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Are human beings still evolving?

{Note: this lecture is based on many sources, some of which are quoted directly alongside the slides. Ask for specific sources if you need them: dyec@who.int.} If this picture (David Driskell, Spirits Watching) does not stimulate thoughts about human evolution, the next few certainly will.

Slide 2

Charles Darwin's 200th birthday was on February 12th, and it's been just over 150 years since the seminal papers of Darwin and Wallace were read at the Linnean Society in Piccadilly (ranked #1 among Time Out's top 100 London moments). Darwin's most famous and (still to a few) controversial book is "On the Origin of Species…", but he later summoned up courage to publish "The Descent of Man", an account of human evolution, which discussed "whether man, like every other species, is descended from some pre-existing form; the manner of his development; and the value of the differences between the so-called races of man." The controversy surrounding the "Origin" led to Darwin being lampooned as the product of his own argument.

Slide 3

Evidence as to Man's Place in Nature TH Huxley 1863

And prominent contemporaries lined up for and against Darwin's theory. His principal champion, Thomas Huxley, included this picture in his 1863 "Evidence as to Man's Place in Nature", made famous by endless parody.

Slide 4

Here are a few of them, none of them very optimistic (mostly from www.uv.es/jgpausas/he.htm).

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Slide 7

A simplified version of this picture appears in the cover of the book "El Mono Obeso" by JE Campillo.

Slide 8

From www.steinbergforcongress.com.

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Slide 9

Some imagine that there is an ultimate life form. This in itself is flawed evolutionary thinking. This particular idea about the ultimate life form is especially erroneous?

Slide 10

And last but not least, women on top, the most chilling interpretation (to at least half the audience). Woman are all that's needed (biologically) to propagate humanity (plus male seed). But "men" could still be influential in evolution even if they no longer exist in the form present in this room, as we shall see. This also takes us back to the much-debated and still-unresolved question of why there are two sexes at all. That will not be resolved in this lecture.

Slide 11

• Evolution as fact• How evolution works• Why we might stop evolving• Why we are still evolving • Mankind's evolutionary future

Are we still evolving despite modern medicine?

Darwin wrote "The Descent of Man" as an account of human evolution. My primary purpose is not to review the origins of species, including Homo sapiens, but rather to ask whether we are still changing as human beings. The goal of much of modern medicine and culture is effectively to stop evolution (Balter Science 2005). Is that happening?

Slide 12 "I found your

evidence for evolution very

convincing – but I still don't believe it"

Notwithstanding some obstacles faced by other biologists in public lectures, I'm going to assume you all believe in evolution by natural selection (quoted from M Pigliucci, Science 2009).

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Slide 13

Evolution by natural selection

Heritable variation

Selection

Ex: Antibiotic resistance

What is evolution by natural selection and how does it work? A brief reminder of the essentials will set the scene. Broadly, evolution is the change over time in a species' gene pool; i.e. all the genes in all the individuals alive at one time. DNA inevitably changes over time through random mutation, and because some individuals of a species happen to have more offspring than others. But we want to distinguish between random changes in a population (genetic "drift") and changes that are driven by natural selection – where individuals are (comparatively) favoured or disfavoured because of characteristics determined by the genes they have inherited. Significant changes in human populations take 100s (at least) and 1000s of years, but we can watch genetic changes happen in populations with generation times that are short compared to ours (e.g. hours). The evolution of antibiotic resistance is a good example: left, studs have different drugs, those with small rings kill fewer bacteria growing on the dish; right, antibiotic kills bacteria with low-intermediate levels of resistance, and only those with high levels of resistance survive to pass on their genes (one way or another). Sub-therapeutic dosing allows more of the orange types to survive with the red ones.

Slide 14 Darwin’s universals

Galton’s heredityJames’s instinctsDe Vries’ genesPavlov’s reflexesWatson’s associations Kraepelin’s historyFreud’s formative experience Boas’s cultureDurkheim’s division of labour Piaget’s development Lorenz’s imprinting

When explaining the outcome of evolution, the question is not genes (nature) or environment (nurture). Rather we should ask how the environment influences living organisms (in this lecture, humans) via their genes. As Ridley puts it: humans are a combination of Darwin’s universals, Galton’s heredity, James’s instincts, De Vries’s genes, Pavlov’s reflexes, Watson’s associations, Kraepelin’s history, Freud’s formative experience, Boas’s culture, Durkheim’s division of labour, Piaget’s development and Lorenz’s imprinting. Genes are not mere blueprints, and not just the carriers of heredity. They are active during life, switching each other on and off and responding to the environment. They are both cause and consequence of actions.

