The information encoded in your DNA determines your unique biological characteristics,
such as sex, eye color, age and Social Security number.

- Dave Barry
 

by Mark Pagel

Even detractors from the idea that genes are selected to maximise their own survival must grudgingly acknowledge beauty in the phenomenon of genomic imprinting.  Many genes vary their effects depending upon the environment in which they find themselves; for example, genes for antlers or long canine teeth are frequently silent in females.  Other genes spread to the detriment of their hosts.  But imprinted genes are altogether more subtle: an imprinted gene behaves differently depending on which parent contributed it to the offspring.  It knows whence it came, and the same gene acts one way if contributed by the father and another way if contributed by the mother.

The leading theory of imprinting proposes that mothers and fathers have conflicting interests in how much the mother should invest in their offspring: fathers wish to have mothers make large babies, mothers wish to spare some resources for future offspring.  Most known imprinted genes are involved with embryonic growth and fit neatly with this theory.  Steadily, however, evidence accumulates of imprinted genes that seem to have nothing to do with embryonic or other growth patterns.  A theory proposed by Iwasa, based on the principle of "dosage compensation," now provides an explanation for these observations.  It opens up a new theoretical domain to explain why imprinted genes may even affect social skills in boys and girls.

Offspring of sexually reproducing individuals have two copies of nearly all of their genes, one from the mother, the other from the father.  Normally both copies are expressed.  But imprinted genes carry some sort of a message - the gene may get tagged by methylation - which switches off one of the copies.  This same tag makes it possible to identify, and for the gene to behave as if it knows, its parentage.

A well-studied case is that of the Igf-2 gene, which produces an insulin-like growth factor that operates during embryonic development.  When this gene is expressed, demands are placed on the mother to provide more nutrients to the embryo.  In mice and humans, copies received from the mother are switched off, those from the father are not.  It is as if the otherwise identical maternal and paternal copies of the gene have adopted opposite and competing strategies that act to cancel each other in the developing embryo.

To explain this phenomenon, Moore and Haig proposed that during embryonic growth it might be in the paternally derived copy's interest to demand more of the mother than the maternally derived copy.  The reason?  If the mother is likely to produce children by more than one father, her offspring will be less related to each other than if the mother was monogamous.  A baby that under these circumstances places extreme demands on its mother may disadvantage her future offspring.  But these future offspring will be step-siblings and thus less likely to share genes than full siblings.  Confronted with this tactic, the maternal copy's best strategy is to switch off.  Monogamy is rare in animals, even in humans.  Of the 1,154 human societies documented in the Ethnographic Atlas, 1,073 practice some form of polygyny in which females may have children by more than one male.  Genomic conflict is one cost of infidelity.

Other embryonic growth genes show similar imprinting effects, and the conflict theory has received broad support.  But how can the conflict theory explain the observations of the powerful role that genomic imprinting plays in Turner's syndrome?  The X and y chromosomes are the sex-determining chromosomes in mammals.  Girls normally receive two X chromosomes, one from each parent.  Boys receive an X from their mother and a Y chromosome from their father.  Turner's syndrome arises when a girl receives only one X chromosome.  If it comes from the mother, the girl, among other things, is likely to be socially disruptive, behaviour that most parents will unhesitatingly recognise as normal in little boys.  If she receives her X chromosomes from the father, however, her behaviour is closer to normal for that of a girl.  Little girls indeed are Daddy's little girls.

It turns out that the X-chromosome genes associated with Turner's syndrome are imprinted.  The conflict theory, so successful with growth genes, cannot easily accommodate this.  The theory derived its force from the competing interests of mothers and fathers.  But, independently of how many different males a female has children by, there is no necessary conflict between mothers and fathers over sex differences in behaviour.  If what is good for a boy differs from what is good for a girl, then mothers and fathers will both wish to see these differences made manifest.

Iwasa's dosage-compensation explanation recognises that, because females have two X chromosomes and males only one, females potentially receive twice the dose of gene products found on the X.  This can be disruptive to other genes shared by males and females, and so females have evolved to switch off genes on one of their X chromosomes, and imprinting appears to be one way they do it.

