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Men Regain Evolutionary Driver's Seat -- Mutation Study Confirms Strong Male-Driven Evolution Among Humans And Apes

Date:
April 15, 2002
Source:
University Of Chicago Medical Center
Summary:
Researchers from the University of Chicago have estimated that genetic mutations – the raw material for evolution – occur 5.25 times more often in males than in females. This discovery should lay to rest any doubts raised by recent studies questioning the dominant role males play in producing mutations for molecular evolution.

Researchers from the University of Chicago have estimated that genetic mutations – the raw material for evolution – occur 5.25 times more often in males than in females. This discovery should lay to rest any doubts raised by recent studies questioning the dominant role males play in producing mutations for molecular evolution.

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Their study, published in the April 11 issue of Nature, also shows that these mutations are caused mainly by random errors that occur during cell divisions rather than by environmental factors.

"Mutation is the ultimate source of variation," says Wen-Hsiung Li, Ph.D., the George Wells Beadle Distinguished Service Professor in the department of ecology and evolution at the University of Chicago. "Your ancestors and my ancestors accumulated different mutations, which is part of the reason why you and I look different."

For more than half a century, scientists have believed the main source of new mutations is in the male germ line. But two recent studies – one from the Whitehead Institute (2000) and the other from the International Human Genome Sequence Consortium (2001) – suggest the male-female ratio of mutation rate – or alpha – is only about 2-to-1, a drastic decrease from earlier estimates. Li and co-investigator Kateryna Makova, Ph.D., research associate in the department of ecology and evolution, have restored the validity of a high alpha among humans and apes.

Li and Makova studied part of the DAZ locus, a non-coding genetic sequence present on chromosome 3 and the Y chromosome. The researchers found a low male-female mutation rate when they compared closely related species, which involved a shorter evolutionary time span. For example, when they looked at humans, pygmy chimpanzees and gorillas, they found that alpha is only 1.4, which suggests there is only a slightly higher mutation rate in males than in females.

But for distantly related species, which, according to Li, better represent the general trend over evolutionary time, alpha is always high. This is consistent with earlier studies that also looked at distant species.

The study from the Whitehead Institute only compared closely related sequences from species that diverged after the point when human and chimpanzee split about 5 million years ago.

"One problem with this study is that they used a wrong gene genealogy," Makova says. "Also, it’s inappropriate to use closely related species because of ancient-nucleotide polymorphism." This means at the time of speciation, there already were mutations accumulating on chromosome 3. But the Y chromosome, which had virtually no polymorphism, did not start accumulating errors until the point of speciation. "When you account for ancient-nucleotide polymorphism, alpha increases drastically."

The Consortium study did not correct for multiple mutations that accumulated at the same site. Li and Makova corrected for this statistical error.

Not only are the two recent estimates significantly smaller than the earlier estimates, but they are also smaller than the estimate of alpha in carnivores, like dogs and cats (4) and birds (5). This conflicts with the generation-time effect hypothesis, which suggests that the molecular clock runs faster in organisms with a shorter generation time because they undergo a larger number of cell divisions per unit of time. So, for example, rodents have a faster molecular clock than humans.

"We would expect alpha to be higher in primates than in carnivores and birds because in primates there is a larger difference in the number of cell divisions between egg cells and sperm cells than in carnivores and birds," Makova said. "So these two new estimates didn’t make sense."

Li and Makova’s study is the first to calculate the male-female mutation rate without using the X chromosome. "Some have argued that the high alpha could be due to a reduction in mutation rate in X rather than an elevated rate in Y," they note in their paper. So in this study the researchers compared the Y chromosome with an autosome – an asexual chromosome – eliminating the X factor altogether.

"This is independent proof of the dominant male in producing mutations for molecular evolution," Makova says.

The study also suggests mutations are "replication-driven" – caused mainly by cell divisions and not environmental factors. Since cell divisions are continuous during a man’s life, his sperm stem cells constantly accumulate errors – or mutations. In contrast, there are only 24 cell divisions that occur in the egg cells of a woman, most of which take place before she is born.

"Since mutations seem to occur in the male germ line," Li says, "then replication errors are important and environmental factors are less important."

Since mutations in sperm cells accumulate as a man ages, does the biological clock tick faster for men as it does for women? Yes, but it’s not something worth worrying about, according to Li.

"The mutation rate is very low, so the increase in mutations in an individual male is not appreciable," he says, "even if you were to double or triple the rate."

Most mutations have no effect on a person’s health or survival, but merely accumulate within your DNA, according to Li. "This is because more than 90 percent of the human genome is non-coding. But mutations – bad, good or neutral – accumulate in the genome of a species – whether it’s bird, chimp or human."


Story Source:

The above story is based on materials provided by University Of Chicago Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Chicago Medical Center. "Men Regain Evolutionary Driver's Seat -- Mutation Study Confirms Strong Male-Driven Evolution Among Humans And Apes." ScienceDaily. ScienceDaily, 15 April 2002. <www.sciencedaily.com/releases/2002/04/020412080629.htm>.
University Of Chicago Medical Center. (2002, April 15). Men Regain Evolutionary Driver's Seat -- Mutation Study Confirms Strong Male-Driven Evolution Among Humans And Apes. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2002/04/020412080629.htm
University Of Chicago Medical Center. "Men Regain Evolutionary Driver's Seat -- Mutation Study Confirms Strong Male-Driven Evolution Among Humans And Apes." ScienceDaily. www.sciencedaily.com/releases/2002/04/020412080629.htm (accessed November 28, 2014).

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