Slide 15

Twin studies: most diseases depend on genes * environment

Heritability of diseases 0 all environment 1 all genetic

Most "genetic" diseases are not due purely to gene defects, but rather to the interaction between genes and environment. "Heritability" measures how much of each. Most diseases do not score either 0 or 1, but something in between. One way to measure heritability is by comparing twins. Identical twins (monozygous, MZ twins) are twice as genetically similar as fraternal twins (dizygous, DZ) and so heritability is approximately twice the difference in correlation between MZ and DZ twins.

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Bigger differences between MZ and DZ suggest that a condition is more heritable, i.e. it has a stronger genetic component. Compare autism and alcoholism.

Slide 16

Among smokers, genes increase risk of lung cancer

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A major challenge in genetic analysis is to understand how genes interact with environmental exposures, like tobacco smoking. It could be that a gene appears to have a small effect, only until the right kind of exposure comes along. Lung cancer is largely caused by smoking. Tobacco is responsible for about 5m premature deaths every year and smoking is clearly the largest risk factor. But three recent genetic analyses suggest that, among smokers, some people may be as much as 80% more at risk than others because of their genes (Thorgeirsson Hung Nature 2008, Amos Nature Genetics 2008).

Slide 17 Evolution without Destiny

"No purpose…nothing but blind, pitiless indifference"

R Dawkins"Incipient compost: assemblages of complex

molecules that, for no greater purpose than to secure sources of energy against competing claims, have developed the ability to speculate"

G Monbiot

My last-but-one point in this evolutionary primer is that evolution has no pre-determined destiny. Some have been shocked to think that evolutionary history is a counter-argument to divine creation; more shocking, perhaps, is that evolution is taking us nowhere special. Destiny is in our hands, if we can organize it. By the end of this lecture you may or may not be convinced that we can.

Slide 18 "Still" evolving? AD = recent

Continuous adjustment

1-10s

10s-100s

100s-1000s

>1000sTime (years)ProcessType

Incentives, market design

Playing game, transactions

Rules, politics, laws, rights

Norms, culture, tradition, religion

Gene, natural selection

Resource allocation

Governance

Formal institutions

Informal institutions

Genetic evolution

Lastly, a note on time scales. When I say "still" evolving, I would like that to mean right now. The methodological problem in human evolution is that we can detect shifts in the balance of our genes only over centuries. These typically take much longer than the various processes of cultural evolution listed here.

Slide 19

"There's been no biological change in humans in 40,000 years…"

"… everything we call culture and civilisation we've built with the same body and brain"

Stephen Jay

Gould

A large set of evolutionary A-listers think, or would like to think, that human evolution has stopped. Why is that? (Forget Nobel prizes; this is Gould receiving the ultimate accolade, an appearance on the Simpson's.)

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Slide 20 "Evolution is over in humans"

• Few die before having children• Little variation in number of children• Few small, isolated populations

Steve Jones

UCL geneticist Steve Jones has given 3 reasons why evolution has stopped: (1) few die before having children, (2) there is little variation in number of children, (3) there are very few small, isolated populations. Referring to (2), the picture is of Moulay Ismail, an 18th century King of Morocco, who is said to have fathered 888 children (S Jones 2009). Mohamed bin Laden had 22 wives and 53 children, while his son Osama had 5 wives and 22 children. These men fathered a realtively large proportion of all children; it's also been suggested that older men have error prone sperm (with mutations). Factor (3) is that small isolated populations could historically change at random as genes are accidentally and randomly lost. As the world's population becomes increasingly connected, there is less opportunity for such random change, and inbreeding is becoming less common.

Slide 21

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Natural selection is not a cure for cancer

Age of conception and all cancer deaths in UK

These data from the UK amplify the point about death after reproduction. Most deaths from cancer occur after reproductive age, so a random mutation that protects individuals against cancer has no comparative reproductive advantage (though remember that human reproductive lives are not complete until they have finished investing in their children).

