Scientists uncover a trove of genes that could hold key to how humans evolved

Scientists uncover a trove of genes that could hold key to how humans evolved
Image depicts motif divergence between human transcription factors and their counterparts in other species. The blue section in the pie charts represents a proportion of transcription factors, across different classes, which are dissimilar in human. Credit: Sam Lambert

Researchers at the Donnelly Centre in Toronto have found that dozens of genes, previously thought to have similar roles across different organisms, are in fact unique to humans and could help explain how our species came to exist.

These code for a class of proteins known as transcription factors, or TFs, which control gene activity. TFs recognize specific snippets of the DNA code called motifs, and use them as landing sites to bind the DNA and turn genes on or off.

Previous research had suggested that TFs which look similar across different organisms also bind similar motifs, even in as diverse as and humans. But a new study from Professor Timothy Hughes' lab, at the Donnelly Centre for Cellular and Biomolecular Research, shows that this is not always the case.

Writing in the journal Nature Genetics, the researchers describe a new computational method which allowed them to more accurately predict motif sequences each TF binds in many . The findings reveal that some sub-classes of TFs are much more functionally diverse than previously thought.

"Even between closely related species there's a non-negligible portion of TFs that are likely to bind new sequences," says Sam Lambert, former graduate student in Hughes' lab who did most of the work on the paper and has since moved to the University of Cambridge for a postdoctoral stint.

"This means they are likely to have novel functions by regulating different genes, which may be important for species differences," he says.

Even between chimps and humans, whose genomes are 99 per cent identical, there are dozens of TFs which recognize diverse motifs between the two species in a way that would affect expression of hundreds of different genes.

"We think these molecular differences could be driving some of the differences between chimps and humans," says Lambert, who won the Jennifer Dorrington Graduate Research Award for outstanding doctoral research at U of T's Faculty of Medicine.

To reanalyze motif sequences, Lambert developed new software which looks for structural similarities between the TFs' DNA binding regions that relate to their ability to bind the same or different DNA motifs. If two TFs, from different species, have a similar composition of amino-acids, building blocks of proteins, they probably bind similar motifs. But unlike older methods, which compare these regions as a whole, Lambert's automatically assigns greater value to those amino-acids— a fraction of the entire region— which directly contact the DNA. In this case, two TFs may look similar overall, but if they differ in the position of these key amino-acids, they are more likely to bind different motifs. When Lambert compared all TFs across different species and matched to all available motif sequence data, he found that many human TFs recognize different sequences—and therefore regulate different genes— than versions of the same proteins in other animals.

The finding contradicts earlier research, which stated that almost all of human and fruit fly TFs bind the same motif sequences, and is a call for caution to scientists hoping to draw insights about human TFs by only studying their counterparts in simpler organisms.

"There is this idea that has persevered, which is that the TFs bind almost identical motifs between humans and fruit flies," says Hughes, who is also a professor in U of T's Department of Molecular Genetics and Fellow of the Canadian Institute for Advanced Research. "And while there are many examples where these proteins are functionally conserved, this is by no means to the extent that has been accepted."

As for TFs that have unique human roles, these belong to the rapidly evolving class of so-called C2H2 zinc finger TFs, named for zinc ion-containing finger-like protrusions, with which they bind the DNA.

Their role remains an open question but it is known that organisms with more diverse TFs also have more cell types, which can come together in novel ways to build more complicated bodies.

Hughes is excited about a tantalizing possibility that some of these zinc finger TFs could be responsible for the unique features of human physiology and anatomy—our immune system and the brain, which are the most complex among animals. Another concerns sexual dimorphism: countless visible, and often less obvious, differences between sexes that guide mate selection—decisions that have an immediate impact on reproductive success, and can also have profound impact on physiology in the long term. The peacock's tail or facial hair in men are classic examples of such features.

"Almost nobody in human genetics studies the molecular basis of , yet these are features that all human beings see in each other and that we are all fascinated with," says Hughes. "I'm tempted to spend the last half of my career working on this, if I can figure out how to do it!"


