Gene Study Shows Losses May Have Provided Opportunities For Changes That Otherwi

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Gene Study Shows Losses May Have Provided Opportunities For Changes

That Otherwise Could Not Have Occurred

http://www.medicalnewstoday.com/medicalnews.php?newsid=37744

Humans and chimps share most of their genes, yet they differ

dramatically in many ways---their walk, the sizes of their brains and

their capacities for speech and language, for example.

Scientists would like to know how and when such differences arose,

and new research from the University of Michigan shows how one

process---gene loss---may have figured in.

The work, by a group led by associate professor of ecology and

evolutionary biology Jianzhi Zhang, is reported in the Feb. 14 issue

of the open-access journal PLoS Biology.

Researchers who speculate about human origins have come up with three

main scenarios for how we ended up with our unique traits, Zhang

said. The first possibility is that we acquired completely new genes

that other apes don't have. Another is that some of our genes have

taken on different functions through mutation.

It's also possible that we humans lost some genes along the way, and

those losses provided opportunities for changes that otherwise could

not have occurred. For example, scientists have shown that over the

course of evolution, humans lost a gene that produces a particular

jaw muscle protein. Perhaps the loss of that gene gave us smaller jaw

muscles, making room in our skulls for bigger brains.

That's just speculation, and until now there was no concrete evidence

for the " less is more hypothesis " that losing certain genes offered

tangible benefits, Zhang said. " So we wanted to know how many genes

have been lost and what kinds of genes have been lost in human

evolution, and second, whether any of those gene losses was a good

thing. "

Zhang's group started by scrutinizing a database of human pseudogenes-

--stretches of DNA that look like known genes but don't function as

genes. Then the researchers weeded out pseudogenes that never had

been functional in any organism. From those that remained, they

further narrowed the field to only those human pseudogenes that had

working counterparts in chimpanzees and also had mutations in places

that would render the human versions inactive. They ended up with 67

human-specific pseudogenes, to which they added 13 that had been

reported in the literature but not included in the original database,

bringing the total to 80.

Next, Zhang and his team consulted another database called Gene

Ontology, which lists the functions of all genes for which such

information is known. That's when things got interesting. Instead of

a random assortment of genes with various functions, they found that

genes related to the sense of smell and the ability to taste

bitterness were overrepresented in the collection of human

pseudogenes. So were genes concerned with the immune response. The

findings made sense to Zhang.

" We know that humans have reduced olfactory sensitivity, so the

finding is consistent with that observation. Also, in a previous

paper we showed that bitter taste receptor genes tended to become

unimportant in humans, and we put forth a hypothesis to explain why:

The ability to taste bitterness is important for detecting toxins in

food, and most of those toxins are in plants. About 1 to 2 million

years ago, we started eating more meat rather than plants, and also

there was use of fire, which can detoxify foods. "

Loss of function also is expected in genes related to the immune

response. " Immune system genes respond to pathogens, which change

rapidly, so the genes also change rapidly, " Zhang said. " If the

pathogen is no longer there, then you don't need the immune system

gene in the host. "

Having identified lost genes and their functions, the researchers

next wanted to figure out whether losing the genes benefited humans

in any way. Studies on mice suggested that loss of a gene called MBL1-

--which is present and functional in rhesus monkeys and chimps as

well as mice, but has lost its function in humans---might confer

protection against severe bacterial infection in the blood (sepsis).

But humans lost that gene so long ago, it was hard to pinpoint the

evolutionary forces behind the loss.

So the researchers focused their attention on another human-specific

pseudogene, CASPASE12. Work by other researchers had shown that the

gene has completely lost its function in non-Africans, but a small

percentage of Africans and African Americans have a functional copy

of the gene. Interestingly, people who lack the gene are better able

to resist sepsis than those who have a working copy.

" This is another indication that loss of the gene would be good for

the individual, but it doesn't show that the gene became a pseudogene

because of that advantage. " However, using population genetics

techniques, the researchers were able to demonstrate just that. They

also determined when the loss occurred---somewhere between 51,000 and

74,000 years ago---which is consistent with the idea that it happened

not long before humans began migrating out of Africa 40,000 to 60,000

years ago.

As for exactly how lacking the gene---which appears to be essential

in all mammals except humans---became more advantageous than having

the gene, Zhang believes he has an answer.

The immune system, he explained, must constantly be turned up or down

to give the proper response. " It's a delicate balance---you don't

want it too strong or too weak. " The normal function of CASPASE12 is

to keep the response from being too strong, and that probably served

humans well at one time. But then, " during human evolution, either

because of an environmental change or because of some other genetic

changes in the human genome, the balance was broken, so that having

the gene makes the response too low, and you can't fight infection, "

Zhang said. " If the gene is lost, the response returns to normal, and

so does the ability to fight infection. "