Mankind’s Missing Puzzle Pieces: The “Deleted” Genes That Made Us Human

DNA Technology Concept

A new study explores the significance of the genetic information absent in the human genome compared to other primates. The researchers found that humans lost around 10,000 fragments of genetic information over evolutionary history, which differentiate us from our closest primate relatives, like chimpanzees. Some of these “deleted” fragments relate to neuronal and cognitive functions, including those involved in brain cell formation. These deletions, present in other mammals but absent in humans, became conserved across all humans, suggesting they provided a biological advantage. The team used Massively Parallel Reporter Assays (MPRA) technology to screen and measure the function of thousands of genetic changes among species, contributing to our understanding of what makes humans unique.

Researchers from Yale and the Broad Institute discovered that the loss of about 10,000 fragments of genetic information differentiates humans from our closest primate relatives. These conserved deletions, associated with cognitive functions and brain cell formation, suggest an evolutionary advantage, altering the function of our genes and potentially contributing to our unique human characteristics.

What the human genome is lacking compared with the genomes of other primates might have been as crucial to the development of humankind as what has been added during our evolutionary history, according to a new study led by researchers at Yale and the Broad Institute of MIT and Harvard.

The new findings, published recently in the journal Science, fill an important gap in what is known about historical changes to the human genome. While a revolution in the capacity to collect data from genomes of different species has allowed scientists to identify additions that are specific to the human genome — such as a gene that was critical for humans to develop the ability to speak — less attention has been paid to what’s missing in the human genome.

For the new study researchers used an even deeper genomic dive into primate DNA to show that the loss of about 10,000 bits of genetic information — most as small as a few base pairs of DNA — over the course of our evolutionary history differentiate humans from chimpanzees, our closest primate relative. Some of those “deleted” pieces of genetic information are closely related to genes involved in neuronal and cognitive functions, including one associated with the formation of cells in the developing brain.

These 10,000 missing pieces of DNA — which are present in the genomes of other mammals — are common to all humans, the Yale team found.

The fact that these genetic deletions became conserved in all humans, the authors say, attests to their evolutionary importance, suggesting that they conferred some biological advantage.

“Often we think new biological functions must require new pieces of DNA, but this work shows us that deleting genetic code can result in profound consequences for traits make us unique as a species,” said Steven Reilly, an assistant professor of genetics at Yale School of Medicine and senior author of the paper.

The paper was one of several published in the journal Science from the Zoonomia Project, an international research collaboration that is cataloging the diversity in mammalian genomes by comparing DNA sequences from 240 species of mammals that exist today.

In their study, the Yale team found that some genetic sequences found in the genomes of most other mammal species, from mice to whales, vanished in humans. But rather than disrupt human biology, they say, some of these deletions created new genetic encodings that eliminated elements that would normally turn genes off.

The deletion of this genetic information, Reilly said, had an effect that was the equivalent of removing three characters — “n’t” — from the word “isn’t” to create a new word, “is.”

“[Such deletions] can tweak the meaning of the instructions of how to make a human slightly, helping explain our bigger brains and complex cognition,” he said.

The researchers used a technology called Massively Parallel Reporter Assays (MPRA), which can simultaneously screen and measure the function of thousands of genetic changes among species.

“These tools have the capability to allow us to start to identify the many small molecular building blocks that make us unique as a species,” Reilly said.