Explore further

A surprizing finding shines new light on the largest group of human proteins

More information: Similarity regression predicts evolution of transcription factor sequence specificity, Nature Genetics (2019). DOI: 10.1038/s41588-019-0411-1 , https://www.nature.com/articles/s41588-019-0411-1
Journal information: Nature Genetics

Citation: Scientists uncover a trove of genes that could hold key to how humans evolved (2019, May 27) retrieved 18 August 2019 from https://phys.org/news/2019-05-scientists-uncover-trove-genes-key.html
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May 27, 2019
"Sexual dimorphism, a phenotypic difference between males and females of the same species"

The Male gender and Female gender of most species are the NATURAL outcome for the survival of the species, whether human or fruit fly. There is no alternative to this. It is these two genders that enable and promote the ability to procreate, where the male of the specie provides the sperm that is deposited into the female for the main purpose of the survival of the specie and genus.
It is completely LOGICAL scientifically as well as morally between one man and one woman in the human genus.
For this reason, homosexuality and transgenderism are ILLOGICAL due to their primary basis in emotion and feelings, with no possibility of NATURAL PROCREATION without unnatural means such as surrogacy arrangements.

May 27, 2019
These 'zinc-fingers' could appear to be evidence of biological engineering at the DNA level that may have occurred in our remote past. Likely about 12,500 years ago. Possibly sometime after or before a conjectured cosmic event that brought on the 'Younger Dryas' period, climatologically. Possibly a meteor strike. Just a theory, but IMHO a species looking after us knew that we would need to be, and were ready for, intervention to give us our 'soul carriers' as part of their (our alien friends) own prime direstive.... to seek out and find intelligent species ready for their own souls so they could eventually become cosmic citizens like Konstantin Tsiolkovskiy envisioned in the late 1800's.

May 28, 2019
As expected since transcription regulation is a generic rapid evolutionary mechanism; other downstream examples is transcript regulation (pro-mRNA and mRNA handling) and perhaps ribosomal functions that can delay translation et cetera (dunno about the evolutionary rates there).

The blind tinkering has purely coincidentally resulted in something somewhat analogous to the evolution of the animal Hox box, which diversified and in modular fashion affect body segments. Plants and even our sister clade fungus evolved entirely different "body plan" mechanisms. Here transcription factors diversify and in modular fashion affects transcription factor motifs; prokaryotes evolved differently of course.

May 28, 2019
Humans did not evolve they were domesticated in the context of the tribe. They share specific and unique genes with other domesticated species. Researchers should be approaching their work from this perspective.

Dogs did not evolve they were consciously, artificially selected for certain traits. It is exactly the same with humans and it has been the case throughout their existence.

May 28, 2019
The Male gender and Female gender of most species are the NATURAL outcome for the survival of the species, whether human or fruit fly
This freak knows nothing about this subject. She returns periodically under different socks to post obviously fake, insane nonsense for the purpose of discouraging legitimate participants.

Why are you vandalizing this site? Who do you work for?

May 29, 2019
For this reason, homosexuality... are ILLOGICAL due to their primary basis in emotion and feelings, with no possibility of NATURAL PROCREATION without unnatural means such as surrogacy arrangements.


Whether it is logical to you or not is inconsequential. Homosexuality occurs in many other species as well. By the way, you hurt your own argument when you randomly capitalize words. Don't you get tired of looking stupid?

May 30, 2019
Whether it is logical to you or not is inconsequential. Homosexuality occurs in many other species as well
Gaydom is likely one of many biological responses to overgrowth. Mothers perceive overcrowding and a shortage of resources for their existing children, and in effect neuter future offspring in the womb epigenetically. They can still work and fight to support the tribe while not adding to its ecological burden by reproducing.

And gays remain able to reproduce should the tribe need to quickly replace members lost in conflict. Tribes with this capacity would have an obvious advantage over those that did not.

May 31, 2019
For this reason, homosexuality... are ILLOGICAL due to their primary basis in emotion and feelings, with no possibility of NATURAL PROCREATION without unnatural means such as surrogacy arrangements.


Whether it is logical to you or not is inconsequential. Homosexuality occurs in many other species as well. By the way, you hurt your own argument when you randomly capitalize words. Don't you get tired of looking stupid?
says Bojingles

It got your attention in the meantime. Many things are of no great consequence. YOUR opinion is a good example.
You seem to be in favour of homosexuality. Is it because some animals have been observed taking part in same-sex intercourse? Or are you in favour of homosexual acts for some other reason? Are you gay?
The LGBT lobby grows stronger each year. Eventually they will have legislation made so that they will be free to sodomise boys as young as 12 or younger. The Democrat Party will not refuse them and the nation will be finished

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