EVE100_F24_623-660 PDF Human Evolution

12/5/24 While we are the only surviving hominin, our group has a complex and species-rich history… 623 623 FIGURE 20.6 Fossils of many hominin species have been discovered, a...

12/5/24 While we are the only surviving hominin, our group has a complex and species-rich history… 623 623 FIGURE 20.6 Fossils of many hominin species have been discovered, and often more than one species was living at the same time 624 1  12/5/24 Early Out-of-Africa events, FK 20.9 625 625 Origin (200-300 K yrs. ago) and spread of modern humans, FK 20.12 Earlier Out-of-Africa events of modern humans left no descendants 626 626 2  12/5/24 Figure 21.20 The number of deleterious mutations in the human genome increases with the distance of a population from southern Africa 627 H. sapiens neanderthalensis went extinct about 30,000 years ago 628 628 3  12/5/24 Recent artists’ renderings of Neanderthal appearance 629 629 Sequencing ancient hominins 630 4  12/5/24 631 631 1. Common ancestor with H. sapiens was about 800,000 years ago 2. There are several proteins at which chimp and Neanderthal are identical and human is different. 3. Non-African chromosomes have more Neanderthal ancestry than African chromosomes. 4. About 2-4% of European genome may derive from Neanderthal introgression 632 632 5  12/5/24 Indications of inbreeding in the Altai Neanderthal individual. K Prüfer et al. Nature 000, 1-7 (2013) doi:10.1038/nature12886 633 Sequencing of a 40,000 yr old Romanian suggested he had a much more Neanderthal DNA than more modern humans and had a Neanderthal ancestor only about 200 yrs before his birth. 634 6  12/5/24 A 45,000 yr old modern human from Siberia. Q Fu et al. Nature 514, 445-449 (2014) doi:10.1038/nature13810 635 Regions of Neanderthal ancestry on chromosome 12 in the Ust’-Ishim individual and fifteen present-day non-Africans. This can be explained by interbreeding events about 50-60,000 yrs ago. Q Fu et al. Nature 514, 445-449 (2014) doi:10.1038/nature13810 636 7  12/5/24 Who were the Denisovans? Genetic history of an archaic hominin group from Denisova Cave in Siberia D Reich et al. Nature 468, 1053-1060 (2010) doi:10.1038/nature09710 A neighbour-joining tree based on pairwise autosomal DNA sequence divergences for five ancient and five present-day hominins. 637 The genome of the offspring of a Neanderthal mother and a Denisovan father Nature 561, 113–116 (2018) | Download Citation Abstract Neanderthals and Denisovans are extinct groups of hominins that separated from each other more than 390,000 years ago1,2. Here we present the genome of ‘Denisova 11’, a bone fragment from Denisova Cave (Russia)3 and show that it comes from an individual who had a Neanderthal mother and a Denisovan father. The father, whose genome bears traces of Neanderthal ancestry, came from a population related to a later Denisovan found in the cave4,5,6. The mother came from a population more closely related to Neanderthals who lived later in Europe2,7 than to an earlier Neanderthal found in Denisova Cave8, suggesting that migrations of Neanderthals between eastern and western Eurasia occurred sometime after 120,000 years ago. The finding of a first-generation Neanderthal– Denisovan offspring among the small number of archaic specimens sequenced to date suggests that mixing between Late Pleistocene hominin groups was common when they met. 638 638 8  12/5/24 639 639 FIGURE 20.14 Modern humans, Neanderthals, and Denisovans hybridized at many times and many places (Part 1) 640 9  12/5/24 General analysis of the contribution of Neanderthal and Denisovan alleles to recent adaptation in modern humans 641 Some alleles contributing to recent human adaptation have their origin in introgression events from ancient hominins (e.g., EPAS1 and high altitude adaptation in Tibetans). Other examples are pigmentation alleles and alleles possibly associated with diet (Inuits), or the immune system. 642 642 10  12/5/24 The question of gene flow from modern humans into archaic hominins remains unresolved. 643 643 FIGURE 20.16 Agriculture was invented independently at several places around the world Human culture and biology interact Multiple diseases have become common in our recent past 644 11  12/5/24 Evolutionary history of human malarial infections Gorilla, green Human, black Chimps, other 645 It had been thought that malaria was an ancient human pathogen. However, these results suggest it moved from gorillas to humans within roughly the last 10,000 yrs. The fact that genetic diversity within human P. falciparum is much lower than infections in other great apes suggests that this transfer to humans was associated with a severe bottleneck. 