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· Meiosis (Spermatogenesis/Oogenesis)—What happens to the chromosomes during meiosis? How do meiosis and sexual reproduction increase genetic variation?

· Punnett Squares for ALL types of genetic crosses—How do you determine the alleles the parents can pass to their offspring? What information about offspring genotypes and phenotypes do Punnett Squares give us? What is probability?

· DNA Structure and the Central Dogma of Biology—What are the parts of DNA? How are they put together? What occurs during both transcription and translation? What is the purpose of these processes? Explain how a protein is put together through these processes.

· DNA Electrophoresis and the Elephant Lab—How do restriction enzymes work? What happens to DNA when run on a gel? What information do DNA banding patterns tell us?

· Pedigree Analysis—What is a genetic pedigree? What do the different pedigree symbols (circle, square, etc.) mean? Why are pedigrees used?

· “Journey of Man”—What is a genetic marker? What can genetic markers help us understand about human evolution?

· The biochemistry of genetic diseases—Explain how genes can create the symptoms of disorders like Sickle Cell Anemia, Cystic Fibrosis, Huntington’s, Hemophilia, and Methemoglobinemia (Blue People disorder.)

Sunday, February 10, 2002, 12:00 a.m. Pacific

Studying an evolution perplexity: Why do harmful genes survive?

BALTIMORE — If Darwin was right, and evolution relentlessly weeds out genetic traits that impede a species' survival, why are one-quarter of adult Europeans and 90 percent of Asians unable to digest milk products — a rich, year-round source of protein and energy?

Why are 3 percent of U.S. children struggling in school, distracted by attention-deficit hyperactivity disorder? Why does one in 28 people of European descent carry the gene for cystic fibrosis?

Scientists don't have all the answers. But the recently completed mapping of the human genome, and the decreasing costs of the DNA sequencing technology that made it possible, have energized new research in evolutionary genetics. Scientists are gaining intriguing glimpses into the cold logic of human evolution, and the remarkably complex interplay of genetics and human history.

The new genetic tool kit "puts this whole area of research on a more scientific basis, rather than pure speculation," said biochemist Robert Moyzis, of the University of California, Irvine.

Consider lactose intolerance.

In the Jan. 14 issue of Nature Genetics, researchers at UCLA and in Finland reported the discovery of the genetic coding responsible for the inability of most adults worldwide to produce lactase, the enzyme needed to digest lactose in milk.

Nearly everyone makes enough lactase in infancy to digest breast milk. For many, though, the lactase gene switches off after weaning. From then on, the consumption of milk, ice cream and other dairy products can bring nausea, cramps, diarrhea, bloating or gas.

"It's easy to say it's not really a problem, but some people are suffering," said Leena Peltonen, UCLA chairwoman of human genetics and leader of the study. Worse, symptoms may mimic a serious digestive disease or cancer.

"That's why people are keen to get the diagnosis," she said. Identification of the gene for lactose intolerance means there one day will be an easy diagnostic blood test.

But Peltonen's team found something even more fascinating.

Same coding everywhere

In blood samples from 196 lactose-intolerant people of African, European and Asian descent, they found the same coding for the intolerance gene.

"If (a genetic feature) is found around the world, genetics tells us that it must be very old," Peltonen said. "Perhaps it was even in the genome of humans before they migrated out of Africa," that is, before modern humans differentiated into today's geographical "races."

So lactose intolerance isn't really a disorder; it's "normal," Peltonen said, and the ability to produce lactase into adulthood is a recent genetic mutation.

"My godson is lactose intolerant, and I told him, 'You are the original species, and all the others are mutants.' He really liked that," Peltonen said.

But the "mutants" must have enjoyed a survival advantage somewhere, or their ability to digest lactose never would have become as common as it is.

Such lactose "tolerance," it turns out, is most common among people of northern European descent. Seventy-five to 80 percent of them have no trouble with dairy products, compared with 10 to 25 percent of African and Asian populations.

The mutation may have been present in a few individuals everywhere. But Peltonen suggests it was in northern climes, with one harvest a year, where such people would have found a survival advantage in the year-round nutrition of cow, goat and sheep milk.

Another discovery reported last month may reveal an interplay of genetics with early human migration.

In the Jan. 8 issue of the Proceedings of the National Academy of Science, a team of U.S. and Chinese scientists reported evidence that a gene strongly associated with both attention-deficit hyperactivity disorder (ADHD) and "novelty-seeking" behavior resulted from a mutation only 10,000 to 40,000 years ago.

But what really caught the team's eye was that this gene — called the 7R allele — has spread rapidly among the world's population. It was "positively selective" because it gave its recipients a survival advantage.

But what advantage? The 7R allele is part of the dopamine neurotransmitter system involved in movement behavior, learning and responses to psychological rewards.

Kids with ADHD today have impulsive-behavior problems. They can't sit still and have difficulty concentrating in a classroom. People with the "novelty-seeking" trait are thrill-seekers. They frequently are mixed up with addictive drugs and alcohol.

The answers are still purely speculative. But Moyzis, the California biochemist and a member of the study team, said the timing of the 7R mutation coincided with a list of cultural innovations, and a restless surge of modern humans out of Africa and across the globe, displacing earlier populations.

"Perhaps individuals with personality traits such as novelty-seeking, perseverance, etc., drove the expansion," the study says. Moyzis noted that American Indians, whose ancestors pushed their wanderings the farthest, also have the highest incidence of ADHD.

"Whether it's good or not to have this gene may depend on the environment one finds oneself in," he said. "If you're in a society that requires you to go out and use your wits; to run around finding animals; if you're dealing with novel situations all the time — it might be good to have this gene."

On the other hand, he cautioned, it's also quite possible that it's not the ADHD traits at all that evolution has favored, but rather some other unidentified trait that's also linked to the 7R allele.

Exposing the hidden survival advantages in what appear to be genetic disorders is one of the most intriguing promises of evolutionary genetics.

Cystic fibrosis in Europe

For example, cystic fibrosis until recently killed most victims before they could reproduce. Yet evolution has conserved the CF gene and made CF the most common inherited disease among people of European descent. Why?

Statistically, Peltonen said, 25 percent of the children of two CF carriers will contract the disease. But 50 percent will inherit only one copy of the gene. They're spared the disease, and inherit instead a trait that slows the release of salts into the intestine. Scientists believe that may have saved them from severe dehydration and death from the diarrheal diseases that killed seven of 10 newborns in Medieval Europe. So the CF gene prospered.

Some researchers are investigating whether other common, genetically linked disorders such as autism, depression and schizophrenia also may have been positively selected because they confer hidden survival benefits.

"As long as whatever is being selected for is very positive, individuals are always going to be there that exhibit these negative things," Moyzis said.

Such research is "a new way of thinking about human genetics and biology," he said. "A lot of genetics has been too simplistic. It's going to turn out to be a little more complicated, with interactions between society and the expression of these genes."

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