Slide 22 "1950s social science, in order to validate

itself, needed a homogenous humanity…"

Henry Harpending

There are reasons other than biology for wanting to believe that evolution has stopped. Here a methodological point.

Slide 23

" I would rather believe that significant human biological evolution stopped 50,000-100,000

years ago, before races diverged…

…which would ensure that racial and ethnic groups are biologically equivalent"

Stev

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Steven Pinker has amplified this as an ethical point (New Scientist 2006). Once culture emerged, it provided non-genetic means to adapt to change, such as more technology or culturally inherited changes in behaviour. Medicine is one of these cultural changes.

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10 million children under 5 die each yearmostly of cheaply preventable conditions

3.6 million from undernutrition

With that background, I'm going to look at the evidence why we might be evolving, starting with 2 of Jones's premises. First, survival to reproductive age. Among 60 million deaths each year, 10 million are children under 5 years. They die mostly in Africa and in the Indian sub-continent (red dots in the background to this slide), and they die mostly of conditions that cost very little to prevent. Four million die within a month of birth. Another 4 million or so from pneumonia and diarrhoea. And underpinning many of these immediate causes of death is malnutrition.

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Fate of 100 boys born in different countries in 2001

The survival curves of various countries give us some insight into why this is. At the high end of life expectancy, the UK is like Japan. Russia used to be more like the UK, but has suffered huge additional mortality since the collapse of the Soviet Union, especially among middle age men. India dies better than Russia in middle age, but still suffers from relatively high child mortality. The most striking feature of Zimbabwe in recent history has been the extraordinary loss of life in middle age, due to HIV/AIDS. Sierra Leone has not been so heavily affected by AIDS, but suffers appalling high child mortality.

Slide 26 Mortality rates were higher than

average in cities during the 1860s

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Cities: places to evolvedeath rates higher in cities in 1860s

These high death rates in London characteristic of European cities that persisted into the 19th century (cf cities with England & Wales on average). For the whole country the average is higher because life spans were longer in rural areas (Szreter Econ Hist Rev 1998). In Europe today, about 70% of people live in urban areas. In the Europe of 1800, only 10 to 15% of people did so, partly because of the atrocious living conditions. Cholera, dysentery, measles, plague, smallpox, tuberculosis, typhus, and other infections, exacerbated by undernourishment, imposed an “urban penalty” such that deaths, mostly of children, exceeded births. London, Paris, and other European cities could only grow by immigration from the countryside.

Slide 27

London and other urban centres have higher than average infant mortality, 2004

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The differential is still true now, to a small degree. In the rich world, the urban advantage may once again have been lost because cities like London have high concentrations of people living in poverty, with consequently poorer health (here infant mortality). In fact, the differential is likely to be higher in London (and other cities) than elsewhere because cities are more unequal socially.

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Slide 28

Fertility around the world Total fertility rate

Average number of children born to each woman

in 2005

Herbert Spencer who coined the term "survival of the fittest", but natural selection happens through differential reproductive success. The differential is still great: fertility rates remain highest in Africa, the Middle East and South Asia, where 3-8 children are born to each women. In the rich world, many countries in Europe have fertility below the replacement rate of 2.1. This is a pre-requisite for evolution, but we also have to ask to what extent the differential has a genetic rather than an environmental basis.

Slide 29 Looking for evolution

Unusually common genes?

Favoured mutations with known function?

That dispatched 2 of the premises. But can we actually detect evolutionary change? The fantastic acceleration in genetic screening methods offers 2 methods of detecting evolution: (1) Evidence that certain genes are more common than expected; a powerful approach compares the frequency of an allele in a population with the genetic diversity within a haplotype (characteristic DNA sequences) to which it belongs. If the allele is common due to random drift over a long time, the adjacent region of the genome should show considerable variation due to genetic recombination, the exchange of DNA between chromosomes. But if the variation is less than expected, the allele may have risen to high frequency in a much shorter period of time, a tell-tale sign of selection (Balter Science 2005). If selection occurs in one population but not in another, frequency differences between populations provide another sign of selection. One way to do this in practice is with SNPs (snips). A Single Nucleotide Polymorphism is a change of a nucleotide at a single base-pair location on DNA (picture David Hall, Gringer). There are more than 5m common SNPs. (2) Better still, but harder to do, we'd like to know what the mutations in a gene actually do; to find out why the altered protein it codes for has been favoured over no change.

