Less is More? Conserved Deletions as Drivers of Human Evolution

Category Science

tldr #

Recent findings by scientists from Yale and the Broad Institute of MIT and Harvard suggest that the human genome differences compared to other primates, specifically in the form of pairs of conserved deletions, have contributed to our evolution. Using Massively Parallel Reporter Assays (MPRA), the team identified 10,000 bits of genetic information and 800 hCONDELs that conferred differences in regulatory activity, which have the potential to impact brain development in humans.

content #

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? .

The closest primate relative to humans are chimpanzees

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.

The research is part of an international undertaking called 'Zoonomia Project' which seeks to better understand the evolution of mammals

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.

Massively Parallel Reporter Assays (MPRA) is used to measure the activity of multiple DNA sequences

"[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.

The team discovered 800 human-specific conserved deletions of an average base pair of 2.56

"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 .

The deleted sequences relate to genes involved in neuronal and cognitive functions such as the development of the brain

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 interrogate the functional effects of conserved deletions underlying human traits.

The team highlighted several hCONDELs with putative effects on brain development, such as HDAC5, CPEB4, and PPP2CA

hashtags #
worddensity #