It's not just the genes...

Increasingly we are realizing that it isn't just the genes that are important but how those genes are expressed.

This was nicely illustrated in a Science paper this week where they looked at the role of the Agouti gene in pattern development: The Developmental Role of Agouti in Color Pattern Evolution.

Agouti, ... governs color patterns in deer mice, the most widespread mammal in North America. This gene, found in all vertebrates, may establish color pattern in a wide variety of species, a process that has been poorly understood at both the molecular and the evolutionary level.

Agouti had previously been known to affect the type of pigment found in vertebrate fur, feathers, and scales: Little expression of the gene in adults results in the production of dark pigments, while robust Agouti activity generally yields light pigment production. But Manceau and Hoekstra found that subtle changes in the gene's embryonic activity can also make a profound difference in the distribution of pigments across the entire body.

"During embryogenesis, Agouti is expressed in the belly, where it delays maturation of the cells that will eventually produce pigments," says Hoekstra, John L. Loeb Associate Professor of the Natural Sciences at Harvard. "This leads to a lighter colored belly in adults, which is the most common color pattern across a wide variety of vertebrates, from fish to antelope."

Even small changes in Agouti gene expression can establish a completely new color pattern. In deer mice, natural selection drives changes in the amount and place of Agouti expression, which in turn results in new color patterns that can camouflage animals from visual predators in habitats including dark forests and light sandy beaches.

"It is hard not to speculate that Agouti plays a role in generating more complex patterns -- from stripes to spots -- in a diversity of vertebrates," Hoekstra says.
 

 Looking for a picture of a leopard to add I found this cool picture of a black panther (panthers are just black leopards). Notice how you can see the pattern of spots in the fur even though the fur is all black.

Haplodiploidy

Haplodiploidy is a  mechanism of sex determination that is common in the hymenoptera but also found in some other groups. In this system sex is determined by the number of sets of chromosomes an offspring receives. Fertlized eggs develop as females, and unfertilized eggs develop as males. This means that the males have half the number of chromosomes that a female have - hence the name haplodiploidy for this system. In this system males have no father and cannot have sons, but have grandfathers and can have grandsons (think about it). Also because males are already haploid all the sperm they produce is identical.

Haplodiploidy has important consequences that seem to affect social behavior. Here's a nice description form an online Animal Behavior textbook:

1. If a queen mates only once, her daughters are highly related to each other (called supersisters), because the father's sperm are all identical.
2. A female is more related to her sisters (on average, 75% similar) than she is to her own daughters (on average 50% similar).
3. A female is more related to her son (50 % similar) than she is to a brother (on average, 25% similar).

These three factors combine to create a condition in which it may be more advantageous, evolutionarily speaking, for a female to help her mother produce sisters (to the female in question) than to produce her own daughters. Thus haplodiploidy opens the way for the evolution of a worker caste, devoted to helping their mother. If workers evolve under these conditions, then we would expect:

• That all workers will be female (males have no special pattern of relatedness in a haplodiploid system that would make working advantageous to them
• That workers will help their mother to lay and rear females, but
• That workers would prefer to lay their own male offspring, rather than rear brothers

In fact, Hymenoptera workers are uniformly female and conflict between the queen and the workers over who lays the males eggs in a nest is common. The role of haplodiploidy in the evolution of worker Hymenoptera fits into an overall theory of how genetic similarity affects social behavior called kin selection which was developed by Bill Hamilton.

Red Heads

Are red heads going extinct? When this question was asked, I dove further as I have a 2 year old son who has red hair even though no one, as far back as we can trace, on his father's side nor mine, has red hair. I found this article particularly interesting because it led to another question of whether the feisty behavior can be linked to the same gene as the pigment in the red hair...? Any thoughts?

