paper and did not realize there was so much debate on how molecular biologist and evolutionary biologist define "function".
Cheers!

we are on average 65% water; but if this is a concern to you, you can lower it to 45% by becoming very obese.

If i remember correctly from my biochemestry years, for ea fat molecule we make we use 1 molecule of water, but don't quote me on that, we could also use some creatine to increase the water retation on the muscle tissue

How it happened, no one knows, but I allow my sexual imagination to run wild.

Couldn't they have just ate the chimpaze infected with HIV and for some chance they had a injury in their mouth? Or maybe they got bitten by the chimpanzee, why does it always have to go to sex xD

cavorting with Neanderthals.

This was actually great for us, it increased our genetic pool by a lot and made us able to better survive in the harsh climate from that age

I've actually just learned a little about this in microbiology 2, we are learning how to sequence genes after doing PCR to increase the speed of detection of a bacteria, i think i used a program called blast and used fasta maybe... i really need to learn how to work with that, it was so confusing!! I don't blame the teacher, she had 1 class to explain to us how the program worked...

I really enjoyed the read, it's a topic i like very much! all that cisgender stuff really confuses me though, i hate putting labels on stuff, cisgender, transgender, non-cis-gender, i don't even know anymore, i'm just a human being walking this world with other human being trying to make the world a better place one post at a time!

I'm so happy to see such good content and comments here :-) Keep it up!

Interesting, but I'd say most of this was known before the human genome project, at least twenty plus years ago when I was a student. I had to write a dissertation on the evolution of humans which included reference to mitochondrial Eve and the 'Out of Africa' theory of modern human dispersal.

I must say transposons is a new concept for me, though non-coding 'junk' DNA was known back then.

A well written piece (and I liked the humour). I just thought the whole idea behind the HGP was to gain a better understanding of the diseases that humans are susceptible to and how we might go about controlling them / eradicating them, even. How has it helped in the world of medicine?

Like I mention in the post, it's about consilience. Some of these things were indeed known, but added independent proof won't hurt.

Plus putting the whole mouse genome next to a human genome and comparing them in toto was not possible before the human genome project.

There were cases where the DNA said something slightly different to what more traditional methods said. There was a debate between paleontologists and molecular biologists as to when the split between humans and chimps happened, the former saying 15 million years ago, the latter saying 5 mya; the debate was won by the molecular biologists.

Understanding human diseases was one of the main goals of the HGP, but really it was in a lot of ways a goal unto itself, since the benefits could be many and varied.

Thank you for your input!

Naaah: air is not vacuum! And be aw-air, I can be a rude cisgender (just discovered the word, thanks) physicist! :D

I really enjoyed reading your biology post interlaced with physics jokes all the way to the end! I actually missed reading your texts! :)

Σόρρυ που σου έδωσα μόνο 30 % έχει πέσει επικίνδυνα τονvp :( θα μπω να σε δώσω και από έναν άλλο λογαριασμό :D

The nearthendal guy must be hung like a horse !

Χεχ! No problem, δεν είμαι απ' αυτούς, δεν τα πολυκοιτάω αυτά, αν δεν δίνεις κάποιο λόγο έχεις, έχει τόσους και τόσους που πρέπει να ψηφιστούν!

Το παραμάνα αυτές τις μέρες 😂😂🤣🤣

Excellent post. Good to know that when insults can be backed up by science they are okay... as long as you keep your science updated, obviously.
I must say I had to really laugh out loud when those airplanes came up. Genius!

Interesting post. Thank you.

I laughed at the Neanderthal, I'm sure it wasn't that big.....

Kalispera.. foveto athro..

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well, ​I think we can say love is love since the stone age. A really interesting read, well done!

Μπράβο σου @alexander.alexis! Πολύ καλή δημοσίευση!