Wednesday, June 25, 2008

Human Evolution on Trial - Chromosomes and DNA - by Terry Toohill

Human Evolution on Trial - 'Chromosomes and DNA'



Most members of the jury will have heard of genes and know they are responsible for our inherited characteristics. As you probably already know, your genes control such things as your skin, hair and eye colour, the shape and size of your face, eyes and nose, your blood group and to a large extent your general height and shape as well as many other things, such as elements of your personality (Steve Jones 2000). One of my brothers believes even the willingness, or otherwise, of individual dairy cows to come into the open side of a herringbone milking shed is inherited. Anyway it is most likely that instinctive behaviour is genetically inherited in some way. Humans have many instincts. One of them is the ability to learn a language (Ridley 2000). We’ll come back to language periodically.


Humans may have up to a hundred thousand genes although the precise figure is debated. Some say many less than half this number but, almost certainly, the complex interrelationships between genes are usually underestimated. A change in a single gene can have a huge effect. For example cultivated maize differs from its vastly different wild form in just five genes (Jobling et al 2004). The environment we are brought up in does affect the influence of our genes, and some evidence indicates it may influence the genes themselves, but we can ignore both of these possibilities for now.


Experiments have shown that genes for each of your characteristics occur in pairs, one of each pair from your mother and your father. If the two genes of a pair are different usually only one of them gives rise to your observed characteristics. This one is called the “dominant” gene. The other one remains hidden but can be passed on to any of your offspring. This gene is called “recessive”. The evidence shows that your genes are carried on your chromosomes, which are confined to the nucleus (the centre) of each cell of your body. Except for the Y-chromosome, chromosomes usually occur in pairs. In fact the jury will see that a hierarchy of pairing passes on genetic information.


Y-chromosome


Each single chromosome, of each pair, consists of a double string of DNA (deoxyribonucleic acid) mixed with proteins. DNA is actually a string of what are called nucleotides attached to a series of alternating sugars and phosphoric acid (technically the nucleotide is the combination of all three chemicals). Just four types of nucleotides are present in the chain. In DNA they are adenine, thiamine, guanine and cytosine or A, T, G and C. Each strand of DNA is a string of up to a hundred million of these four nucleotides in various sequences giving a total of about three billion for the total human genome (see for example Stringer and McKie 1996). In the paired strand of nucleotides in each chromosome the adenine in one strand is always joined by hydrogen bonds to thiamine in the other, and guanine in one is joined to cytosine in the other strand (A-T, G-C). This means that chromosomes are easily able to replicate themselves. When the double strand of DNA splits each separate strand must replicate the other strand. Therefore the two new chromosomes, or double strands of DNA, are exactly the same as the original chromosome. The defence has included drawings of dividing strands of DNA in the genetic maps presented later (see for example map 2).


The main visible aspect of the function of DNA is the form we take as a developing foetus, our general shape and what type of creature we are. However in many parts of our body throughout our life DNA continually reproduces itself. This replaces our worn out tissue. But mistakes do occur and cancers can result.


In fact mistakes in the sequence of nucleotides in the DNA are reasonably common and are called mutations. Even identical twins have a few dozen differences in their total DNA (Cavalli-Sforza 1995). Harmless mutations in your reproductive cells are passed on to your descendants. These mutations lead to variation in the genetic makeup of individuals, and ultimately of different populations. In some cases it has been possible to work out the sequence in which such mutations have occurred. We’ll come back to this soon.


Apart from reproductive (sperm and egg) cells each cell of the human body has 46 chromosomes, made up of 23 pairs. Chromosome pair 23 is either a pair of X-chromosomes or a single X and a single Y chromosome. This determines whether you are female (XX) or male (XY). This is not true for all creatures. In birds and butterflies for example it is the female that has the equivalent of the XY combination.


Reproductive cells have only one of each pair of each chromosome, i.e. for humans 23 chromosomes including either a single X or a single Y. When fertilization occurs the normal condition of pairs is restored, one of each pair from each parent. Individual chromosomes are not passed unaltered from generation to generation though. Pieces can cross between the pairs of chromosomes during the formation of the reproductive cells. Because of this, genes from each parent can be thought of as mixing sort of randomly for the next generation. Gene linkages do occur, basically because genes close together on the chromosome are less likely to be separated (Jobling et al 2004). For example the genes for blond hair and blue eyes usually go together in humans, although they do show some independence.


