1. technology and computing
2. operating systems
3. windows

SBL100 for 2nd Semester 2014-15
Slot C - Tuesday/Wednesday/Friday - 8am to 8.50 am
About the Course
Course Content
James Gomes
Evolution and molecular perspectives
Classification of systems in biology
Cellular assemblies
Geometry, structures and energetics
„ Attendance: >75% (5 marks) (Based on total number of lectures taken) „ Pass marks: 35%
„ Exam: Objective type questions (written)
Manidipa Banerjee
Infection and disease
Evolution in disease‐synergy and antagonism „ Marks distribution: † Minor I: 20
Immunology
†
Chinmoy Sankar Dey
Fundamental units of life
From prokaryotes to eukaryotes Single to multicellular organisms
Cancer biology Stem cells Biological machines
†
†
Minor II: 20
Major: 30
Practice/practical: 25 marks
„ Office hours for the students to meet faculty: †
JGomes, SBS IITD
Tuesday/Wednesday/Friday
5 to 6 pm.
1
EVOLUTION
LECTURES 1‐4
Acknowledgements:
Alberts - Molecular Biology of the Cell
Scitable by Nature Education
Nature Resources
Internet resources
The history of life
„ The Big Bang occurred 15 billion years ago
† It was so hot that all the matter would have been in the form of
protons and neutrons
† Neutrons decay into more protons; hydrogen and helium created
† The universe expanded to form the heavier elements „ Then supernovas, galaxies, stars and solar systems
„ Our solar system was formed 4.5 billion years ago
„ The Earth was formed largely out of the heavier elements, including carbon and oxygen
† Somehow some of these atoms came to be arranged in the form of molecules of DNA about 3 – 3.5 billion years ago
„ It took 2.5 billion years for life to evolve from the earliest cells to multi cell animals
† Another 1 billion years to evolve through fish and reptiles to mammals
† Then evolution seemed to have speeded up and only took about a hundred million years to develop from the early mammals to us JGomes, SBS IITD
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Was life supposed to evolve?
„ What we normally think of as life is based on chains of carbon atoms with a few other primary atoms such as oxygen, hydrogen, nitrogen and phosphorous. „ What about silicon‐based life?
„ Yes, maybe! but carbon‐based seems the most favorable because it has the richest chemistry
The Anthropic Principle:
Principle
For a given universe, it is possible, that for a small number the values physical constants, will allow the existence of objects like carbon atoms that can act as the building blocks of living systems JGomes, SBS IITD
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Why did life occur?
„ We don’t have an answer!
„ The anthropic principle tells us that it would have happened if not on planet earth, then on some other planet
„ We do know, by observation, what are the properties that define life
† Have a set of instructions that tell the system how to sustain and reproduce itself
† A mechanism to carry out the instructions
„ By the second law of thermodynamics, to do this, we need to have order
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Order
„ How do you determine if a system has order ‐ in the sense of structured‐ness and organization ?
† Self Organization
† Complexity
† Emergence of new properties „ One of the most fundamental problems in biology concerns the origin of forms and their associated functions
„ It has been an important question of developmental biology
Second law of Thermodynamics state that the entropy (disorder) of
the universe is continuously increasing with time.
Therefore, decrease of entropy, as in a cell, is permitted if the
corresponding increase in entropy in the environment is greater.
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Order in inanimate systems
a) In a liquid layer, molecules are agitated by thermal motion. b) The molecules in the liquid layer are heated from below (red zone) and self‐organize into rolls (drawn in cross‐section) when the temperature reaches a critical value (tc). At this value, the molecules start to move collectively either up or down at point 0, which determines the alternative orientation of the rotation of the rolls throughout the layer. The orientation of the rotation choice is unpredictable and determined by local fluctuations at tc
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Self Organization in Chemical Reactions
Photographs taken at 30 s
intervals
Belousov–Zhabotinsky reaction J. Theor.