Reference: “The functional and evolutionary impacts of human-specific deletions in conserved elements” by James R. Xue, Ava Mackay-Smith, Kousuke Mouri, Meilin Fernandez Garcia, Michael X. Dong, Jared F. Akers, Mark Noble, Xue Li, Zoonomia Consortium†. , Kerstin Lindblad-Toh, Elinor K. Karlsson, James P. Noonan, Terence D. Capellini, Kristen J. Brennand, Ryan Tewhey, Pardis C. Sabeti, Steven K. Reilly, Gregory Andrews, Joel C. Armstrong, Matteo Bianchi, Bruce W. Birren, Kevin R. Bredemeyer, Ana M. Breit, Matthew J. Christmas, Hiram Clawson, Joana Damas, Federica Di Palma, Mark Diekhans, Michael X. Dong, Eduardo Eizirik, Kaili Fan, Cornelia Fanter, Nicole M. Foley, Karin Forsberg-Nilsson, Carlos J. Garcia, John Gatesy, Steven Gazal, Diane P. Genereux, Linda Goodman, Jenna Grimshaw, Michaela K. Halsey, Andrew J. Harris, Glenn Hickey, Michael Hiller, Allyson G. Hindle, Robert M. Hubley, Graham M. Hughes, Jeremy Johnson, David Juan, Irene M. Kaplow, Elinor K. Karlsson, Kathleen C. Keough, Bogdan Kirilenko, Klaus-Peter Koepfli, Jennifer M. Korstian, Amanda Kowalczyk, Sergey V. Kozyrev, Alyssa J. Lawler, Colleen Lawless, Thomas Lehmann, Danielle L. Levesque, Harris A. Lewin, Xue Li, Abigail Lind, Kerstin Lindblad-Toh, Ava Mackay-Smith, Voichita D. Marinescu, Tomas Marques-Bonet, Victor C. Mason, Jennifer R. S. Meadows, Wynn K. Meyer, Jill E. Moore, Lucas R. Moreira, Diana D. Moreno-Santillan, Kathleen M. Morrill, Gerard Muntané, William J. Murphy, Arcadi Navarro, Martin Nweeia, Sylvia Ortmann, Austin Osmanski, Benedict Paten, Nicole S. Paulat, Andreas R. Pfenning, BaDoi N. Phan, Katherine S. Pollard, Henry E. Pratt, David A. Ray, Steven K. Reilly, Jeb R. Rosen, Irina Ruf, Louise Ryan, Oliver A. Ryder, Pardis C. Sabeti, Daniel E. Schäffer, Aitor Serres, Beth Shapiro, Arian F. A. Smit, Mark Springer, Chaitanya Srinivasan, Cynthia Steiner, Jessica M. Storer, Kevin A. M. Sullivan, Patrick F. Sullivan, Elisabeth Sundström, Megan A. Supple, Ross Swofford, Joy-El Talbot, Emma Teeling, Jason Turner-Maier, Alejandro Valenzuela, Franziska Wagner, Ola Wallerman, Chao Wang, Juehan Wang, Zhiping Weng, Aryn P. Wilder, Morgan E. Wirthlin, James R. Xue, Xiaomeng Zhang, 28 April 2023, Science.
DOI: 10.1126/science.abn2253

James Xue of the Broad Institute is lead author of the study.

7 Comments on "Mankind’s Missing Puzzle Pieces: The “Deleted” Genes That Made Us Human"

  1. Interestingly, some of the same phraseology appears on artificial intelligence commentary. Somehow, humans can alter programming, add chips, modified chips, and change operating programs. And yet, humanity has to evolve on its own, without any help from intelligent design! Isn’t that hypocritical in itself? Everyone worries about artificial intelligence turning on its creators, but isn’t that what humanity has done? Turned on its creator?

  2. Why don’t you just believe the truth that God made everything as we see it today. He made humans exactly as they are in the beginning.

  3. Nicholas Kafouris | June 9, 2023 at 1:18 am | Reply

    As a Physiologist who has studied quite deeply the evidence, I find NO conflict between Creation and Science; rather, the evidence us against evolution. Creationists and evolutionists both use the SAME evidence but have different worldviews to interpret it.
    Remember, to be able to ‘do’ science we must use Rationality, laws of Logic, the Uniformity if Nature, have preconditions of Intelligebility, to say nothing of Morality and Ethics. All these are NON-MATERIALISTIC and have NO basis in Physics or Chemistry, BUT have their origin in a Supreme supernatural Intelligent BEING: GOD, Who alone can account for these factors and conditions. This Being is none other than the Lord Jesus Christ, the Creator God Who gave all these things and Who upholds the Universe too.
    Why ,oh why, is there such a mental block by so many to being able to see His hand in ALL this?
    This NON-MATERIALISTIC, side us an ultimate proof that God exists and is He Who us revealed to us in the Bible that alone can truly account for the Universe’s and Life’s origins, as it alone provides a Rational, Logical BASIS for ALL that we can see, think about what we CANNOT see, for being ABLE to study and the Consistency in all we can do.
    Thank you.

  4. Well in answer to some of the commentary queries about “just believe God did it” – that sounds so nice doesn’t it. Lady, look up up the etymology of the word nice.
    There are documented cuneiform tablets that tell the story of an unimaginably intelligent race of beings who came to earth and “fiddled” with Hominid DNA to make a “worker” type being that could follow directions. Then some of these intelligent beings actually ended up mating with the humanoids they had created and then came humans with Supreme intelligence and capability. But some of the unearthly beings (Creators, DNA manipulators) were afraid of this because it made us more powerful than they. So they’ve been trying to kill us off, save us, re-manipulate our DNA, and many other things ever since THEY couldn’t agree on what to do with us. We were the miners of all the precious metals they need on their planet….. so yes, they removed, added, shortened telomeres,tellers, and added some of theirs. So out of Africa and monkey stories are null and void

  5. I just love the fact that an article about the human genome is always bound to spark a debate about science fiction. Let’s keep to the facts, they are more amazing than any made-up stories a human can ever come up with!

Leave a comment

Email address is optional. If provided, your email will not be published or shared.