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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.
<h6>Ultraconserved Elements</h6>
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 <a href="http://biology.plosjournals.org/perlserv/?request=get-document&#038;doi=10.1371/journal.pbio.0050234&#038;ct=1" target="_blank" rel="noopener noreferrer">do just fine</a> when some of the ultraconserved elements are deleted.
<h6>Humans and Macaques</h6>
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 <a href="https://genome.cshlp.org/cgi/content/abstract/gr.080184.108v1" target="_blank" rel="noopener noreferrer">Genome Research</a>, 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.
<h6>What it might mean</h6>
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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23andMe Blog Team

The Mystery of Ultraconserved Elements

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What is it about humans that distinguishes us from the rest of the animal kingdom?   Is it our upright walking?   Our language?   Our love of Reality TV?   Even though we are said to be 99% genetically identical to our closest evolutionary relative, the chimpanzee, we clearly differ vastly from them physically and behaviorally.
For many years, scientists have attempted to understand how our species came to be so different from any other on the planet.   In the October issue of <a id="ikcg" title="Nature Reviews Genetics" href="https://www.nature.com/nrg/journal/v9/n10/abs/nrg2428.html" target="_blank" rel="noopener noreferrer">Nature Reviews Genetics</a>, scientists at the UCLA and the Howard Hughes Medical Institute examine recent research to understand how genetic mutations have set us apart from our nearest relatives. In addition, they discuss how these genetic changes relate to the vast array of physical and behavioral differences that also have to be considered to fully understand what makes our species so unique.
<h6> 
The 1% Difference</h6>
The authors begin their examination of human uniqueness by focusing on the overall genetic differences between our species and chimpanzees.   Many years ago, research revealed that humans and chimpanzees are remarkably similar in terms of both genetic and biochemical structure.   Scientists hypothesized that because the two species are so structurally similar, the differences between humans and chimps would turn out to be primarily in the way that genes — and therefore proteins — are expressed.   Further analysis confirmed that there is only a 1% difference in overall genetic and biochemical structure between the two species – a number many people still cite today.
However, the authors argue that more recent analysis has actually shown that deletions and duplications of DNA in both species bring the genetic difference between the two to about 4% across the entire genome.   These and other findings have, according to the authors, “dashed the hope that it would be simple to determine the key genetic differences between humans and closest evolutionary relatives, that is, the genomic aspects of ‘what makes us human’ ”.
Yet many recent breakthroughs in comparative genomics have identified human genetic features that may be unique.   Below are two examples:
<h6>MYH16</h6>
One key difference between humans and chimpanzees is the difference in brain size.   Humans have an average brain volume of about 1500 cm3, which is roughly three times the size of a chimp&#8217;s.   While having a comparatively large brain was one of the most important factors in the evolution of our species, it has also resulted in an organ that is very expensive to maintain.   In fact, many anthropologists have argued that in order for our large brains to have evolved, there must have been a simultaneous reduction in the size of other organ systems and muscle mass.
In 2004, scientists discovered a gene, MYH16 that may have been involved in that trade-off between increased brain size and decreased muscle mass.   Believed to be related to the growth of muscles in the jaw of chimpanzees and other apes, MYH16 has been mutated in humans so it remains switched off.   Scientists hypothesize that the gene&#8217;s lack of expression in humans causes an eight-fold reduction in the size of muscle fibers in the human jaw.   Interestingly, the timing of this mutation appears to have happened about 2 million years ago, when Homo erectus — the first of our fossil ancestors to exhibit a significant increase in brain size, evolved in Africa.
<h6>FOXP2</h6>
Sometimes referred to as &#8220;the language gene,&#8221; FOXP2 made a splash in the popular media when it was first described in 2002, because a very slight mutation in the human version is believed by some to have led to the evolution of language in humans.
FOXP2 is not unique to humans.   In fact, many species — including songbirds and alligators — have the gene, which is required for proper brain development.   Though the human FOXP2 gene is slightly different, it has been found to be related to vocal learning in birds, and may even be tied to the evolution of echolocation in bats.
In addition, new research has suggested that it may not be the FOXP2 gene itself, but rather a related genetic pathway, and it is that related gene that may be involved in the evolution of speech and language development in humans.   At the moment the exact relationship between FOXP2 and human language remains unresolved – an illustration of the genome&#8217;s complexity.
<h6>Genotype vs. Phenotype</h6>
The authors conclude their review by proposing a method of examining human uniqueness from a genomic perspective in light of the fact that “traditional evolutionary biology approaches have yet to explain most of the unique features of humans.”   They argue that in order to move the field of evolutionary genomics forward, and to truly understand what it means to be ‘human,’ there must be more of an effort to connect changes at the genetic level (our genotype) to changes at the physical level (our phenotype).   Interestingly, questions of the relationship between genotype and phenotype form the cornerstone of 23andMe’s research arm, <a id="t3pm" title="23andWe" href="https://www.23andme.com/research/" target="_blank" rel="noopener noreferrer">23andWe</a>.
Finally, the authors argue that it will take scientists from a variety of disciplines — developmental biology, genetics, anthropology, anatomy, sociology, and many others — to fully examine the myriad of ways in which humans are set apart from our closest relatives.   It is at this point, the authors conclude, that we will fully understand what it means to be ‘human.’