If females, for whatever reasons, have been selected to have greater social skills than males, then that information must be contributed by the paternal X.  This is because the paternal X chromosome is always contributed to a daughter, but maternal X's can go to sons or daughters (Figure 1). Under these circumstances imprinting can evolve to provide a ready and precise mechanism for dosage compensation and, in this case, for paternal expression.

Figure 1:  A father's X chromosome always
contributes to a daughter's genetic make-up, the
mother's to a son's or a daughter's, meaning that
the paternal X chromosome can contribute
daughter-specific information on sex differences.
The theory proposed by lwasa is that genomic
imprinting may have evolved as a mechanism of
dosage compensation to silence the maternal X
or the paternal X as appropriate.

The same logic can be applied to understand the production of other sex differences by X-imprinted genes.  In mice, female embryos that lack one of the X chromosomes differ in size depending upon whether the missing chromosome is the paternal or maternal copy: those lacking the paternal copy are larger.  This is opposite to the pattern expected from the conflict theory.  In normal mice, females are smaller than males.  If the growth genes that produce this sex difference are carried on the X chromosome, then imprinting the paternally contributed copy to code for smaller size will produce the advantageous sex difference.  If it was the maternal copy that carried this information, daughters might be small, but so might be sons.

Despite setbacks, the conflict theory of imprinting can coexist peacefully with the dosage compensation/sex differences theory, as they explain different evolutionary settings.  Nevertheless, battles are certain to be fought over which theory applies in any given context.  In its favour, genomic-imprinting-based dosage compensation is a powerful and very general force that might be used whenever it is advantageous for sons and daughters to differ, be it in behaviour, morphology or physiology.  It also does not depend upon the existence or degree of polygyny, or any other factor that might pit mothers' and fathers' interests against each other.

Agreement between mothers and fathers, surprising as it may seem to evolutionary biologists brought up on conflict, may prove to extend even beyond dosage compensation and sex differences.  There is striking evidence that imprinting is involved in mammalian brain development, with the maternal copies of genes promoting growth of the cortex, while paternal copies retard it; the maternal genome may be responsible for at least part of the rapid expansion of the mammalian brain over evolutionary time.

No one knows why this pattern of gene expression has evolved.  One possibility is that, in a social species, it is advantageous for sons and daughters to inherit their mothers' brand or style of intelligence - after all, by virtue of surviving to reproduce she has shown that her cognitive style is suited to her environment.  Mothers and fathers can, in evolutionary terms, agree on this, and use imprinting to fine-tune genetic expression.  In the meantime, while these intriguing new phenomena are being investigated further, fathers can at least take heart that it is they who are to be credited for their daughters' exemplary social behaviour.

Mark Pagel is in the School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, UK e-mail: m.pagel@reading.ac.uk

Source: Nature Vol 397 7 January 1999

This article states that social skills for daughters are inherited from Dad.  The article on the following page (press the "Next" button below to view) goes even further and states that instinctual, emotional personality traits come primarily from the father.  Perhaps this explains many parent/child conflicts, especially in single-parent families.  If the mother and father split due to personality incompatibility, and, particularly in adolescence and young adulthood, their mutual daughter or daughters evidence the emotional and social traits of the father, the mother's accumulated negative responses to the ex-spouse could be discharged onto the offspring who evidence the same (disliked) behaviour traits.  (Ladies, pick your children's father with care!)  A man's sons would tend to have his wife's personality...

An article on an earlier page (see "Genetic Conflict") stresses the theory of genetic conflict rather than this theory of genetic agreement.