Biol. (1973) 40, 45-61
In the system, propagation of a single wave was observed under following conditions: NaBrO3 = 0.23 M, bromomalonic acid = 0.16 M, (Ferroin) Fe(phen)3 = 0.003 M, H2S04 = 0.26 M, T = 14°C. The wave velocity equalled approximately 0.01 cm/s.
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The boundary: inanimate to animate
„ The concepts of interaction free energies, molecular geometry and entropy, when taken together, furnish a framework for a theory of self‐assembly or self‐organization
„ Micelles and bilayer vesicles assembly are driven by hydrophobic and hydrophilic interaction ‐ of two ʹopposing forcesʺ „ Size of the micelle is determined by ʺoptimal surface areaʺ per head group at which the total interaction free energy per lipid molecule is a minimum.
Biochimica et Biophysica Acta,
201
Acta, 470 (1977) 185-185--201
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Some basic rules for micelle shapes
Adv Mater 2003 15 (16)
„ Surfactant first forms a bilayer and then closes to form a vesicle
„ The ratio of the hydrophobic to hydrophilic portion of the molecule determines the radius of curvature at the interface
v
Kl 2
= 1 + Hl +
al
3
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Vesicle Size and Shape
Adv Mater 2003 15 (16)
„ Depends on mixing entropies (pull towards many assemblies) and molar bending energies ( tends towards a smaller number of vesicles)
„ ΔA is the difference in area, v is the dimensionless volume to area ratio
JGomes, SBS IITD
AFM image of a polymer
vesicle. The erythrocytelike shape arises from the
evaporation of water from
the vesicle interior,
leaving the prominent rim
11
Similarity in structure of self-organized
biological and non-biological entities
(a) High-genus block copolymer
vesicle (b) structure of a diatom
[Adv Mater 2003 15 (16)]
„ Genus order g > 100
TEM image showing
ordered chains of
prismatic BaCrO4
nanoparticles prepared in
AOT microemulsions
Angew. Chem. Int. Ed.
2003, 42, 2350 – 2365
JGomes, SBS IITD
DMPC–apoE CT domain
complexes; reconstituted
lipoprotein particles were
stained with 2%
phosphotungstate for
visualization [Biochem. J.
(2005) 387 (747–754) ]
12
Nature Documentaries
„ Evolution
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Urey Miller Experiment
„ In 1953 Stanley Miller and Harold Urey performed the first experiment that produced amino acids in what was assumed to be a pre‐life atmosphere. They passed a mixture of water vapor, methane, hydrogen and ammonia gases through an electric arc to simulate what would happen if these gases were subjected to lightning.
Result: „ 10 biologic amino acid types
25 non‐biologic amino acid types Formaldehyde
Sugars
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First proteins
„ In the presence of kaolinite, amino acids are picked up from an aqueous solvent and brought into solid solution
† Amino groups become hydrogen bonded to structural oxygen
† In water, amino acids cannot polymerize because of dipole‐dipole interactions
† In solid solution, however, amino acids will polymerize, because the solvent medium does not interfere
† about 1000 times more amino acids were polymerized to peptides „ Kaolinite is also instrumental in preferentially synthesizing pentoses
and hexoses from formaldehyde and transforming them into polysaccharides
„ Preferential polymerization of L‐amino acids on kaolinite can be attributed to the inherent enantiomorphism of the edges of the octahedral layer of kaolinite
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Formation of polynucleotides and
polypeptides
„ Nucleotides of four kinds (here represented by the single letters A, U, G, and C) can undergo spontaneous polymerization with the loss of water. The product is a mixture of polynucleotides that are random in length and sequence. „ Similarly, amino acids of different types, symbolized here by three‐
letter abbreviated names, can polymerize with one another to form polypeptides. Present‐day proteins are built from a standard set of 20 types of amino acids.