What it Means to be Human

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An animal&#8217;s ability to survive often depends on how well it can avoid predators.   Many species of fish, birds, and mammals have evolved ingenious methods of staying hidden from predators by blending into the background in one form or another.   But what about animals that do the opposite?   How and why would such attention-grabbing features as a lion’s mane, a male deer’s antlers, or a peacock’s tail evolve?   As it turns out, these traits can be explained by something called sexual selection.   Sexual selection is an aspect of evolutionary theory developed by Charles Darwin in the 19th century after he began to notice many traits that were exaggerated, especially among the male members of the species.   Darwin reasoned that within a species, there must be a &#8220;struggle between the individuals of one sex, generally the males, for the possession of the other sex.&#8221;   So in the same way that women may prefer men with broad shoulders, female peacocks prefer their male counterparts to have ornate feathers — the larger the better. Evolutionary biologists have understood the concept of sexual selection for years, but there has been much debate over how this process occurs at the genetic level.   For example, male and female lions have basically the same set of genes. So how are these genes modified such that male lions develop a mane while females do not?   The answer, as it turns out, is surprisingly simple.
 In this week’s issue of Cell, molecular biologists tackled the question of how sexual selection works by examining the genetics of fruit flies. Male fruit flies have evolved a unique coloring pattern on their abdomens that apparently attracts females in the same way that a peacock’s feathers do.   Females lack the markings, yet they have basically the same genome males do. So how is it that the same basic genome (aside from sex chromosomes) can lead males and females to develop different physical traits? According to University of Wisonsin-Madison biologist Sean Carroll, &#8220;The flies did not need new genes … they just changed how males and females use a common set of genes.&#8221; Carroll and his team discovered that while both male and female fruit flies have the genes necessary to create the abdominal coloring pattern, it is only the males who have that gene switched on.   In female fruit flies, this gene lies dormant. “With this particular trait, it evolved by exploiting (genetic) information that was already there to make male bodies different from female bodies,’ explains Carroll. So how does the genetics of a coloring pattern on fruit fly abdomens apply to sexual selection in other species?   According to Carroll and his colleagues, the same genetic mechanisms that are at play in the fruit fly also operate in a multitude of other animals — including lions, deer, peacocks, and even humans.   This study, in showing the genetic means for how sexual selection may operate, illustrates the ingenuity of evolution — how a seemingly simple genetic switch can create such beautiful and elaborate features in the male members of thousands of the world’s species.

Is That a Peacock Feather under your Coat … Or are You Just Happy to See Me?

The question: What does DNA look like?
While many of the 23andMe scientists have purified DNA more times than we’d like to remember, there are a fair number of people here (on the science team and on the engineering and business teams) who’ve never spent any time at the lab bench. We love all things DNA around here, so we recently set out to make sure everyone at 23andMe has gotten up close and personal with some Gs, Cs, Ts, and As.
We didn’t use human DNA — instead we isolated the genetic material of strawberries (click here for instructions). It’s pretty simple: smash up some strawberries with some soap and salt, add some rubbing alcohol, and voila! DNA!
As you can see in the pictures and video below, it’s an activity that is fun for all ages!
[minislides]
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The Answer: Snot