646 12  12/5/24 Are there human health effects due to mismatch between our ancestral biology and our recent environment (agriculture, industrial revolution)? Recent problems with wisdom teeth? 1) Skulls of pre-industrial farmers exhibit lots of dental problems. 2) So do skulls of the last few hundred years 3) But skulls of ancient hunter-gatherers have few dental problems 4) Why are wisdom tooth problems so common in modern populations? 647 647 Possible effects of agriculture (mostly domesticated grasses) and the rise of cities High population densities led to infectious disease such as measles, mumps, influenza, smallpox, cholera, typhus. Some infectious diseases jumped from domesticated animals to humans. 648 648 13  12/5/24 Do modern lifestyles increase breast cancer risk? Cancers are produced by mutations, mutations occur when cells divide, and cells divide in breasts every menstrual cycle. Hunter-gatherer females were pregnant or lactating for much more of their lives than are women in postindustrial societies. As a result, they had about 150 menstrual cycles per lifetime, whereas postindustrial women have 350 to 400. That implies about 3 times the risk of reproductive cancers in cells that divide during menstrual cycles. Obesity also increases the breast cancer risk because fat cells release estrogen. 649 649 Are allergies and asthma (and perhaps autoimmune disorders) a reflection of mismatch? The hygiene hypothesis is that our cleaner environment leads to lower rates of childhood infection and for some individuals, adult immune systems that overreact to stimuli (e.g., asthma). The “old friends” hypothesis is similar, but states that in the absence of ancestral pathogens, our immune systems don’t even develop properly. These defects also lead to overreaction to some stimuli. 650 650 14  12/5/24 Cancer as an evolutionary phenomenon About 1% of the genes in the genome – roughly 350 – are involved in oncogenesis. It is usually mutations in stem cells, not in differentiated tissue, that produce cancer. Each cell lineage in the body develops a unique history. Because there are so many cell divisions in the history of each individual, even with low somatic mutation rates, every gene in the genome mutates many times in the soma of every individual. 651 Somatic evolution is orthogonal to germline evolution 652 15  12/5/24 Cancer is produced by competition among clonal lineages generated by somatic mutations Cancer cells often display extreme genetic heterogeneity (sequencing of cancers) Cancer cells compete for nutrients and to evade the immune system. Genetic variants better at those functions increase in numbers and frequency (natural selection). Somatic evolution can sometimes produce rough adaptations to local environments, (e.g., liver vs. lung). 653 Clonal evolution in general and in cancer Note the interference of clone A with AC p16 and p 53 are tumor suppressor genes; – indicates loss of function mutation. High-grade dysplasia = severe precancerous tissue change 654 16  12/5/24 This view has become standard… 655 Phylogenetics of pancreatic cancer: Older than expected We usually think of Clonal Selection pancreatic cancer as killing quickly, but in these cases it started many years before the Diagnosis: patients died. too late Local adaptation 656 17  12/5/24 Renal cell carcinoma: Evolutionary divergence poses problems for therapy Branch lengths proportional to number of amino acid changes. Potential driver mutations indicated by arrows. Gerlinger et al. 2012 657 Renal cell carcinoma: Evolutionary divergence poses problems for therapy A primary tumor on the kidney sent metastases into the lung and chest wall. Both the primary tumor and the metastases consisted of sets of clones. Therapies designed to treat the primary tumor would miss variation in the metastases. Therapies designed to treat one metastasis would miss variation in the others. 658 18  12/5/24 Molecular characterization of glioblastoma Following chemotherapy, the surviving population was not a single resistant clone, but multiple clones with different mutations for resistance. Unless treatments eliminated all clones, survivors would persist and possibly flourish. A single biopsy of one branch will not be sufficient to indicate the problems posed by a tree. 659 Some early conclusions from phylogenetic analysis of cancer… - Phylogenetics can describe the history of the evolution of a metastatic cancer in a single patient. - Evidence for cancer as a process of clonal evolution. - Cancers often originate earlier, and are older, than we suspected. - Single biopsies of primary tumors underestimate the clonal heterogeneity of the metastases. - Clonal variation makes treatment challenging… 660 19