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Polynucleotides as templates
„ Preferential binding occurs between pairs of nucleotides (G with C and U with A) by relatively weak chemical bonds
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Replication of a polynucleotide sequence
„ The original RNA molecule acts as a template to form an RNA molecule of complementary sequence.
„ This complementary RNA molecule itself acts as a template, forming RNA molecules of the original sequence. Since each templating molecule can produce many copies of the complementary strand, these reactions can result in the ʺmultiplicationʺ of the original sequence
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Conformation of an RNA molecule
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Evolutionary significance of cell-like
compartments
„ Any improved form of RNA that is able to promote formation of a more useful protein must share this protein with its neighboring competitors. „ If the RNA is enclosed within a compartment, such as a lipid membrane, then any protein the RNA causes to be made is retained for its own use; the RNA can therefore be selected on the basis of its guiding production of a better protein.
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Central Dogma
Suggested stages of evolution from simple self‐replicating systems of RNA molecules to present‐
day cells. Today, DNA is the repository of genetic information and RNA acts largely as a go‐between to direct protein synthesis
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Last Universal Common
Ancestor
„ The evolution of the translation apparatus occurred in a series of increasingly complex stages, rather than all at once, „ The stages subsequent to the establishment of the basic mechanism were concerned by and large with increasing the mechanismʹs accuracy, and possibly speed as well
J. Mol Evol 10, 1‐6, 1977
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Evolution of Metabolic Pathways
„ The cell on the left is provided with a supply of related substances (A, B, C, and D) produced by prebiotic
synthesis. One of these, substance D, is metabolically useful. As the cell exhausts the available supply of D, a selective advantage is obtained by the evolution of a new enzyme that is able to produce D from the closely related substance C. Fundamentally important metabolic pathways may have evolved by a series of similar steps. „ On the right, a metabolically useful compound A is available in abundance. An enzyme appears in the course of evolution that, by chance, has the ability to convert substance A to substance B. Other changes then occur within the cell that enable it to make use of the new substance. The appearance of further enzymes can build up a long chain of reactions. JGomes, SBS IITD
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Predation to new cellular structures
„ A close relative of present‐day cyanobacteria that lives in a permanent symbiotic relationship inside another cell. The two organisms are known jointly as Cyanophora paradoxa. The ʺcyano‐
bacteriumʺ is in the process of dividing
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Animal and Plant Cell structures
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Cellular Membrane System
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Summary
„ Autocatalytic mechanisms fundamental to living systems began with the evolution of families of RNA molecules that could catalyze their own replication. „ Families of cooperating RNA catalysts developed the ability to direct synthesis of polypeptides. „ Accumulation of additional protein catalysts allowed more efficient and complex cells to evolve, the DNA double helix replaced RNA as a more stable molecule for storing the increased amounts of genetic information required by such cells
„ Present‐day living cells are classified as procaryotic
(bacteria and their close relatives) or eucaryotic.
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Development and Evolutionary Change
Lecture 2
Development and Evolutionary
Change
„ All anemonefish (clownfish) begin life as males. The largest male in the social group will change sex to become the group’s only female
„ The social environment determines its sex
„ If the female is removed, the largest male changes into a female
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Evolutionary Developmental Biology
„ Evolutionary developmental biologists investigate how the course of evolution has been influenced by heritable changes in the development of organisms
†
To study how genes have changed during the course of evolution. † To understand large evolutionary changes, such as the evolution of eyes, wings, and flowers, biologists study both developing and adult organisms, because the agents of evolution work not only on adults but on the “recipes” for making adults.