During the formation of reproductive cells the pair of X-chromosomes in women behaves in much the same way as all the other pairs of chromosomes do, they mix. But, because there is no corresponding part on the X-chromosome for it to join with, most of the Y-chromosome is passed virtually unchanged from father to son. And virtually all genes on the single X-chromosome in men, which can come only from their mother, are expressed. This is why such things as baldness in men come through the mother’s side. Scientists have worked out the sequence of nucleotides in sections of what is called the non-recombining portion of the Y-chromosome (NRY). The differences reveal how closely related male members of different populations are. Scientists have constructed a family tree for the human Y-chromosome (“MtEve” [The Trees]). Large sections of it came from such witnesses for the defence as Hammer and Horai (1995), Karafet et al (1999), Underhill et al (2001) and Ke et al (2001). We are getting to know a great deal about migration of at least the male half of the human population. But we cannot automatically assume these movements always indicate population migrations that included women. It is not only married men who migrate to new regions. Any man who travels a lot can spread his genes, including his Y-chromosome, quite widely. For many reasons women’s genes usually spread more slowly.


Nuclear DNA


DNA is ultimately responsible (via RNA) for making proteins. Living matter is made up largely of protein. Matt Ridley (2000) writes “almost everything in the body, from hair to hormones, is either made of proteins or made by them”. Proteins are just long chains of amino acids. Twenty amino acids are commonly found in nature. Each amino acid is, in effect, coded for by a particular sequence of three nucleotides on the DNA. The pattern of nucleotides on the DNA therefore ensures a particular protein always has the same sequence of amino acids; but any mutation in the DNA can change some aspect of the protein it is responsible for and even the creature itself. It has been shown statistically most mutations seem not to have any effect though (Lewin 1999).


Any harmful protein change would usually be eliminated during foetal development, or possibly even before conception. Mutations that provide an advantage for any individual with it are probably very few and far between. Harmless protein changes move slowly through a population, as individuals with the mutation move around and leave descendants. But particular mutations are usually concentrated in particular geographical regions. The book “History and Geography of Human Genes” by Cavalli-Sforza et al (1994) can provide many hours of contemplation. It contains about 500 maps of the distribution through the world of various genetically controlled blood proteins and enzymes. Further processing of this data by a system called “principal component analysis” has provided maps of mutations that tend to occur together in clumps. The map of the first principal component for each region shows the distribution of the greatest level of genetic variation within that region.

Because, by definition, the maps pick up only genes that display regional variation the two opposite extremes are usually each concentrated in separate regions, but they merge gradually into each other. Once the regional genetic combination that makes up the first principal component is removed the next most common one (second principal component) is revealed, often showing a completely different pattern, and so on.

Studying these maps gives us an indication of the migration of different human populations around the world and the defence will call on Cavalli-Sforza’s maps many times as evidence in favour of the defendant. Of course humans, like all species, share the vast majority of their genes with each other. That is why we all look roughly the same but this case will concentrate mainly on those genes that vary within each species and group of species.


Although DNA evidence is readily accepted in Courts of Law to establish close relationships or the identity of individuals it does seem as though many of us are unwilling to accept DNA evidence of relationships in the present case. Of course the same mutation at the same point on the DNA molecule in two different individuals at different times may lead to our misinterpretation of the evidence in some cases.


So at conception you received genes from each parent in the ratio of 50:50. Some research suggests that the egg is able to select the best sperm, but the selection of genes from each parent is basically random. So when you were conceived you took half your genes from your father and half from your mother which, mixed together, make up your characteristics.


Dominant and Recessive Genes


Each of your genes provides two possibilities, one from your mother and one from your father. Any gene always expressed as a characteristic is called the dominant gene. By convention the dominant gene is written with a capital letter, e.g. “B”. The lower case letter, “b”, is used for the recessive (the one that usually doesn’t show). Because each individual has two genes for each characteristic the only possible combinations are “BB”, “Bb”, “bB” and “bb”. You can put the gene from your mother or your father first but be consistent. It sometimes makes a difference whether the gene comes from the mother or the father (Jones 2000). The reasons for this are complex and needn’t concern us. “BB” and “bb” are called “homozygous” (the same gene on each chromosome) and “Bb” and “bB” are called “heterozygous” (different gene on each chromosome).


Dominance can actually be complete or incomplete. In the case of complete dominance the first three examples above would all look the same for that characteristic. Just the one individual in four with the combination “bb” would look different. In cattle the black colour is dominant. In that case “B” could represent a dominant gene for the colour black and “b” represent a recessive gene for the colour white. The combination “bb” would be the only one that would produce a white animal. The other combinations would all be black.


A particular gene always occurs at a particular section of a chromosome. In each individual only two options are available because they have pairs of chromosomes, one of each pair from each parent. But in the population as a whole there may be many different genes available for that place. Human blood groups, for example, have three options on the chromosome: A, B and O.

Four blood groups exist: O, A, B or AB. O is recessive and so always homozygous (oo) but A and B can be homozygous (AA and BB) or heterozygous with O (Ao and Bo). AB is an example of incomplete dominance. This is what makes us all so different. And in the case of the B and b example a gene for a reddish-brown colour could be available as well as genes for black or white. This complicates things but dominance may still be complete. Black may be dominant over both red and white, and red dominant over white for example.


