Category Archives: Genetics

Neolithic Revolution in the air!

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THE NEOLITHIC REVOLUTION WAS A KEY MOMENT IN THE PREHISTORY OF HUMANS. It sparked civilisation as we know it- settlements were established, crops were grown and animals were domesticated transforming the economy of subsistence globally. Beginning in the Levant (Near East) around 12,000 years ago, the Neolithic Revolution spread into Europe 8000 years ago and lasted up until 4000 years ago when the Bronze Age began.

The major question is how did this revolution spread? Did the indigenous hunter gatherers adopt farming solely though cultural transmission? Or did the farmers pass on their practices alongside their genes? These two models (see diagram) – culturally diffused model (CDM) and demic diffused model (DDM) – originally seen as two polar opposites as mechanisms of the spread, have been debated throughout the 20th century. By identifying the proportion of Mesolithic/ hunter-gatherer and Neolithic/ farmer genes within the current gene pool (see diagram), the correct model could be identified.

Classical genetic markers in present day populations (such as blood groups) appear to lend support to the DDM revealing a genetic cline from the Near East towards the West. But modern genetic markers can reflect population processes that have taken place both before and after the Neolithic spread. Instead ancient DNA (aDNA) provides a unique window of opportunity to look back into the past. Ancient DNA studies do come fraught with difficulties. Over time DNA degrades and fragments into short molecules. Usually this means any contaminating modern DNA is favourably extracted and analysed instead. Nevertheless strict and rigorous protocols exist to minimise contamination and new technology has been optimised for aDNA extraction.

The archaeological record has shown that as farmers migrated across Europe, two different routes were taken as indicated by distinct ceramic styles. One route was through Central Europe, from Hungary to Slovakia, Ukraine and through to Paris, as shown by the Linearbandkeramik (LBK) and Alföldi Vonaldiszes Kerámia (AVK) pottery styles. The other route represented with Impressed Ware/Cardial culture was along the Mediterranean coast. aDNA studies have been conducted on samples from these different sites and cultures, and the picture that emerges is one more complex than just picking one model over the other. It certainly appears that the two routes have their own model: while the Central Europe/ LBK route shows little to no genetic continuity between the Mesolithic hunter-gatherers and the Neolithic farmers, the Mediterranean route tends towards genetic continuity and therefore a level of gene flow between the two populations, a pattern which even seems to lead up into Sweden.

But this most certainly is not the end of the story. For one thing, the genetic studies carried out were analysing the mitochondrial DNA (mtDNA), which is inherited solely down the female line (men inherit their mothers’ mitochondrial DNA but will not pass it on). In one study, it was found that of Spainish Neolithic samples while the mtDNA belonged to hunter gatherer groups from the Palaeolithic, the Y chromosome was shown to be from the Neolithic Near East. This does seem to suggest that the role of men and women during the advance of the Neolithic differed to some extent. Additionally, it also appears that the change to farming practices did not happen as rapidly as expected, and was not as clear cut. In two recent papers (with a particular focus on Germany), it was found that hunter gatherers and farmers lived alongside each other for about 2000 years and, interestingly while the Mesolithic hunter gatherers and the Neolithic farmers had their own distinctive gene pools, at some point in the Neolithic there were intermediary groups with shared ancestry and lifestyle undoubtedly reflecting the transition that was taking place.

There is a level of difficulty when studying the past; we cannot always state processes or cause and effects with a perfect degree of certainty, but we can say what the evidence appears to suggest, and in this case it appears to suggest a high a degree of complexity as the Neolithic Revolution took hold. There is never just any one specific model that can answer our questions, and there will always be other lines of evidence to explore. To answer the original question how the Neolithic Revolution spread cannot be placated with just one simple answer. It is never that easy. But as aDNA analyses show, we can still get one step closer to that very complicated answer.