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Early Development Similarities
„ Adult barnacles do not clearly resemble adults of other crustaceans
„ The similarities between their larvae shows that these animals share a recent common ancestor
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„ The instructions for forming embryos are provided by homologous genes in vertebrates and invertebrates, even though the structures formed from those instructions are very different. „ The enormous variation of morphological forms found in the animal kingdom is underlain by a common set of instructions
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Regulatory Genes and Modularity
Two major ways
„ Mutations in genes that regulate developmental processes
„ Changes in the time or location of expression of developmental regulatory genes
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Mutation in a Module
Common
ancestor
„ In the insect lineage (blue) of the arthropods, a mutation in the Ubx gene resulted in a protein that inhibits a gene that is required for legs to form. Because insects express Ubx in their abdominal segments, no legs grow from these segments. Other arthropods, such as centipedes, do grow legs from their abdominal segments.
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Heterochrony – difference timing of
gene induction in different species
„ The webbing of developing salamanders disappears in most species
„ If the genes responsible for dissolving the webbing slows down, then the digits do not expand as the rest of the body
„ Results in two different adaptations
†
†
Terrestrial Arboreal
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Plant development
„ Plant cells do not move relative to one another
„ Plant cells do not move during development whereas cells move significantly during animal development and determine the final shape of the adult
„ Future reproductive cells are not set aside early during plant development
„ Instead, throughout their lives, plants continue to produce clusters of undifferentiated, actively dividing cells, called meristems. Meristems allow a plant to develop and form new organs, such as stems, roots, leaves, and flowers, as long as it grows
„ Plants have tremendous developmental plasticity
„ If an herbivore eats part of a plant, leaf meristems may grow out and replace the lost part.
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Mechanisms of Evolution ‐I
Lecture 3
Count George-Louis Leclerc de
Buffon (1707-1788)
„ Natural History of Animals, which contained a clear statement of the possibility of evolution
„ He also noticed that the legs of certain mammals, such as pigs, have toes that never touch the ground and appear to be of no use
„ He found it difficult to explain the presence of these seemingly useless small toes and suggested that the limb bones of mammals might all have been inherited from a common ancestor
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Lamarckian Evolution
„ Jean‐Baptiste de Lamarck (1744–1829)
†
First Law: A lineage of organisms could change gradually over many generations as offspring inherited structures that had become larger and more highly developed as a result of continued use or, conversely, had become smaller and less developed as a result of lack of use.
† Second Law: All the acquisitions or losses wrought by nature on individuals, through the influence of the environment are preserved by reproduction to the new individuals which arise, provided that the acquired modifications are common to both sexes JGomes, SBS IITD
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Darwinism
„ Charles Darwin (1809 ‐ 1882)
†
†
1.
2.
3.
†
1.
Darwin’s theory rests on three observations and one conclusion he drew from them.
Observations:
The reproductive rates of all organisms, even slowly reproducing ones, are sufficiently high that populations would quickly become enormous if death rates were not equally high.
Within each type of organism, there are differences among individuals.
Offspring are similar to their parents because they inherit their parents’ features.
Conclusion:
The differences among individuals influence how well those individuals survive and reproduce. Any traits that increase the probability that their bearers will survive and reproduce are passed on to their offspring and to their offspring’s offspring.
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Darwins Journey
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Darwin’s Finches
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Mendelian Inheritance
„ The inheritance of each trait is determined by ʺunitsʺ or ʺfactorsʺ that are passed on to descendents unchanged „ An individual inherits one such unit from each parent for each trait
„ A trait may not show up in an individual but can still be passed on to the next generation.
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Hardy-Weinberg Equilibrium
„ The Hardy‐Weinberg Theorem deals with Mendelian genetics
„allele frequencies in a population will not 1. change from generation to generation.
„if the allele frequencies in a population with two alleles at a locus are p and q, then the expected genotype frequencies are p2, 2pq, and q2. This frequency distribution will not change from generation to generation once a population is in Hardy‐Weinberg equilibrium.
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„ Assumptions:
Hardy-Weinberg
†
Natural selection is not acting on the locus in question (i.e., there are no consistent differences in probabilities of survival or reproduction among genotypes).
† Neither mutation (the origin of new alleles) nor migration (the movement of individuals and their genes into or out of the population) is introducing new alleles into the population.