Slide 30

2000 (7%) genes subject

to natural selection in past 80,000

yrs

SNiPs and sweeps

Cochran and colleagues examined around 2000 examples of gene "sweeps" in an African population and 2000 in European populations. Advantageous alleles are sweeping through the human population in these regions – evidence of natural selection at work.

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Slide 31

Accelerating selection for human genes in the last 40,000 years

Genomic surveys in humans identify large rates of recent positive selection. Using a 4m SNP-haplotype database Cochran and co found that selection has accelerated greatly during the last 40,000 years. The sweeps began earlier in Africa than in Europe, perhaps 80,000 and 40,000 years ago, respectively. They can be dated by looking at the degree to which the linked SNPs have started to break down through the continuing process of genetic recombination. The proposition that these and other signs of more recent human evolution are the result of rapid cultural changes, triggered by the invention of agriculture and urbanisation. This can be seen in evidence of selection on specific genes such as those that influence the physical ability to form words or to metabolise new foods. The fall to zero approaching time present is an artefact of the analysis.

Slide 32

Revolution and Evolutionrapid population growth and Neolithic agriculture

The faster rate of selection would have been promoted by population growth. These are historic and prehistoric population size estimates for human populations; key features are the larger ancestral African population size and the earlier Neolithic growth in core agricultural areas (Hawks PNAS 2007). Larger populations generate more new selected mutations. Human demographic growth is linked with past changes in human cultures and ecologies. Both processes have contributed to the extraordinarily rapid recent genetic evolution of humans.

Slide 33 Genes for human brain size

• Microcephalin 14,000- 60,000 years old, now carried by 70% of people

• ASPM 500-14,000 years old, now carried by 1/4 of global population

ASPM

Mic

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□ tonal

■ non-tonal

What do selected genes do? Why are they selected? Here are some examples, variably persuasive, and more or less recent. Lahn (Univ Chicago) found that 2 genes involved in determining the size of the human brain that emerged in recent human history and swept quickly through the population. One, a version of microcephalin, arose between 14,000 and 60,000 years ago and is now carried by 70% of people. The other, a variant of the ASPM gene, is as recent as 500 to 14,000 years old and is now carried by about 25% of people worldwide. The microcephalin gene is relatively rare in sub-Saharan Africa, and the new form of ASPM is most prevalent in people from Europe and the Middle East, suggesting that both mutations originated in non-Africans after human ancestors migrated out of Africa. The function of these genes is not yet known. However, there is an intriguing association between the frequency of these genes and the distribution of tone languages, (Chinese, Thai, Yoruba, Zulu) in which the pitch or “tone” of words and syllables makes a difference to word meaning) and non-tone function of the population frequency of the

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"derived" alleles of ASPM (horizontal axis of graph) and Microcephalin (vertical axis). In the bottom-left quadrant there are only tone languages, at top-right only non-tone languages, while at top-left there is a mixture (Dediu PNAS 2007).

Slide 34

Adventure genes: the dopamine D4 receptor

Migrant peoples of past 1,000-30,000 years have higher frequency of 7R alleles

The spread of genes with more-or-less known function: one form of the dopamine receptor gene DRD4 has become much more common over the past few thousand years. The DRD4 (dopamine receptor 4) gene is active in the regulation of dopamine, a neurotransmitter that (among other things) mediates pleasure and emotion. Different versions (alleles) of this gene have been associated with ADHD, autonomic nervous system dysfunction, autism, depression, and the personality trait of novelty seeking. The 7R allele appears to have been emerged about 40,000 years ago. Populations who migrated farther in the past 30,000 to 1,000 years ago had a higher frequency of 7R (Chen 1999). Nomadic populations also have higher frequencies of 7R alleles than sedentary ones. As Harpending (2009) comments, two of the best known ethnographies of the 20th century are titled “The Harmless People,” about the !Kung who have few or no 7R alleles, and “The Fierce People,” about the Yanomamo with a high frequency of 7R.