More information:

Bollongino et al 2013 Science 342 (6157) 479-481

Brandt et al 2013 Science 342 (6155) 257-261

Gamba et al 2011 Molecular Ecology 21 (1) 45-56

Haak et al 2005 Science 310 (5750) 1016-1018

Lacan et al 2011 PNAS 108 (45) 18255–18259

Pinhasi et al 2012 Trends in Genetics 28 (10) 496-505

Skoglund et al 2012 Science 336 (6080) 466-469Neolithic Revolution

 

 

 

Reproduction Revamp: Stick Insects and Going It Alone.

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Timema cristinae: making a lack of a love life cool.

Love can be tough. If you wish awkward dates and trawling through match.com were a thing of the past, you could take a leaf out of this stick insect’s book. Tanja Schwander (University of Lausanne) studies how Timema stick insects are changing the dating game. Rather than reproducing with a partner, female Timema have developed the ability to produce offspring individually.  There could be a number of causes for this bizarre transition from sexual to non-sexual offspring production, so read on for a how-to guide in ditching dating.

Conversion to non-sexual reproduction may occur genetically. When female Timema are prevented from mating, some eggs that haven’t been fertilised by sperm hatch and develop. Could this virgin birth scenario, reminiscent of biblical times, replace sexual reproduction in Timema? Or are virgin births merely a strategy to ensure female stick insects can carry on their line when opportunities to mate are thin on the ground?

Alternatively, a type of bacterial infection may stimulate non-sexual reproduction. Infecting bacteria are only transmitted through the female sex cell, the egg, and so males slow the spread of the bacteria. In light of this, the bacteria devised a cunning strategy to eliminate males: inducing a kind of non-sexual reproduction that produces only female offspring. Could bacterial infection be the instigator of non-sexual reproduction?

Schwander’s studies of genetic data reveal the virgin birth scenario cannot explain the change in Timema reproduction. Conversion to non-sexual reproduction may occur genetically, but not via virgin births. To determine if bacterial infection causes the stick insect’s lack of libido, Schwander cured the infection. This restored sexual reproduction and production of male offspring, proving bacterial infection can result in non-sexual reproduction. Watch this space; could Boots’ next bestseller be bacteria to eliminate human males?

Designer Babies- What’s It All About?

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Throughout the social and scientific worlds, there is controversy surrounding the potential to genetically modify embryos to create ‘designer babies’. These are embryos that have been screened for genetic diseases, and will therefore only contain selected desired qualities chosen by the parents. However, there are many stories in the media which exaggerate and distort the facts- and this can even be seen in the term ‘designer babies’ itself. It is important to think about the likelihood and implications of this idea, plus to outline what actually gave rise to this concept.

We could suggest that the idea of genetically engineered embryos or the ideas that led to this originated in 1978 and the first in-vitro fertilisation (IVF) treatment. The procedure gave and still gives hundreds of infertile couples a chance to have a child by transferring an egg fertilised in a laboratory into the mothers uterus. It subsequently led to a procedure known as preimplantation genetic diagnosis (PGD). This is a technique used on embryos to profile their genome- it is a form of genetic profiling and embryo screening and is a more technical and accurate way of regarding ‘designer babies’. In terms of health benefits, using PGD means embryos can be screened outside the womb. Embryos can be selected that only carry normal and healthy genes, and are therefore free from genetic abnormalities. Whilst this technique is currently popular, PGD could in the future be used to select any desired specified trait of a child, such as eye colour, intelligence, and athleticism; be used to select embryos to be without a genetic disorder, to increase successful pregnancies, to match a sibling in order to be a donor, for sex selection and therefore be used to design your own baby. Selecting the gender of a child is already possible due to the fact only the X or Y chromosome needs to be identified, but other traits are more difficult due to the amount of genetic material required. Recent breakthroughs have meant that every single chromosome in an embryo can be scanned for genes involved in anything from Down’s Syndrome to lactose intolerance using a single microchip, but how advanced is this and what are the ethics behind this?