Some genes are co-dominant or cumulative: the heterozygous “Bb” or “bB” can be sort of halfway between the homozygous “BB” and “bb”. For the example of black and white given above the heterozygous individuals would be some shade of grey. With the addition of the red gene a combination of red and black could give a dark brown or bay colour, and red and white a fawn or dun colour. In some cases heterozygous individuals (“Bb” or “bB”) are actually at an advantage over either homozygous extreme. This is one of the things that ensure “hybrid vigour” or “heterosis”. In practice, though, characteristics that vary along a continuum between two extremes are usually the product of several different pairs of genes at different places even on different chromosomes, which individually demonstrate complete dominance.


In actual fact black is not the dominant colour in all animals. For example white is dominant in cats. In this particular case the gene that gives rise to the white also leads to deafness and white cats, especially males, are usually deaf (Jones 2000). This means there has been what is called “selection” against white cats, otherwise all cats would be white (I would bet there has also been selection against white cats for other reasons as well. Except in snow a white cat is easier to see when it is hunting or being hunted for instance).


The concept of selection has been borrowed from farming. Farmers control which individuals in their dairy herd, for example, will be able to leave more genes in the form of descendants. They do this by “selecting” which animals to either breed from or get rid of. In effect nature does much the same thing with animals and plants. If individuals with a particular characteristic are less successful at breeding those without the characteristic will make up the population numbers. This is called natural selection.


Selection keeps disadvantageous mutations at a low level. But if a dominant gene appears in a population it obviously spreads very rapidly through the generations if individuals with it leave more offspring that in turn leave more offspring etc. A recessive gene spreads more slowly because selection can operate only on individuals where the gene is expressed, i.e. those born with a double recessive. If individuals with a double recessive leave more offspring after many generations the whole population will have become double recessive. The dominant gene will then be extinct. By that time another advantageous recessive may have arisen in the population at the same point on the chromosome. In this way a recessive gene can become dominant but not, of course, over any gene it had previously been recessive to. The defence will expand on this in “Hybrid vigour and Inbreeding” [Wave Theory of Evolution].


And I’m afraid it is not really even that simple. Many animals have genes that make the two colours paler, appear in patches, stripes or spots on their bodies, and some even have three colours. Calico, or tortoiseshell, cats for example can have three colours. Most genes for colour in cats happen to be carried on the X-chromosome. To get a tortoiseshell and white cat there has to be a red gene on one X-chromosome and a black gene on the other X-chromosome as well as other genes that promote patching with white. Because males have only one X-chromosome tortoiseshell cats are usually female. Any males that are tortoiseshell-coloured must have an extra X-chromosome and they are sterile.


Genetic information therefore is carried in a way that allows an almost infinite variety of possibilities. A number of genes are available for each point on the chromosome and a number of points on the chromosome can carry similar genes. There are also genes responsible for switching on or off other genes. In fact most characteristics are almost certainly the result of a series of such genes (Ridley 2000). For any characteristic there is a sort of hierarchy of genes. Whether a gene is dominant or incompletely dominant is probably also ultimately under genetic control.


For practical purposes we can regard populations, or whole species, as being simply collections of genes, or nuclear DNA, in various proportions. The study of this is called population genetics and the defence will use information gained from studying cattle to explain the idea many times during this case. Because a great deal of information is available for cattle they are ideal for the study of practical genetics. Not only have desirable qualities been bred for; the change each generation can actually be measured.

Meat quality, weight and growth rates for beef cattle progeny can be measured accurately. In dairy cows milk production, protein and fat percentage in the milk, overall size, temperament, teat placement and udder shape are all to some extent genetically controlled and can be measured, or at least subjectively judged. All these individual traits have what is called a bell curve distribution. As you move away from the most common type in any direction numbers fall off in the shape of a bell. The further from the majority you get the fewer individuals there are. The jury will eventually understand how we can see that in effect each individual gene travels through a population on its own independent wave.


My grandfather milked Shorthorn and Red Devon cattle breeds. By the time my uncles took over the farm Jersey cattle had become the fashion. But they didn’t need to buy a whole new herd. They just formed a sequence of hybrids with Jersey bulls. After three cow generations the herd was ⅞ Jersey (“Pedigrees” [Ancestry]). They looked like Jerseys but when I was a child some cattle in the herd still had pink noses or were brindled, a throwback to the earlier breeds. Their fathers had Shorthorn or Red Devon ancestry too.


When Friesian cattle then became popular it was again possible to gain a Friesian herd by the same method. But the mitochondrial DNA of many Friesian cows in the New Zealand dairy herd goes right back to Shorthorn or Red Devon cattle.


