Genome study reveals what we "lack" makes us who we are

We lack some genetic sequences mice and whales and most other species have. How has this not disrupted human biology?
Amal Jos Chacko
DNA helix.jpg
DNA helix.


As a species, humans tend to focus on the additions and insertions when we think in terms of improvements and how we’ve got to this point. 

Recent developments have contributed to the collection of data from genomes of different species, leading to scientists studying primate DNA and identifying additions specific to the human genome, including the gene responsible for our ability to speak.

But don’t the deletions play a role too?

Researchers at Yale and the Broad Institute of MIT and Harvard think yes.

Their findings, published in the journal Science, talk about how differences in the human genome compared to other primates contributed to our evolution.

Led by James Xue of the Broad Institute, the team identified about 10,000 bits of genetic information, most of them as small as a few base pairs of DNA, that differentiate humans from chimpanzees, the closest primate relative to humans. 

These missing bits, some of which relate to genes involved in neuronal and cognitive functions, including the development of the brain, were observed to be a common occurrence in all humans.

The authors suggest that the absence of these across our species signifies some biological advantage.

Less is more?

“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,” Steven Reilly, assistant professor of genetics at Yale School of Medicine and senior author of the paper, told Yale News.

“[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 added.

Reilly explained how deletion of information is analogous to removing characters from a word to create new words, such as “is” from “isn’t”.

The team used Massively Parallel Reporter Assays (MPRA)— a powerful, high-throughput method to measure the activity of multiple DNA sequences— to simultaneously screen and measure the function of thousands of genetic changes among subjects.

“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 clarified.

The team’s research is part of the Zoonomia Project an international undertaking providing new insights into the evolution of mammals and using these to develop new treatments for human diseases and protect endangered species.

Study Abstract

Conserved genomic sequences disrupted in humans may underlie uniquely human phenotypic traits. We identified and characterized 10,032 human-specific conserved deletions (hCONDELs). These short (average 2.56 base pairs) deletions are enriched for human brain functions across genetic, epigenomic, and transcriptomic datasets. Using massively parallel reporter assays in six cell types, we discovered 800 hCONDELs conferring significant differences in regulatory activity, half of which enhance rather than disrupt regulatory function. We highlight several hCONDELs with putative human-specific effects on brain development, including HDAC5, CPEB4, and PPP2CA. Reverting an hCONDEL to the ancestral sequence alters the expression of LOXL2 and developmental genes involved in myelination and synaptic function. Our data provide a rich resource to investigate the evolutionary mechanisms driving new traits in humans and other species.

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