There are a large array of ethical, social and scientific concerns over the concept of creating a ‘perfect’ child. Some people worry that in the future there will be an imbalance between genders in the general population especially in societies that favor boys over girls, such as China. Also, a key issue suggested is that there is an element of eugenics to this idea- PGD will mean that people with ‘unattractive’ qualities will be lessened and potentially society may discriminate against those who have not been treated. If we look at this from a more extreme perspective, it could be suggested that we may end up with a race of ‘super-humans’ and a divide between those who have been treated and those who haven’t.  Also, this selection of genotypes suggests a potential deleterious effect on the human gene pool, meaning less genetic variation. Whilst at first this may seem positive due to the fact you could eliminate genetic disorders such as hemophilia A before it becomes prevalent in the body, it is also likely that new diseases may evolve and accidentally be introduced into the human race. Due to the decreased gene pool, only partial evolution would be able to occur and therefore we will be more susceptible to new diseases having a dramatic effect. It is clear from this evidence that regulations must be put in place and strictly enforced before any new advances are made.

So, how close are we to being able to ‘customise’ our children?
In terms of altering genes already present in the embryo, we are already well on our way to refining this technology. Scientists have been altering animal genes for years, and germline therapy is already being used on animals. Germline gene therapy is now being closely linked and developed with PGD- and it could soon be used to change human genetics. Our germline cells are our sex cells (egg and sperm), and using this branch of gene therapy essentially involves manipulating and adding new genes to the cells. The clear possibility from this in terms of PGD is that any trait can be added to an embryo to create a designer baby. This may involve adding a gene to stop a genetic disorder being expressed in a baby’s phenotype by fixing them as they are noticed in PGD, but it could also mean that only certain people will be able to advance in society.

On he other hand however, before these ‘more advanced’ humans are created we need to learn more about the genetic code. The basis of all genetic technologies lies in the human genome, and whilst PGD advances are ever-increasing, at present we can only use this technique to look at one or two genes at a time. Therefore, we cannot use it to alter the genes in embryos, and this would logically lead us to think about gene therapy, but the current lack of technology and the strict regulations regarding experimenting with germline gene therapy makes it unlikely that anyone will be able to create a completely designer baby in the near future.

Designing our babies is a reality that government bodies and various organizations are beginning to accept and address fully, and society’s view of the moral implications behind PGD and gene therapy being a key factor in determining how far this concept can advance; there will be increasingly new debates and controversy over the acceptable applications of gene technologies in humans and human embryos.

 

 

 

 

 

Biotech for all – taking science back to it’s roots?

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This morning I came across a very interesting TED talk by Ellen Jorgensen entitled “Biohacking — you can do it, too” (http://on.ted.com/gaqM). The basic premise is to make biotech accessible to all, by setting up community labs, where anyone can learn to genetically engineer an organism, or sequence a genome. This might seem like a very risky venture from an ethical point of view, but actually she makes a good argument for the project being at least as ethically sound than your average lab. With the worldwide community of ‘biohackers’ having agreed not only to abide by all local laws and regulations, but drawing up its own code of ethics.

So what potential does this movement have as a whole? One thing it’s unlikely to lead to is bioterrorism, an idea that the media like to infer when they report on the project. The biohacker labs don’t have access to pathogens, and it’s very difficult to make a harmless microbe into a malicious one without access to at least the protein coding DNA of a pathogen. Unfortunately, the example she gives of what biohacking *has* done is rather frivolous, with a story of how a German man identified the dog that had been fouling in his street by DNA testing. However, she does give other examples of how the labs could be used, from discovering your ancestry to creating a yeast biosensor. This rings of another biotech project called iGem (igem.org), where teams of undergraduate students work over the summer to create some sort of functional biotech (sensors are a popular option) from a list of ‘biological parts’.

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The Cambridge 2010 iGem team made a range of colours of bioluminescent (glowing!) E.coli as part of their project.