Mitochondrial DNA


So far we have been dealing with nuclear DNA, the DNA responsible for your genes. But there is another type of DNA in your body. It is called mitochondrial DNA (mtDNA). This DNA is not involved with the formation of genes (Jones 2001) and it occurs as a circular molecule (the ends are connected). Human mitochondria each consist of just sixteen and a half thousand pairs of the nucleotides: A, T, G and C. Each cell of the human body may have up to ten thousand molecules of mtDNA but most have far fewer. Mitochondria occur outside the nucleus and are known as the powerhouse of the cell.

They produce the proteins responsible for digestion within the cell. These proteins are involved in the production of ATP (adenosinetriphosphate) from various acids produced in the body. This process takes up oxygen and produces carbon dioxide and water. In the vast majority of individuals all the mitochondria in every cell have exactly the same DNA but mutations do occur. If the mutation happens in an egg cell it is passed on to the offspring.


The egg cell needs its mitochondria for metabolism and cell division but the sperm’s mtDNA is effectively discarded and lost at fertilization (Jobling et al 2004). Therefore the mtDNA is passed unchanged from only the mother to the child for thousands of generations. In fact the mtDNA does change over time (mutations). The rate of this change and the regularity of the change have been greatly debated by scientists; i.e. does it have a sort of half-life? How much does it change, say, in a thousand years? Is the change totally random or does selection act on these changes? It is now generally accepted that some sections of mtDNA change quite rapidly and regularly, and it has been shown that one parent-child comparison in forty has a mitochondrial mutation (Jones 2000). Because there is a great deal of mtDNA in each individual, and it is a relatively short chain, it has been the easiest DNA to extract and to study.


Like the Y-chromosome, the sequence of the nucleotides in sections of the mtDNA has been worked out for individuals of many species. The accumulation of differences in the sequences can be used to indicate the relationship of various groups of animals and humans through their mother’s ancestry. If the mtDNA is only a little different it is presumed they are closely related and of course this would be so, no matter what the rate of mutation.


Again, like the Y-chromosome, examination of the mutations in human mtDNA has been used to construct an evolutionary, or family, tree. From this it has been concluded we all descend from a single woman who lived in Africa. We will meet her again and see her family tree in “MtEve” [The Trees]. But before then the defenve needs to explain a few more things.


Studies of the changes in mitochondrial DNA and the Y-chromosome have been very useful in helping us understand our origin but we need to consider other evidence before we jump to conclusions. The first thing we need to consider, and explain, is the present distribution of human genetic variations.


See next :: Human Evolution On Trial - 'The Human Star'


Witnesses Called



Cavalli-Sforza, Luigi Luca, Menozzi, Paolo and Piazzi, Alberto (1994) The History and Geography of Human Genes. Princeton University Press, New Jersey.

Cavalli-Sforza, Luigi Luca and Cavalli-Sforza, Francesco (1995) The Great Human Diasporas. Addison- Wesley

Hammer, Michael F. and Horai, Satoshi (1995) Y Chromosomal DNA Variation and the Peopling of Japan. Am. J. Hum. Genet. 56: 951-962

Jobling et al (2004) Human Evolutionary Genetics. Garland Science, New York.

Jones, Martin (2001) The Molecule Hunt. The Penguin Press, London.

Jones, Steve (2000) Almost Like a Whale. Anchor, London.

Karafet et al (1999) Ancestral Asian Source(s) of New World Y-chromosome Founder Haplotypes. Am. J. Hum. Genet. 64: 817-831.

Ke et al (2001) African Origin of Modern Humans in East Asia. Science Vol. 292 1151-1152

Lewin, Roger (1999) Patterns in Evolution. Scientific American Library, New York.

Ridley, Matt (2000) Genome. Harper Collins, New York.

Stringer, Christopher and McKie, Robin (1996) African Exodus. Random House, UK.

Underhill et al (2001) Y-Chromosome Haplotypes and Implications for Human History in the Pacific. (pdf) Human Mutation 17: 271-280.

3 comments:

Tim said...

Hi Terry - re:

"Humans have many instincts. One of them is the ability to learn a language (Ridley 2000). We’ll come back to language periodically"

I wonder at what point in human evolution people became multi-lingual.

terryt said...

This is simply my guess, based on my perception of how evolution in general works. I've touched on the subject a little in the essay "Culture". I would guess that, like evolution in general, if we could somehow look at every detail of language evolution, we would have a great deal of difficulty defining exactly when language first evolved.

The many genes involved would have to spread through the population over generations. Simple language at first (whatever that means) and basic genes. But languages would therefore have been diversified right since they first developed. But, like genes including Y-chromosome and mtDNA haplogroups, they are altered or even replaced as new ones are introduced. (Of course you can't just "alter" a population's Y-chromosome and mtDNA haplogroups. They're either totally or partially replaced).

terryt said...

The next essay in the series is "The Human Star":

http://remotecentral.blogspot.com/search/label/Human%20Evolution%20On%20Trial%20-%20Human%20Star

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