Heterozygote advantage

At this point it's fairly clear that heterozygote advantage is not going to be a major force in the maintenance of genetic diversity simply because we've found so few examples. Perhaps not surprisingly with our rapidly expanding knowledge of genetics and gene function someone has now found some examples of heterozygote advantage that don't involve partial resistance to a disease. I missed this paper in PLoS ONE a few years ago:

Heterozygote Advantage for Fecundity
Heterozygote advantage, or overdominance, remains a popular and persuasive explanation for the maintenance of genetic variation in natural populations in the face of selection. However, despite being first proposed more than 80 years ago, there remain few examples that fit the criteria for heterozygote advantage, all of which are associated with disease resistance and are maintained only in the presence of disease or other gene-by-environment interaction. Here we report five new examples of heterozygote advantage, based around polymorphisms in the BMP15 and GDF9 genes that affect female fecundity in domesticated sheep and are not reliant on disease for their maintenance.

Are blondes/redheads dying out?

In 2002 there was a series of stories in the press announcing that blondes were dying out. A typical story from the BBC:
Blondes 'to die out in 200 years'.
The proposed mechanism for this loss of blondes was simply that the gene was recessive

..too few people now carry the gene for blondes to last beyond the next two centuries.   The problem is that blonde hair is caused by a recessive gene.

But, as we saw today, Hardy and Weinberg cleared that up for us over 100 years ago. An allele will not decline in frequency simply because it is recessive.


The story appeared to originate with the World Health Organization, although suspiciously, no scientists were named. It subsequently turned out the whole story was dubious if not fake. The WHO eventually issued a press release: 

''W.H.O. has no knowledge of how these news reports originated,'' said the organization, an agency of the United Nations based in Geneva, ''but would like to stress that we have no opinion of the future existence of blonds.''

Because news stories tend to have a cyclical life of their own this story has resurfaced a number of times since 2002.

Skip forward a few years  to 2005 and a series of press reports on a similar fate for redheads:
Gingers extinct in 100 years, say scientists
This time the story can be chased back to a misreporting of a story in National Geographic and the 'Oxford Hair Foundation' - funded by a manufacturer of hair dye.

Haploinsufficiency

I hope that some of you got to attend Carol Greider's talks on Friday, or the meet and greet on Saturday. I went to the talk on Friday afternoon and was very impressed, not only was the science very impressive (well duh) but she also gave a great talk that I thought was pitched just right for the audience.

She also used a word that I immediately realized I should know and, fortunately, was fairly self explanatory - haploinsufficiency -

Haploinsufficiency occurs when a diploid organism only has a single functional copy of a gene (with the other copy inactivated by mutation) and the single functional copy of the gene does not produce enough of a gene product to bring about a wild-type condition. Haploinsufficiency is therefore an example of incomplete or partial dominance.
 
Production of telomerase within a cell appears to be an example of haploinsufficiency.

The most interesting part of the talk was at the end when the link between the evolution of insufficient production of telomerase (and therefore diseases of aging) and the dangers of too much telomerase and cancer became clear.

Mendelian inheritance

It is known that Mendel ordered 40 reprints of the paper that described the results of his now classic experiments, "Experiments on plant hybrids" published in the transactions of the Natural History Society of Brünn in 1866.

He sent these out to scientists he thought would be interested (possibly including Darwin). Only a single scientist responded and, unfortunately he steered Mendel completely wrong.

Karl (or Carl) von Nägeli, of the University of Munich, had previously experimented with hawkweed, a plant that follows an obscure asexual reproductive method. Mendel started experimenting with hawkweed, and began to question his findings from studying peas. He finally gave up all experimentation when he became abbot of the monastery, though he continued to dabble in ornamental horticulture.

Although very few of these 40 reprints survive, in a strange story last year Mendel's original manuscript has surfaced and has become the subject of an inheritance dispute (seriously): A Family Feud Over Mendel’s Manuscript on the Laws of Heredity

Tricky question

This is a question from one of the major biology textbooks. I've always felt questions like this one to be right on the borderline between being a trick question and not. What do you think? Fair question? I'll post a comment on what the answer is NOT.

Karen and Steve each have a sibling with sickle-cell disease. Neither Karen nor Steve nor any of their parents have the disease, and none of them have been tested to reveal the sickle-cell trait. Based on this incomplete information, calculate the probability that if this couple has a child, the child will have sickle-cell disease.