My view is that Jorgensen’s biohacker project might actually have some potential to do great things. Professional scientists in the present day do important work, but are often limited by bureaucracy and funding issues – making it very difficult to do science for the sake of science. Every grant proposal has to have a clear benefit for humanity, or in the private sector for the company’s wallet, which isn’t really how science works. The scientists of times gone by were often rich and curious people, who made discoveries by tinkering and questioning the world around them, and even if they did have a particular aim in mind they weren’t constricted to that by the agendas of companies and funding bodies. Biohacking seems to bring the best of both worlds, a space with safety regulations and a moral code that allows anyone to do science for whatever off-the-wall or seemingly inconsequential project that takes their fancy – taking science back to the age of freedom and curiosity.

A matter of inheritance

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Image courtesy of 'Digital Dreams' / FreeDigitalPhotos.net

Image courtesy of ‘Digital Dreams’ / FreeDigitalPhotos.net

The age-old ‘nature-nurture’ debate revolves around understanding to what extent various traits within a population are determined by biological or environmental factors. In this context ‘traits’ can include not only aspects of personality, but also physical differences (e.g. eye colour) and differences in the vulnerability to disease. Investigating the nature-nurture question is important because it can help us appreciate the extent to which biological and social interventions can affect things like disease vulnerabilities, and other traits that significantly affect life outcomes (e.g. intelligence). The ‘nurture’ part of this topic can be dealt with to some extent by research in disciplines such as Sociology and Psychology. In contrast genetic research is crucial to understanding the ‘nature’ part of the equation. Genetics also has relevance for the ‘nurture’ part of the debate because environmental factors such as stress and nutrition affect how genes perform their function (gene expression). Indeed genetic and environmental factors can interact in more complex ways; certain genetic traits can alter the probability of an organism experiencing certain environmental factors. For example a genetic trait towards a ‘sweet tooth’ is likely to increase the chances of the organism experiencing a high-sugar diet!

Given the importance of genetic information to understanding how organisms differ, I would argue that a basic knowledge of Genetics is essential for anyone interested in ‘life sciences’. This is true whether your interest is largely medical, psychological or social.  Unfortunately if, like me, you skipped A-Level Biology for something more exciting (or A-Level Physics in my case!) you might Genetics at bit of mystery.

Some basic genetics

Genetic information is encoded in DNA (Deoxyribonucleic acid). Sections of DNA that perform specific, separable functions are called Genes. Genes are the units of genetic information that can be inherited from generation to generation. Most Genes are arranged on long stretches of DNA called chromosomes, although a small proportion of genes are transmitted via cell mitochondria instead. Most organisms inherit 2 sets of chromosomes, one from each parent. Different genes perform different functions, mostly involving the creation of particular chemicals, often proteins, which influence how the organism develops.  All cells in the body contain the DNA for all genes, however only a subset of genes will be ‘expressed’ (i.e. perform their function) in each cell. This variation in gene expression between cells allows the fixed (albeit very large) number of genes to generate a vast number of different chemicals. This in turn allows organisms to vary widely in form while still sharing very similar genetic information (thus explaining how it can be that we share 98% of our DNA with monkeys, and 50% with bananas!).

The complete set of genetic information an individual has is called their ‘genotype’. The genotype varies between all individuals (apart from identical twins) and thus defines the biological differences between us. In contrast the ‘phenotype’ is the complete set of observable properties that can be assigned to an organism. Genetics tries to understand the relationship between the genotype and a particular individual phenotype (trait). For example how does the genetic information contained in our DNA (genotype) influence our eye colour (phenotype)? As already mentioned environmental factors play a significant role in altering the phenotype produced by a particular genotype. Explicitly the phenotype is the result of the expression of the genotype in a particular environment.

Heritability

Roughly speaking, heritability is the influence that a person’s genetic inheritance has on their phenotype. More officially it is the proportion of the total variance in a trait within a population that can be attributable to genetic effects. It tells you how much of the variation between individuals can be attributed to genetic differences. Note that this is not the same as saying that 60% of an individual’s trait is determined by genetic information. In narrow-sense heritability (the most common form used), what counts as ‘genetic effects’ is only that which is directly determined from the genetic information past on by the parents. This ignores variations caused by the interaction between different genes, and between genes and the environment. This is the most popular usage of heritability in science because it is far more predictive of breeding outcomes, and therefore tells us more about nature part of the ‘nature-nurture’ question, than the alternative (broad-sense) conceptualisation of heritability.