Slide 35

The Funnel Beaker Culture 3500BC

TRB 5000-6000 years BP north-central Europe

Raising cattle, drinking milk keeps lactase genes turned on

>99% Dutch & Swedes lactose tolerant

The TRB culture is named after the characteristic ceramic beaker with a funnel shaped rim called Trichterrandbecher in German and Trechterbeker cultuur in Dutch. Sometimes considered the first farmers of the North European Plain, TRB made several innovations e.g. the first wheeled carts. Domesticated cattle predominate in most areas, and they provided milk, which explains the origin and selection in this area of the gene allowing adults of Northern European descent to digest lactose. That gene is almost universal among people inhabiting that area on northern Europe today.

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Slide 36 Europeans and Africans converge

• 43 ethnic cattle herding groups of East Africa• Lactose tolerance evolved 2700-6800 years ago• 3 independent mutations• Evolution uses different mutations to reach the same goal

However, there are several regulatory mutations affecting lactose tolerance in northern Europe and east Africa. In 43 ethnic groups of East Africa, Tishkoff found 3 new mutations, all independent of each other and of the European mutation, which keep the lactase gene permanently switched on. The principal mutation, found among Nilo-Saharan-speaking ethnic groups of Kenya and Tanzania, arose 2700 to 6800 years ago. This fits with archaeological evidence suggesting that pastoral peoples from the north reached northern Kenya about 4500 years ago and southern Kenya and Tanzania 3300 years ago. Genetic evidence shows that the mutations conferred an enormous selective advantage on their owners, enabling them to leave almost 10 times as many descendants as people without them. The mutations have created one of the strongest genetic signatures of natural selection yet reported in humans. This in an example of convergent evolution due to strong selective pressure resulting from shared cultural traits—animal domestication and adult milk consumption (Tishkoff Nature Genetics 2007).

Slide 37 Iceland deCODEs baby boom

Women with altered chromosome 17 have 3-4% more children

Baby boost: women with an inversion in a region of chromosome 17 have more children. Direct evidence that a particular allele actually boosts reproduction is hard to find in humans. But deCODE Genetics in Reykjavik discovered a variant of human chromosome 17 associated with a previously identified haplotype called H2, which they estimate arose 3 million years ago. H2 carriers make up about 18% of Icelanders and 21% of Europeans, but only about 6% of Africans and 1% of Asians. To see whether the relatively high frequencies in Europeans represented natural selection, the team genotyped 29,137 Icelanders born between 1925 and 1965. Female H2 carriers had about 3.5% more children than H1 carriers. The European version of the H2 haplotype could sweep the entire human population if it conveyed the same reproductive advantage in other people and environments. The low frequencies of H2 outside Europe suggest that, for some reason, its advantages are limited to Europe. There are several genes in the H2 region, and it is not clear which ones cause H2 carriers to have more children. H2 carriers also show a higher rate of recombination during meiosis, but one nearby gene is implicated in pregnancy complications.

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Slide 38

"Evolution" of 2 Kinds of Women?Early vs late breeders in 200-300 years?

• University-educated: 35% less "fit" than <7 yrs education• Roman Catholics: 20% "fitter" than other religions

Natural selection for 1st child earlier in life

Another study, taking a different approach (comparing 2710 pairs of identical and non-identical twins), found that natural selection is leading women to have the first child earlier in life; this tendency is partly inherited; as a result, evolution is leading to an increasing biological pressure on women to start families earlier rather than later. Within the next few generations, 200-300 years, this evolutionary trend could manifest itself either as a division in the female population between those who have children young (genes) and those who have them late (culture), or even an increase in psychological illnesses for women who continue to fight evolution by delaying their family (Owens Evolution 2008). Is this an example of genetic and cultural evolution in conflict? NB university-educated women tend to have children late, Catholics earlier.

Slide 39

Teenage parenting: social ill or natural selection?

Conception in 15-17 year-olds: up from 40.9 (2006) to 41.9 (2007)

Labour has spent £300million on trying to reduce teenage pregnancy by handing out contraception and expanding sex education. Yet pregnancy rates among under-18s in England are now higher than they were in 1995. The point here is that we think of teenage pregnancy as a purely a social problem, but evolution is at work too.

Slide 40

Teenage fertility 1970-1998Counter-evolutionary culture?