Paternal Feelings

Turner's syndrome affects 1 in 2,500 females and is characterised by short stature and the lack of sexual development at puberty.  Intelligence is usually normal, but the social adjustment of sufferers is frequently impaired.  Genetically, the syndrome is associated with partial or complete absence of one of the two female X chromosomes.  A comparison between 55 Turner's syndrome patients with a maternally derived X chromosome (45,XM) and 25 with a paternally derived X chromosome (45,XP) now shows that the 45,XP carriers have superior verbal and social skills and are better socially adjusted than the 45,XM carriers.  This suggests that the X chromosome carries an imprinted locus that bears a gene involved in cognitive function, normally expressed only from the paternal copy of the chromosome.  The existence of such a locus could explain why males, whose single X chromosome is maternally derived, are more vulnerable to some defects in social behaviour (such as autism) than females.

Source: Nature Vol 387 12 June 1997

Brains May "Jump" for Diversity

by Michael Schirber

Each of us has a unique head on our shoulders.  Although the basic hardwiring of the brain is the same, there are variances in shape and organisation that make even the brains of identical twins look different.  How much of this is due to environmental factors or genetic pre-programming has never been fully worked out.  But scientists have now found a connection between the variety in the brain’s neurons and certain genes that can change their position in the genetic code.  These so-called "jumping genes" may gently scramble the blueprints for the brain.  "This mobility adds an element of variety and flexibility to neurons in a real Darwinian sense of randomness and selection," said Fred Gage from the Salk Institute.

Jumping genes, also called transposons or mobile elements, are found in all living things.  Approximately 20% of the genetic code in mammals is of the jumping variety.  But only a small fraction of these are "active" - which means they are able to successfully reinsert themselves into a new spot in the code.  The fact that jumping is not easy to do is probably a good thing.  "You wouldn’t want that added element of individuality in your heart," Gage said.  But active jumping genes have been observed in sperm and egg cells - possibly providing a small kick to evolution by instilling tiny alterations to the genetic make-up of the next generation.

Gage and his colleagues tested a specific class of human jumping gene - called long interspersed nuclear element-1, or L1 for short - in cultured rat brain cells and genetically modified mice.  The experiments are detailed in this week’s issue of Nature.  What the scientists found is that L1 elements made hops in neuronal precursor cells (NPCs), which are cells that are destined to become neurons.  This is the first time these jumps had been observed in cells other than sperm and egg cells.  NPCs can turn into a variety of different neuron types - pyramidal and basket cells, to name just two.  If an L1 lands in the middle of an NPC gene associated with neural function, it could affect which type of neuron the NPC eventually becomes.  "What may happen is that when you are making a brain, there is a scattering of variability due to random shuffling by these jumping genes," Gage said.  But exactly how much of this shuffling goes on in human brains has yet to be studied.

In a separate commentary, Eric Ostertag and Haig Kazazian from the University of Pennsylvania point out that if jumping is entirely random, the L1 elements may rarely land inside a relevant gene.  There is some evidence, however, that the jumping genes actually target places in the code where they can make a difference.  Evolutionarily speaking, one might wonder how this remarkable hopping came into existence.  In most cases, a genetic mutation that provides a survival advantage eventually becomes incorporated in a population.  But these gene-altering jumps only affect how one brain develops and cannot be passed on to the next generation.  A possible answer to this Darwinian riddle is that there could be a definite advantage to a population in having programmed variability in the thinking caps of its members.

"If diversity was important, then the mechanism for creating diversity could be passed on," Kazazian said.

Source: livescience.com 15 June 2005

Adoptees Use DNA to Find Surname

DNA Molecule (SPL)
Tests read a number of genetic markers on the Y chromosome

by Paul Rincon

Male adoptees are using consumer DNA tests to predict the surnames carried by their biological fathers.  They are using the fact that men who share a surname sometimes have genetic likenesses too.  By searching DNA databases for other males with genetic markers matching their own, adoptees can check if these men also share a last name.  This can provide the likely surname of an adoptee's biological father.  The genetic similarities between men who share surnames occur on the Y chromosome, a package of genetic material passed on, more or less unchanged, from father to son - just like a last name.  Because of this pattern of inheritance, men with the same surname may also share a similar complement of genetic markers on the Y chromosome.