Uses and abuses

Genetic research can provide crucial information in the fight against certain diseases. Identifying genes that are predictive of various illnesses allow us to identify individuals who are vulnerable to a disease. This then allows preventive measures to be implemented to counter the possible appearance of the disease. Furthermore once the genes that contribute to a disease are known, knowledge as to how those genes express will help reveal the cellular mechanisms behind the disease. This improves our understanding of how the disease progresses and operates, and therefore helps with identifying treatment opportunities. In reality of course Genetics is rarely this simple. Many conditions that have a genetic basis (i.e. that show a significant level of heritability) appear to be influenced by mutations within a large number of different genes. Indeed in many cases, especially with psychiatric disorders, it may be that conditions we treat as one unitary disorder are in fact a multitude of different genetic disorders that have very similar phenotypes. Nevertheless, despite these problems genetic research is helping to uncover the biological basis of many illnesses.

One problem with Genetics, and heritability in particular, is that of interpretation. There is often a mistaken belief that a high level of heritability signifies that environmental factors have little or no effect on a trait. This misunderstanding springs from an ignorance of the fact that estimates of heritability comes from within a particular population, in a particular environment. If you change the environment (or indeed the population) then the heritability level will change. This is because gene expression is affected by environmental factors and so the influence of genetic information on a trait will always be dependent to some extent on the environment. As an example a recent study showing that intelligence was highly heritable (1) lead to some right-wing commentators using it as ‘proof’ of the intellectual inferiority of certain populations, because of their lower scores on IQ tests. Such an interpretation is then used to argue that policies relating to equal treatment of people are flawed, because some people are ‘naturally’ better. Apart from the debatable logic of the argument itself, the actual interpretation of the genetic finding is flawed because a high heritability of IQ does not suggest that environmental differences have no effect on IQ scores. To illustrate this point consider that the study in question estimated heritability in an exclusive Caucasian sample from countries with universal access to education. If you expanded the sample to include those who did not have access to education it would most likely reduce the estimate of heritability, as you would have increased the influence of environmental factors within the population being studied! Ironically therefore you could argue that only by treating everyone equally would you be able to determine those who are truly stronger on a particular trait! Independent of what your views on equality are, the most important lesson as regards genetics is that you cannot use estimates of heritability, however high, to suggest that differences in the environment have no effect on trait outcomes.

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 References

(1) Davies, G. et al (2011) Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Molecular Psychiatry 16, 996-1005. http://www.nature.com/mp/journal/v16/n10/full/mp201185a.html

Although not directly cited, I found the following information useful when creating the post (and when trying to get my head around Genetics!).

Quantitative Genetics: measuring heritability. In Genetics and Human Behaviour: the ethical context. Nuffield Council on Bioethics. 2002.  http://www.nuffieldbioethics.org/sites/default/files/files/Genetics%20and%20behaviour%20Chapter%204%20-%20Quantitative%20genetics.pdf

Visscher, P.M., Hill, W.G. & Wray, N.R. (2008) Heritability in the genomics era – concepts and misconceptions. Nature Reviews Genetics, 9 255-266. http://www.ncbi.nlm.nih.gov/pubmed/18319743

Bargmann, C.I. & Gilliam, T.C. (2012) Genes & Behaviour (Kandel, E.R. et al (Eds)). In Principles of Neural Science (Fifth Edition). McGraw-Hill.

Dominant and Recessive Genes In Humans

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As briefly referred to in the previous Genetics blog, for each of our genes we posess two ‘alleles’. One of these alleles in inherited from our father and one from our mother. There can be many different alleles for one gene and it can be completely up to chance, or perhaps luck, what we inherit from our parents. When speaking in general terms about dominant and recessive alleles, we tend to speak about genes as if for each of them there are two different alleles. This is not always, or often, the case, but it sometimes is and makes it much easier to explain this way.