Epigenetics again

As I very briefly mentioned today epigenetics is a very exciting and new area of biology. About a year ago this topic was so hot and sexy it hot the cover of Time magazine. The article, Why Your DNA Isn't Your Destiny, is really rather good. I'm personally always interested in how journalists try to tell science stories.

All this explains why the scientific community is so nervously excited about epigenetics. In his forthcoming book The Genius in All of Us: Why Everything You've Been Told About Genetics, Talent and IQ Is Wrong, science writer David Shenk says epigenetics is helping usher in a "new paradigm" that "reveals how bankrupt the phrase 'nature versus nurture' really is." He calls epigenetics "perhaps the most important discovery in the science of heredity since the gene." 

I think the coming years will make it clearer to what extent epigenetics is really going to revolutionize our thinking about heredity or whether it is going to become a collection of rather unusual, but not typical, processes.

Here's a previous post on epigenetics that links to some primary research, some of it carried out here at UCSB in David Low's lab. David is affiliated with CCS and  has had very positive interactions with CCS students in his lab so there's definitely one possibility for research if this area of research interests you.

Siamese cats

The coat pattern in Siamese cats is a form of partial albinism, resulting from a mutation in tyrosinase, an enzyme involved in melanin production. The mutated enzyme is heat-sensitive; it fails to work at normal body temperatures, but becomes active in cooler areas of the skin. This results in dark colouration in the coolest parts of the cat's body, including the extremities and the face, which is cooled by the passage of air through the sinuses.

Many early Siamese were cross-eyed to compensate for the abnormal uncrossed wiring of the optic chiasm, which is produced by the same albino allele that produces coloured points. However the crossed eyes have been seen as a fault and through selective breeding, the trait is far less common today.

Details of the Tyrosinase mutation are available in this 2006 paper: Albinism in the domestic cat (Felis catus) is associated with a tyrosinase (TYR) mutation

Genetics problem

Karen and Steve each have a sibling with sickle-cell disease. Neither Karen nor Steve nor any of their parents have the disease, and none of them have been tested to reveal the sickle-cell trait. Based on this incomplete information, calculate the probability that if this couple has a child, the child will have sickle-cell disease.

I'll post a comment about what the answer is not. See what answer you get first.

From Gene Flow to Genetic Pollution

Maize field grown in one of the 15 communities known to be contaminated by genetic pollution spread over 3 states of Mexico. From Greenpeace.org

The seemingly innocent concept of gene flow, the movement of alleles from one population to another, has become a bit of a hot topic in environmental circles since the author Jeremy Rifkin used the term 'Genetic Pollution' in 1998 to describe undesirable gene flow into wild populations. Although this often refers to the flow from genetically modified organisms to wild populations, conservation biologists have also used it to describe the undesirable flow of genes from any captive population to wild populations (eg from salmon in fish farms to local salmon populations).

Greenpeace, for example, have a page specifically about genetic pollution. Yet some people question the use of this term

"If you take a term used quite frequently these days, the term “genetic pollution,” otherwise referred to as genetic contamination, it is a propaganda term, not a technical or scientific term. Pollution and contamination are both value judgments. By using the word “genetic” it gives the public the impression that they are talking about something scientific or technical--as if there were such a thing as genes that amount to pollution.

They use it in terms of GM and in their anti-salmon farming and anti-aquaculture campaigns. If, for example, a fish escapes from a farm and interbreeds with a wild fish of the same species, they call that genetic pollution. They don’t realize that what they are saying in terms of science would be the same thing as saying that if a white person married a Chinese person, that would be genetic pollution."

What's Wrong with the Environmental Movement: an interview with Patrick Moore Competitive Enterprise Institute staff, Environment News 2004 published by The Heartland Institute.

It's an interesting discussion that makes you think about the way that words are used and abused.

Scientists in Japan clone mice that had been frozen for 16 years

http://www.reuters.com/article/newsOne/idUSTRE4A26NV20081103

They suggest this leads to the possibility of cloning extinct species from the cells of frozen animals like mammoths. I've also heard the idea that being able to clone animals could lead to an ethical meat option for vegans and vegetarians (no animal would be harmed as the meat would be grown by itself in a lab).