† Population size is infinite, which means that genetic drift is not causing random changes in allele frequencies due to sampling error from one generation to the next. Of course, all natural populations are finite and thus subject to drift, but we expect the effects of drift to be more pronounced in small than in large populations.
† Individuals in the population mate randomly with respect to the locus in question. Although non‐random mating does not change allele frequencies from one generation to the next if the other assumptions hold.
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Evolutionary Implications of the
Hardy-Weinberg Theorem
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What is Evolution
„ Evolution is change in the inherited traits of a population through successive generations. When living organisms reproduce, they pass on to their progeny a collection of traits.
† patterns in a butterflyʹs wing or the number of scales on a crocodile or the spots in a leopard
† Changes (mutations) in the sequence of nucleotide bases that make up an organismʹs DNA
„ Evolution does not progress toward an ultimate or proximate goal (Gould 1989). Evolution is not ʺgoing somewhere“
„ It just describes changes in inherited traits over time. Occasionally, and perhaps inevitably, this change results in increases in biological complexity, but to interpret this as ʺprogressʺ is to misunderstand the mechanism
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Mechanisms of Evolution ‐II
Lecture 4
Molecular Ecology
„ Evolutionary relationship between species sharing the certain molecules
†
Turacin (6% copper complexed to uroporphyrin III), a naturally occurring red pigment is found only in birds of the Musophagidae
family
† Other birds, for example, get bright red colorations from carotenoids
„ First discovered by Arthur Church in 1839.
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Principle of polymerase chain reaction
(PRC) to amplify target DNA sequence
„ It is possible to take a small sample of tissue to obtain enough DNA for study. „ This contrasts with earlier approaches that often required large amounts of DNA or protein, which often meant killing the organism of study
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Molecular Eecology: Chetahs
„ The development of molecular markers has led to an explosion of studies that have used them to answer questions ranging from 1. relatedness among species
2. evolutionary history of populations
3. amount of genetic variation within a species
4. patterns of behavior
5. how patterns of gene expression can vary among closely related populations
JGomes, SBS IITD
Acinonyx jubatus, the cheetah,
has been shown to have low
genetic diversity
O'Brien and his colleagues (1983)
found that the genetic diversity
among cheetahs in South Africa
has extremely low
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Species Divergence
„ Radio telemetry to track the migration of animals. However, their mating behaviour
cannot be tracked using this method
† Reproductive success is an indication of fitness and, therefore, of the long‐term survival of a population — a fundamental issue in ecology
† A DNA‐based approach can provide much more insight into the mating behaviors of dispersing animals.
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Limitations of Molecular Ecology
„ Marker development can be time‐consuming and expensive. „ While it can be beneficial that molecular ecology is not dependent on direct observation of behaviours, this benefit can often be a limitation
„ Behaviour is not directly observed, there can often be multiple explanations for the same observed pattern
„ It is not practical to look at the entire genome of all organisms, so one must look at a small subset of markers
„ Hence the choice of marker may affect the pattern observed
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Mutation for Evolution
„ Definition: A changeinthe DNA sequence of the organism
„ What causes mutation
„ Radiation, Chemicals in the environment
„ Errors during DNA replication
„ The human genome, for example, contains over 3.1 billion bases of DNA, and each base must be faithfully replicated for cell division to occur
„ About one in every 1010 (10,000,000,000) base pair is changed
† Common Failure
„ Substitution, Deletion, Insertion, Point duplication, JGomes, SBS IITD
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Example: Mutation in Tropical Fishes
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Diverse Life Histories
„ Environmental variation
„ Life histories evolve in response to the environment (i.e., extrinsic factors) as well as to internal constraints. The environment is continually changing, giving natural selection a ʺmoving target“
„ Random Variation
„ Increased mortality and variability in mortality in the juvenile
period both favour the evolution of delayed reproduction, provided that delaying reproduction increases the chance of producing viable offspring
„ These variations may force short term reduction of fitness to achieve the long term goal of survival
…
…
Vegetative dormancy in plants
Orchids produce fruits with thousands of dust seeds
„ Predictable Environmental Variation
„ Cycles are routine and repeated, and do not change dramatically in any random or deterministic way
…
one genotype produces different phenotypes under different environmental conditions
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Environmental Influences
„ How should organisms respond to signals from the environment in order to develop adaptively?
