The best way to study human evolution is not from looking at human genes, but from comparing ours with non-natural species that – genetically speaking – are close relatives. The closeness of genes allows scientists to study in detail the unique thing that makes us human.
And in contrast to chimpanzees, what makes us special seems to be our great potential for serious mental illnesses and strange facial shapes, according to two new studies published in the journals. Nature, and The genetics of nature, separately.
Human brains developed for disease, unlike chimpanzees
In particular, the researchers found a significant difference in the expression of the SSTR2 gene, which alters the activity of neurons in the cerebral cortex – and has shown links in humans to neuropsychiatric diseases (such as Alzheimer’s dementia and dementia). schizophrenia) – in addition to the EVC2 gene, which gives us the strange, human shape.
“It is important to study human evolution, not only to understand where we came from, but also why humans are getting so many diseases not seen in other species,” said a student. recent Stanford graduate Rachel Agoglia and lead author of the Nature study.
The Agoglia study examines a new device that binds human and chimpanzee skin cells modified to function as gas cells – which are highly accessible and potentially transformed into a broad spectrum of other cell types. Of course, they cannot grow into a whole organism.
“These cells serve a very important specific purpose in this type of study by allowing us to accurately compare human and chimpanzee genes and their side-by-side functions,” said Professor Co. Hunter of the Stanford School of Humanities and Sciences, according to a Phys.org report. Fraser is the lead author on the The genetics of nature paper and co-author of the Nature paper by Sergiu Pașca, associate professor of mental and behavioral sciences at Stanford School of Medicine.
Forcing human neurons to become ‘organoids’
Fraser’s laboratory is particularly interested in how the genetics of humans and other primates compare at what is known as the “tax-regulatory” elements, which determine the expression of other genes in a surrogate. – located on the same chromosome, or molecular DNA). The other method – called cross-regulatory factors – can also regulate genes that are present on other chromosomes elsewhere in the genome. However, cross-regulatory factors (such as proteins) are less likely to reveal different expressions among closely related species of the regulatory factors.
However, even when cell-like cells from chimpanzees and humans are available, there is still a risk that a number of factors may interfere with it. For example, small gender differences in developmental time can severely hamper the study of brain development, Pașca explained in the Phys.org report. Because human brains and mature chimpanzees are at very different stages and we do not have a proper way of comparing them directly, it is not easy to do a comparison-and-compare study. But placing chimpanzee and human DNA inside the same cellular nucleus will allow scientists to eliminate most of the objects of study concern.
Agoglia coaxed the cells to form cortical spheroids – also known as organoids – which are bundles of brain cells capable of inhibiting the growth of mammalian cerebral cortex.
“The human brain is largely accessible at the molecular and cellular level for most development, so we introduced cortical spheroids to help us access these important processes,” Pașca said. , who is also Bonnie Uytengsu and Family Director of Stanford Brain Organogenesis.
A new invention may help reduce brain diseases
The researchers found thousands of genes that expressed cis-regulatory differences between the sexes over a 200-day growth period in stem-cell brain organoids. They then decided to dive deeper into one of these genes – SSTR2 – which has been more accurately expressed in human neurons, acting as receptors for a neurotransmitter called somatostatin. Later comparisons between chimpanzee and human cells revealed elevated protein expression of the SSTR2 gene within human cortical cells. And when the researchers applied a small molecular drug that binds to SSTR2 into the human and chimpanzee cells, the human neurons responded much more than the chimpanzee ones.
“Evolution of the primary brain may have added sophisticated neuromodulatory features to neural circuits, which may be disturbed under certain conditions and more susceptible to neuropsychiatric disease,” Pașca explained.
This is important because it may be possible to alter human neurons in cortical circuits with neurotransmitters. And most importantly, “neuromodular” activity may be associated with psychiatric disorders, as SSTR2 is involved in brain diseases. Since these brain vulnerabilities occurred when our evolutionary pathway changed from other hominids, it may one day be able to reduce human brain vulnerability to mental illness. As long as mental illness is a bug – and not a feature – of the human brain.