For example, for a particular gene, say the ability to roll your tongue, there is a dominant and a recessive gene. We can call the dominant allele ‘R’ for being able to roll our tongue and the recessive allele ‘r’ for being unable to roll our tongue. Our parents could posess any combination of these alleles: AA, aa or Aa. Then, it is completely down to chance what we inherit from them.

One unexpected example is that the allele for dwarfism in humans is the dominant allele and the allele for normal growth is recessive. This means that if we inherited both of the different alleles for this gene we would show the dwarfism trait.

Below is a table of dominant and recessive traits shown in humans.

Dominant Trait in Humans

Recessive Trait in Humans

A blood type

O blood type

Abundant body hair

Little body hair

Astigmatism

Normal vision

B blood type

O blood type

Baldness (in male)

Not bald

Broad lips

Thin lips

Broad nose

Narrow nose

Dwarfism

Normal growth

Hazel or green eyes

Blue or gray eyes

High blood pressure

Normal blood pressure

Large eyes

Small eyes

Migraine

Normal

Mongolian Fold

No fold in eyes

Nearsightedness

Normal vision

Rh factor (+)

No factor (Rh -)

Second toe longest

First or big toe longest

Short stature

Tall stature

Six fingers

Five fingers normal

Webbed fingers

Normal fingers

Tone deafness

Normal tone hearing

White hair streak

Normal hair coloring

 

When we are speaking about the inheritance of alleles and the genetic make-up of a person with respect to one gene, we use one of two phrases. The first is homozygous, meaning that the two alleles an individual posesses for one gene are the same i.e. AA or aa. The second is heterozygous, meaning that the two alleles an individual posesses for one gene are different i.e. Aa.

By Robyn Bradbury

Finding out what makes you, you.

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Although Genetics is often seen as just another jigsaw piece making up the wide subject of Biology, it really underlies the whole study.

After all, is the most fundamental question of life not how does the set of chemicals inside us provide our every essence? How are those chemicals changed from simple molecules to everything that makes up a human being?

One thing which makes Genetics so interesting is that not even the best geneticists in the world can fully answer these questions. It is still a science very much in its infancy and early stages of understanding. After all, it was only around sixty years ago that James Watson and Francis Crick made the discovery of the structure of the DNA double helix. What is most fascinating about how these men made their discovery is that they came to their final theory of the double helix without any experiments of their own; they simply brought together other people’s evidence and used it to their advantage to gain their own final answer.

The less molecular side of Genetics which most people have heard something of is that of Gregor Mendel’s pea plant experiments: he performed genetic crosses with the plants, noting parent and offspring characteristics. As far back as 1856, he laid the foundations of what remain the basic principles of Genetics in these modern times. Mendel introduced the theory of recessive and dominant characteristics, without fully understanding what he was proposing.

A gene, in simplified terms, is a stretch of DNA coding for a characteristic in an organism. Allele is the word used when there are two or more different forms of a gene, so there can be different alleles for a particular gene. These different alleles can be classed as recessive or dominant, which basically do as their names suggest i.e. genes come in stronger or weaker forms; dominant being stronger and recessive being weaker. This means that one allele can dominate over the other and if both alleles occur, the so-called dominant allele will be shown. Since we have two copies of every gene, one from our mother and one from our father, any allele combination can occur. Therefore for a gene with two alleles, A (dominant) and a (recessive), there are three different allele couplets which could occur: AA, Aa or aa. This is called the organism’s genotype, the genes contained within its cells. The organism’s genotype produces a particular phenotype, which is the characteristic shown by an organism due to its genotype. For instance, in Mendel’s pea plant experiment, he found that yellow colour is dominant to green colour in the peas – yellow colour could be shown by the allele Y and green colour can be shown by the allele y. This means that in this case, the pea plant can have the genotypes of YY or Yy which will show a yellow phenotype, or yy which will show a green phenotype.