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Teenage birth rates over a 30-year period: pale bars show the number of births to women aged below 20 per 1000 women aged 15 to 19 in 1970 (basis for the ranking). The dark bars show the rates in 1998. Teenage births have declined: but it is perceived to have grown as a problem (UNICEF 2001). Is culture counter-evolutionary?

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Slide 41

Malaria and favism:glucose-6-phosphate dehydrogenase

Fauvism is about wild beasts (Matisse, Gaugin etc), but what about favism? G6PD deficiency is also called "favism" (Italian = broad beans, fava) which cause a classic reaction when eaten by people with G6PD deficiency. In males, who have only one X chromosome, mutations in the gene for G6PD on the X chromosome cause G6PD deficiency. Females who have mutations on both X chromosomes will also be deficient. G6PD is an important enzyme in red blood cells (erythrocytes), the host cells for Plasmodium falciparum, the parasite that causes the most severe form of malaria. G6PD deficiency is associated with protection against malaria (Wellems, PLoS Medicine) , notably in Africa where one form of G6PD deficiency (G6PD A-) is widespread. Known geographical variations in the G6PD gene to estimate that the A- allele probably arose in Africa about 6300 years ago and then spread rapidly across the continent; the Med allele, found in southern Europe, the Middle East, and India, is only about 3300 years old (Tishkoff Science 2001). These estimates are consistent with archaeological evidence that malaria only became a major health problem after the invention of farming, when the clearing of forests left standing water in the Anopheles mosquito could breed. Thus a cultural change led to a genetic one.

Slide 42 Malaria in pregnancy

• Variant of FTL1 gene protect fetus in womb through a maternal immune response

• Malaria affects mother-fetus immune balance• FTL1 is under active selection in Tanzania

Placental malaria (PM) caused by Plasmodium falciparum contributes significantly to infant mortality in sub-Saharan Africa and is associated with pregnancy loss. This study examined the genotype of the fms-related tyrosine kinase 1 (FLT1) in Tanzanian mother–infant pairs. FLT1 variants confer fetal fitness in utero and are associated with the maternal immune response during PM. This indicates that FLT1 is under natural selection in a malaria endemic area and that human exposure to malaria can influence the evolutionary genetics of the maternal-fetal relationship (Muehlenbachs PNAS 2008).

Slide 43

HIV/AIDS kills people of reproductive age, so we would expect strong selection for genes that protect people.

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Slide 44

CCR5 gene protects against HIVAIDS

5-14% of Europeans

Rare in Africans and Asians

Resistant type could increase sharply in Africa in 100 years

As HIV infects T cells in the blood, it docks onto a cell surface receptor called CCR5. In the mid-1990s a mutation was found in the CCR5 gene that provides strong protection against AIDS in people who have two copies of the protective allele. 1 copy of the mutation, called delta 32, delays progression to AIDS by about 2 years. The mutation is found in up to 13% of European populations but is extremely rare in other groups, including Africans. The origins of the delta 32 mutation in humans has been dated to about 700 years ago, possibly in Scandinavia, and strong selection caused it to spread. Part B shows the modern-day observed allele frequencies. In 2008, a German HIV-infected leukaemia patient received a bone marrow transplant from a donor with 2 copies of CCR5-∆32. After 600 days, the patient was healthy and had undetectable levels of HIV in the blood and in examined brain and rectal tissues. But AIDS dates only from the late 1970s at the earliest, so what was the cause of the selective pressure? Perhaps plague or smallpox, although some recent studies have favoured smallpox.

Slide 45 AIDS and malaria in DARC-est Africa

• DARC (Duffy antigen receptor for chemokines)• Duffy-negative Africans resistant to vivax malaria:

missing receptor on red blood cells denies access to malaria parasite

• Duffy-negative African Americans have 40% increase in chance of acquiring HIV.

• Explains 11% of the HIV burden in Africa?

We've known about Duffy and P vivax since 1950, but there is a new and controversial twist to the Duffy story. US and UK scientists this year found that Duffy might increase their vulnerability of carriers to HIV infection by as much as 40% because of the way it allows the HIV virus to attach to red blood cells. The findings, If extended to all Africans, could explain an estimated 11% of the HIV burden in Africa. (Images: left, a lymphocyte immune cell full of newly manufactured HIV particles (red); centre, red blood cells invded by P falciparum malaria parasites.)