At least 30 men registered with US consumer genetic testing firm Family Tree DNA have found their "biological surname" in this way, the company's chief executive told BBC News.  The company has an online database called Ysearch containing genetic information from 125,000 men, along with surnames and other genealogical data.  Bennett Greenspan explained: "We now have a growing number of people who are adopted, who have tested with us and have matched several individuals with a particular surname, and maybe they haven't matched anyone else with a different surname.  From that, they can get the idea that they have at least found the surname they need to start looking for in the town in which they were born."

The tests can "read" up to 67 genetic markers on the Y chromosome.  Greenspan said that, for some adoptees, discovering the surname of their birth father in any other way might be extremely difficult, or even impossible.  "That's the real miracle of the DNA test.  [The Y chromosome] can act in a sense like a silver bullet." he said.

Mark Jobling, professor of genetics at the University of Leicester, UK, who is unconnected with Family Tree DNA said: "If you have a surname which is reasonably rare, but not so rare that the chances of another person being typed and going into that database are infinitesimal, then you could be in luck.  There's a big gamble in doing it, but people sometimes say that if you're in a dark room then even a little light can be useful."  Chandler Barber, a 37-year-old advertising copywriter from Dallas was adopted at birth; he said he had learned about the possibility of discovering his surname from a magazine article about consumer DNA testing.  Of 6 people in the Ysearch database who were close genetic matches, all had variants of the surname Ritchie, including one US-based Ruetschi who was a very close match.  "'It was pretty concrete evidence,' Mr Barber told me.  It's a quick and effortless way to at least find some nugget about your history.  I am sure there are people who have been searching for their birth parents on foot, with pen and paper, for years - and have got nowhere.  You start to wonder to yourself - 'If I do this, am I letting my family down?'  I told my mother: I really don't want to find my birth family.  I just want to know where I'm from.  But she told me that she had expected me to do this a long time ago."

Edward Cerullo, 48, a computer programmer from Norway, knew his birth father's surname - Page - before testing his DNA.  "When the results came back, of the 22 names they sent back who matched my DNA 11 were Page or Paige.  That's statistically pretty hard to argue against," he explained.  The database allowed him to see how his own line of descent fits into the wider family tree for this surname.

The link between last name and likeness on the Y chromosome gets stronger, the rarer the surname is.  But, said Mark Jobling: "Even in reasonably common surnames you see 'descent clusters'.  In a name like Jefferson, for example, which is quite a common name, you find lots of these little descent clusters.  There is identity within those clusters but there are many of them.  In a name like Attenborough, there is just one great descent cluster, and a few people who don't fit into it.  There's a spectacular common ancestry for that name."  But he cautioned that these general patterns might differ from country to country.  Also, some rare markers ran across two or more surnames, which might cause false matches.  Such false matches might also arise from technical issues with DNA databases.  For instance, genetic testing companies sometimes used different naming methods for genetic markers.  Confusion might arise when customers whose DNA had been tested by different companies uploaded their own genetic information into the same database.

Mark Jobling said tests offering better resolution on the whole genome should be able to solve other familial puzzles.  In the first half of the 20th Century, when a child was born out of wedlock, grandparents would sometimes raise the child as their own.  Professor Jobling said he knew of one man who suspected this had been the situation with his own immediate family.  An "older sister", this individual believed, had actually been his mother.  Unfortunately, the putative sister and parents were now deceased.  "If there is another relative, such as an acknowledged grandchild of this grandparental/parental couple, you can set up a hypothesis whereby you say: 'if they were his parents, how much of his DNA should he share with this cousin?'" the University of Leicester geneticist explained.  "If they were his grandparents, he should share a certain lesser proportion of his DNA with his cousin.  You can distinguish the two scenarios."

Professor Jobling said that falling costs of sequencing entire genomes offered the promise of finding genetic variants that were specific to one surname - with no room for ambiguity.

Paul.Rincon-INTERNET@bbc.co.uk

Source: news.bbc.co.uk  18 June 2008

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