Editor&#8217;s Note: This post does not reflect our current product offering. 23andMe&#8217;s ancestry product looks at the autosomes (chromosomes 1-22), the sex chromosomes (XY), and mitochondrial DNA (mtDNA). For more information about how results are different for men and women go here.
One of the most exciting parts of 23andMe’s <img decoding="async" class="right alignright" src="https://blog-api.23andme.com/wp-content/uploads/2008/05/gus.jpg" alt="gus.jpg">
<h6>Paternal vs. Maternal</h6>
At present, 23andMe customers can trace two branches of their genetic family tree — one that follows the all-female line on the maternal side (through mitochondrial DNA) and another the all-male line on the paternal side (through the Y chromosome).
Not all DNA is created equal, however: males have both mitochondrial DNA AND a Y chromosome, so they can trace both their maternal and paternal ancestry. Females, who have mitochondrial DNA but no Y chromosome, can trace only their maternal ancestry.
So how can females discover their paternal history? One solution is to ‘borrow’ the Y chromosome of her most immediate paternal ancestor — her father. A female can have her father send his own DNA sample to 23andMe, then examine his Y chromosome as a way of understanding his paternal ancestry and her own.
<h6>Discovering Paternal Ancestry</h6>
But what if a woman&#8217;s father can&#8217;t or won&#8217;t share his DNA? By sharing 23andMe accounts with the right male relative, a woman can still discover both her maternal and paternal ancestry.
So whose DNA can a female customer use, besides her father&#8217;s? It could be anyone who shares his Y chromosome — her brother, paternal uncle (father’s brother), or even paternal grandfather (father’s father). The chart below illustrates some of the possibilities in one woman&#8217;s family tree; male relatives who share her father&#8217;s Y chromosome are depicted in blue.
You may look at the chart and ask: Why not her son’s Y? After all, he&#8217;s a male relative, too. But even though a mother shares 50% of her genes with each of her children, only fathers pass Y chromosomes to their sons. So any examination of her son’s Y chromosome would yield not her father&#8217;s paternal history, but her husband&#8217;s.
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The woman whose family tree is shown here (&#8220;Me&#8221;) could determine her paternal ancestry using the Y chromosomes of males who are colored blue.

Whose Y to Use? Paternal Ancestry for Ladies

It’s a question we’re getting used to: “Why are you called 23andMe?”
Many of you know the answer by now: our name refers to the 23 pairs of chromosomes usually found in humans.
But a question you may not know the answer to is “Why do humans have 23 pairs of chromosomes? Why not 13? Or 27?”
Well, it would take a while to trace the history of each of our chromosomes. But the tale of how we got down to 23 pairs from the 24 of the common ancestor we share with chimpanzees, our closest relatives in the animal kingdom, is pretty straightforward — and pretty cool.

A few million years ago after the final evolutionary split between man and chimp, two chromosomes fused. In humans, two chromosomes came together end to end, creating our chromosome 2.
The fusion of two chromosomes wasn’t particularly unusual — throughout evolution chromosomes have been breaking apart and joining together in new combinations. Many of our chromosomes can be shown to be rearranged versions of chromosomes found in other animals.
Scientists can “paint” chromosomes using fluorescent probes that detect specific DNA sequences. When they paint the DNA of a human cell with probes that detect human chromosome 2 sequences, they see one pair, as expected. But if the same probes are used in a chimp cell, two pairs of chromosomes light up, showing us chromosomes 2’s parents.
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Chromosome 2 painting in a human cell, right, and an orangutan cell, left (which has 24 chromosomes like a chimp). Stefan Mueller, Department Biologie II der Ludwig-Maximilians-Universitie Muenchen.
Check out <a href="https://www.23andme.com/gen101/genes/" target="_blank" rel="noopener noreferrer">Genetics 101</a> for more info on chromosomes and the numbers found in other species.

How’d We Get 23?

If you think mutations are just sinister events that create human flies and gigantic man-eating ants, you live in a &#8217;50s B-movie. Though they sometimes cause significant problems for the organisms who acquire or inherit them, mutations are actually the engine of evolution. Without them, life as we know it could not exist.
In this week&#8217;s installment of &#8220;The Wild Side,&#8221; her weekly column in the New York Times, evolutionary biologist Olivia Judson explains that there are many kinds of mutations. Some affect the parts of genes that encode proteins, the molecules that do most of the work in a biological organism. By changing the structure of these functional molecules, these mutations can dramatically affect an organism&#8217;s appearance, metabolism, or behavior. Mutations in the protein-coding region of the MC1R gene, for example, influence skin, hair, coat, and feather color in humans, mice, and birds.

Other mutations affect genome regions that determine where, when or how much of a protein is produced. These regulatory mutations can cause effects just as dramatic as the functional ones that alter protein structures. For example, a mutation in a genetic switch that controls the LCT gene allows many people — usually those from cultures where raw milk is a regular part of the diet — to digest the milk sugar lactose as adults. Until relatively recently in human (pre)history, that gene was always turned off after infancy. In most of the world&#8217;s people, it still is today.
It will take decades of research to understand how these regulatory mutations influence our biology; Judson guesses they play a major role in differentiating us from other species. And closer to the mission of 23andMe, they probably play a big role in differentiating us from one another as well.
So next time you hear the word &#8220;mutation,&#8221; don&#8217;t think of three-eyed fire-breathing lizard men — think of yourself.
Illustration by Derek Grime/istockphoto.

23andMe and You — Page 13