Slide 46 Sexual selection: more than ever?

Natural selection isn't the only reason why a gene might become more prevalent. Another driving force is sexual selection. High rates of migration, outbreeding, and cross-ethnic mating are recombining genes at unprecedented rates (G Miller, U New Mexico). S Jones sees globalisation as a force reducing genetic drift; Miller sees it as a process that encourages assortative mating: (1) The vast human population contains a greater diversity of genes than ever, (2) assortative mating - for intelligence, personality traits, mental health, physical health, attractiveness - is getting ever more efficient through higher education, urbanisation, singles' ads, internet dating and speed dating. Taken together, that is likely to mean that advantageous new mutations have a greater opportunity than ever to become fixed in the population. People are more likely to meet and have children with someone who is like them

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(www.tribuneindia.com).

Slide 47

How do we evolve? genetics and epigenetics

Prenatal exposure to famine in Dutch "Hunger Winter" leaves imprint on DNA after 60 years

There is genetics, but there is also a process called epigenetics: heritable changes in gene function that occur without a change in the sequence of the DNA . The Dutch famine of 1944-45 was known as the hongerwinter ("Hunger winter"). Left, a letter of commemoration given to a grocer whose shop served as a Red Cross point giving out the "Swedish bread". The transport of coal from the liberated south also ceased. Right, gas and electricity were shut off. People chopped down trees and dismantled empty houses to get fuel. The amount of food available on ration dropped steadily. 18,000 people died. Individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944–45 have, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. Early-life environmental conditions can cause epigenetic changes in humans that persist throughout life, and can be transferred to the next generation (Heijmans PNAS 2008).

Slide 48 The Runaway Human Brain

Mind shapes environment………………Environmentshapes mind

Wills claims that humans, uniquely, have a developing culture. Culture has challenged human brains and led to more complex brains as the species involved. This process continues today. The defining feature of human evolution, in Wills' view, is that our minds have shaped our environment, which in turn has led to evolutionary changes in the way we think.

Slide 49 Not all changes are genetic

32 teeth in a size 28 mouth

Although the evolution of measurable traits such as modern human skull shape may be due to random drift, some changes in human body form may have more to do with cultural and environmental factors such as diet. Over the past 10,000 years, there has been a significant trend toward rounder skulls and smaller, more gracile faces and jaws (C Larsen, Ohio State University). Most of the change is probably due to how we use our jaws rather than genetic evolution. With the rise of farming, humans began to eat much softer food that was easier to chew. The resulting relaxation of stress on the face and jaw triggered changes in skull shape. The dramatic and worldwide increase in tooth malocclusion, tooth crowding, and impacted molars are also signs of these changes: Our teeth are too big for our smaller jaws. Non-Western people who eat harder textured foods have very low rates of malocclusion. It is not genetic, but rather reflects the great plasticity of bone. It is a biological change

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but heavily influenced by culture.

Slide 50 Drought tolerant humans?

Late 21st

century

People living under water stress 3-6bn

Frequency drought x2

Duration drought x6

Drought-affected land area x10-30

What future for evolution by natural selection? First, climate change. This 2006 photo shows a resident of a drought ravaged Wajir in Kenya's north-eastern province walking among livestock carcasses following a prolonged drought that has devastated the region's herds (AFP/Getty Images). Shifting rainfall patterns, increased rates of evaporation and melting of glaciers, combined with population and economic growth, are expected to increase the number of people living in water-stressed water basins. Rough calculations suggest increases from about 1.5 billion in 1990 to 3–6 billion by 2050. By the 2090s, climate change may bring a doubling in the frequency of extreme drought events, a 6-fold increase in mean duration, and a 10–30-fold increase in the land area in extreme drought (WHO 2008). Drought-tolerant humans?

Slide 51

How many people will die in the next flu pandemic?

0

10

20

30

40

50

1918-20 1957-58 1968-70

Mill

ions

of f

lu d

eath

s Re-running the 3 pandemics of the

20th century

Spanish Flu H1N1 Asian Flu

H2N2

Hong Kong Flu

H3N2

How big will the next flu pandemic be, and when will it be? Some scientists have tried to assess this by re-running the 3 pandemics of the 20th century under contemporary demographic conditions. The conclusion – it can be no other – is that we do not know. We will not know until we understand the transmissibility and virulence of the H5N1 virus (if that is the formula). Vigilance is the key.

