Before efforts to sequence the human genome began, scientists thought they’d find about 100,000 protein coding genes in the three billion bases pairs of DNA that are found in almost every cell. But much to everyone’s surprise, the true number turned out to be much lower. It’s now thought that the human genome contains only about 20,000 protein-coding genes, representing less than 2% of the contents of the genome.

Much of the remaining 98% of the genome remains a mystery. Some chunks of this DNA are referred to as “ultraconserved elements” because they have remained practically unchanged through hundreds of millions of years of evolution in many species.

It is a basic principle of biology that if something goes unchanged for that long, it ought to be good for something. Yet the function of ultraconserved elements is completely unknown. In fact, laboratory studies in mice have shown that the animals do just fine when some of the ultraconserved elements are deleted.

To find out if ultraconserved elements really are dispensable, Cory McLean and Gill Bejerano of Stanford University analyzed ultraconserved elements and non-conserved DNA sequences in five mammalian genomes.

Their results, published online today in Genome Research, show that regions of DNA that are identical or very similar between humans, macaques, and dogs are about 300 times less likely to be missing in rats and mice than regions that are not as closely conserved between the primate and dog species.

It’s not that ultraconserved regions are somehow protected from change. The researchers suggest that in the wild, mutations in these elements put affected animals at a disadvantage, causing the changes to be swept away over time by natural selection. But in the lab there isn’t a whole lot of natural selection — in an environment where mice are treated to filtered air, an absence of predators, and all the food and water they could ever want, any loss of fitness due to lost ultraconserved elements doesn’t seem to have any observable consequences.

McLean and Bejerano also found that DNA sequences that can be traced farther back in evolutionary time are more likely to be conserved in diverse species today.

“The longer the sequence has been in us, the less likely it is to be lost. It’s almost like the bricks in the foundation of a building, which hold up the rest of the structure,” said Bejerano in a statement.

Detailed new genome sequences from a variety of mammals will allow Bejerano’s research team to further analyze ultraconserved elements and perhaps ultimately understand what it is they are doing in the genome.

“Evolution is a lot of fun,” said Bejerano. “You answer one question, and five others pop up. But one of the most rewarding things to me is the fact that we’re developing a growing appreciation for how much these regions actually matter.”

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Just four simple ingredients — water, malt, hops, and yeast – go into making beer, a delicious and intoxicating brew that has been enjoyed for the past 6000 years.

The yeast not only ferments sugars into alcohol, but also affects the appearance, aroma and taste of a beer. It’s not surprising then that each brewery maintains it own unique yeast strains. These strains, however, can be broken down into two main types: ale yeasts and lager yeasts.

It’s been known for some time that lager yeast is a genetic mix of yeast species S. cerevisiae (the same species ale yeasts hail from) and another species, S. bayanus. But the results of a new Stanford study that will be published online Thursday in Genome Research are the first to show that this mixing of DNA actually happened twice during the history of lager, and that the strain of S. cerevisiae involved was an ale yeast both times.

“We were excited to find this connection, because it makes so much sense,” said Gavin Sherlock,one of the study’s authors, in a statement. “The same breweries were used for both ale and lager, so it was really gratifying.”

Lager beers are brewed at much cooler temperatures than ales (52-58° F vs. 64-70° F), a tradition that dates back to Bavarian brewers who stored their beer in icy caves in the Alps during the summer months.

“It’s possible that the ale strain provides a certain flavor profile, while the second strain conferred the ability to ferment at cooler temperatures,” said Barbara Dunn, the other study author, referring to the hybridization events that created lager yeasts.

“Mixing them together is a nice way for the yeast to double its genetic options.”

When the researchers looked at yeast descended from the two groups of lager yeast, they saw further variation between strains.

“The fact that lager yeasts isolated from different breweries each seem to have a unique genomic make-up may indicate that the yeasts are adapting to the conditions specific to each brewery,” explained Dunn.

“Our discovery that unique genomic structures may be characteristic of each brewery and/or beer type could lead to insights on how to directly control flavor and aroma in beer.”