Slide 52 Cystic fibrosis: restoring gene function

Genetic engineering must distinguish between repairing gene function, and altering the germ plasm for all future generations. Cystic fibrosis is a hereditary disease affecting the lungs, sweat glands and digestive system. Both the lungs and pancreas produce abnormally thick mucus, and mucus in the lungs (left picture in blue) can encourage bacterial growth, leading to severe respiratory infections. Upper right: comparison between the DNA sequence between a healthy individual and a patient with CF. Dotted lines running across the image indicate the mutation site. CF sufferers have a missing CTT code which means that the CFTR protein does not function. Lower right: chromosome spread of a man with CF. At upper right, the patient's pair of chromosome 7's are highlighted with an arrow. The code 7q11-q32 indicates the region on the chromosome where the offending mutation is found. Isolation and cloning of the gene opens the way for gene therapy for each individual with CF: the addition of a working copy of the faulty gene into the appropriate cells of the body. Instead of treating the symptoms of the

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disease, like most conventional medicines, gene therapy has the potential to correct the underlying cause.

Slide 53 Changing the germ line: for what?

Changing the hereditary cells, the germ line, is also becoming possible. This is a fluorescent transgenic mouse, which glows green under blue light due to green fluorescent protein from a glowing jellyfish. The egg from which this mouse developed was infected with a virus carrying the jellyfish gene, causing the gene to be incorporated into the mouse's DNA. A gene is a segment of DNA (deoxyribonucleic acid) which has a specific function, in this case the production of GFP in the mouse's cells. This genetic engineering technique could be used to mark cancer cells in human patients and follow their movement around the body (Picture: Eye of science /Science photo library). It could also be used, in principle, to manipulate the human genome, though we are nowhere close to achieving that scientifically or ethically.

Slide 54

Human genetic engineering: what could it fix?

6000 diseases caused by single mutationsbut purely hereditary, severe diseases rare

One birth in…………………………….……..Cystic fibrosis 2 300Duchenne's muscular dystrophy 3 000Huntington's disease 20 000

One thing to remember is that only a few genes have major effects on attributes that affect health. There are about 6000 disease caused by single gene defects (mutations), but severe and fatal disorders that are purely hereditary are rare, for the obvious reason that people who die young do not pass on their defective genes. One example is Huntington's disease, genetically programmed degeneration of brain cells, and the picture show thinning of the brain cortex in early disease and during disease progression (from red least thinning to yellow greatest thinning). But most determinants of health are governed by numerous genes and, as I said at the start, their complex interaction with the environment. So don't expect many health remedies from genetic engineering soon, either to repair gene function or by changing the germ line.

Slide 55 Cyborgs: free from evolution at last?

In the long run, will we end up using new technology to promote genetic evolution (last slide), or to stop it altogether (this one)? Ray Kurzweil imagines humans merging with technology to become cyborgs so that biological evolution finally becomes obsolete (New Scientist 2006). The picture on the left is fantasy artwork; the real thing is on the right, a newly-built molecular wheel and axle (Lee Nature 2009).

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Slide 56 Evolving… but where to?

Dennett "hardy remnant of our species which can survive on

earthworms while living in underground burrows…"

Miller "In 1000 years… more beautiful, intelligent, symmetrical, healthy… due to 40 generations of genetic screening against harmful mutations"

In conclusion, humans will continue to evolve in the sense that the balance of genes in the H sapiens gene pool will change. The evidence points to continuing natural selection, backed by other mechanisms like sexual selection and random genetic drift. This is an era of rapid technological progress and a fast changing environment, and these are conditions under which natural selection can continue to act. Technological change has driven natural selection in the past, so why not now? It's easy to imagine selection pressures that could be acting today e.g. thinking again about 18th century Moroccan kings: could willingness to be a sperm or egg donor be favoured by current selection? Could caesarean sections select for genes that allow babies to grow bigger in the womb? These are open questions. When experts like Geoffrey Miller and Darwin look-alike Daniel Dennett hold strongly differing views, you can be sure that we have no idea where we are taking evolution, or where evolution is taking us.