That’s the kind of science we can all raise a glass to.

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23andMe (in the form of Serge Saxonov and me, Brian Naughton) will be at the 7th Annual International Conference on Computational Systems Bioinformatics at Stanford this Tuesday. We will be giving a tutorial on some of the more technical and scientific aspects of 23andme’s service. It’s not all glitz and glamour, you know.

Serge and I will have a chance to talk about what’s going on under the hood of the Gene Journal (now called Health and Traits), Genome Explorer (now called Browse Raw Data), our many ancestry features, and of course, our new research effort, 23andWe.

23andMe is in good company at this year’s CSB, with other tutorials being given by Peter Karp from SRI, Mackenzie Cowell and Jim Morrison from MIT, Markus Covert from Stanford, Nader Pourmand from UCSC, and Jim Kent from UCSC. Come by if you have the chance!

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A Nilotic-speaking pastoralist from Tanzania / Sarah A. Tishkoff

Genes are just one component that children inherit from their parents. Throughout much of human history, especially when populations consisted of small hunter-gatherer groups, the language and lifestyle of a people were also inherited from generation to generation. This is why genetic patterns and cultural traits are often correlated. So, when scientists see cultural similarities between two populations, they can ask whether there are genetic similarities between the two groups as well. For many cultural traits, such as pastoralism and agriculture there is still a debate: did people actually migrate into new regions, bringing their genes and culture with them, or did the language and lifestyle simply spread by word of mouth to new lands?

In this week’s Proceedings of the National Academy of Sciences, scientists from Stanford University (several of whom are also associated with 23andMe, including myself) have used the principle of genetic and cultural exchange to find the first genetic evidence of a prehistoric migration of people from Tanzania to southern Africa. We discovered a mutation (aka ‘SNP’) on the Y-chromosome that originated about 10,000 years ago in eastern Africa and is now most common among people from two regions: Tanzania and southern Africa.

Pastoralists (people who rely heavily on animal husbandry for food) such as the Datog and Burunge of northern Tanzania carry the newly discovered SNP. In fact, it is present among 30-40% of men from these populations. Unexpectedly, the click-speaking Kxoe of southern Africa carry the same SNP at similar levels to the Tanzanian populations, indicating that these people are closely related to the Tanzanian pastoralists. The evidence indicates that men from southern and eastern Africa shared very recent common ancestors between about 1,200 and 2,700 years ago.

With this genetic evidence in hand, we then turned to archaeologists to see if the fossil record indicated an ancient migration around this time.

As it turns out, the current thinking among archaeologists is slightly different than what this new genetic evidence has revealed. Archaeologists currently favor a model in which the cultural practice of pastoralism spread from an unknown eastern African group into southern Africa about 2,000 years ago, perhaps without any sort of movement of people (i.e. genetic exchange). Our new genetic study, while still supporting the archaeological record for the timing and place of the origins of pastoralism in sub-Saharan Africa, puts a new twist on the current thinking. It suggests that a small group of men actually migrated into southern Africa about 2,000 years ago. These men probably married into local hunter-gatherer populations, contributing their livestock and cultural knowledge of pastoralism. These migrants were probably closely related to the modern day Datog and Burunge groups of Tanzania.

A shift to pastoralism was a fundamental change for the hunter-gatherers of southern Africa during the last couple thousand years. It caused a dramatic change in the culture and belief systems of these people. As pastoralism became more widespread in southern Africa, so did the beginnings of a sense of ownership of animals and the emergence of chieftans. These changes can still be seen today in the practices of people throughout Namibia, Botswana and South Africa. For example, the Nama of Namibia began practicing pastoralism not long after its arrival in southern Africa and continue to do so today.

The question of whether the shift from hunting and gathering to agriculture was the result of cultural exchange or actual migrations between groups is one of the most important debates among archaeologists and geneticists. With this new genetic evidence, we think we have answered this question, at least in southern Africa. Future studies will further examine the relationhip between genes and culture, and how this relationship has influenced the genetic and cultural makeup of modern African populations.

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