† No single way of responding to signals from the environment results in adaptation because what environmental signals tell an organism varies with the type of signal
„Environmental signals that are accurate predictors of future conditions
„Environmental signals that are poorly correlated with future conditions. JGomes, SBS IITD
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„ Human Evolution
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Evolution of Hominins
„ Features common to all primates include limber joints, grasping hands and feet with opposable digits, face altered for stereoscopic vision and good touch sensitivity. „ These characters probably originally evolved as adaptations to arboreal life about 65 million years ago.
„ Two major groups of primates:
†
Prosimians are the most basal primates, and are small, arboreal species that move among trees by brachiating. These include lemurs, lorises and tarsiers.
† Hominoids (= apes) are within the Anthropoids, and generally have higher brain to body weight ratios and rely more on sight than on smell.
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Features of Hominins
„ Hominins probably evolved from an ancestor common with apes and chimps about 5‐7 mya. „ The lineage includes Australopithecus, which shows features intermediate between man and other anthropoids „ The lineage shows evolutionary trends in five major features: 1. Bipedal posture: upright posture and two‐legged walking. 2. A more juvenile facial shape, such as shorter jaws, flatter faces and more pronounced chins 3. Increased brain size relative to body mass, with language, symbolic thought and ability for complex tools (occurred AFTER bipedal posture)
4. Reduced size difference between sexes, probably correlated with a more monogamous lifestyle.
5. Family structure: increased pair‐bonding between mates as well as the period and larger extent of juvenile dependence on parental care.
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Footprints
„ In 1976, members of a team led by Mary Leakey discovered the fossilized footprints of human ancestors in Laetoli, Africa. The footprints were formed 3.5 million years ago when at least two individuals walked over wet volcanic ash. The wet ash hardened like cement and was then covered by more ash
„ The footprints also look remarkably like a humanʹs. In fact, they looked so human‐like, some scientists had a hard time believing that they were made by Australopithecus afarensis
(Lucyʹs species), the only human ancestor known to have lived at the time
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HUMAN EVOLUTION
„ 3D Collection
†
Explore our 3D collection of fossils, artifacts, primates, and other animals.
„ Human Fossils
†
From skeletons to teeth, early human fossils have been found of more than 6,000 individuals. „ Genetics
†
Our genes offer evidence of how closely we are related to one another – and of our species’
connection with all other organisms.
„ Dating
†
The layers that contain fossils and archeological clues can be dated by more than a dozen techniques that use the basic principles of physics, chemistry, and Earth sciences. Some techniques can even estimate the age of the ancient teeth and bones directly. JGomes, SBS IITD
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Neanderthals: larger eyes and
smaller brains?
„ Neanderthals had larger eye sockets – and a larger brain area devoted to sight – than in modern humans. When the larger visual system is subtracted from total brain size, our extinct cousins actually had a smaller rest of the brain than did fossil Homo sapiens.
Homo sapiens (Cro‐Magnon, left) and Homo neanderthalensis (Amud, right): Despite having the same total brain volume, the large eyes of Neanderthals suggest that less of the brain focused on other mental tasks. Pearce, E., Stringer, C., Dunbar, R.I.M., 2013. New insights into differences in brain organization
between Neanderthals and anatomically modern humans. Proceedings of the Royal Society B 280,
20130168, doi:10.1098/rspb.2013.0168 JGomes, SBS IITD
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Single Highly Variable Lineage
„ Analysis of the new skull suggests that these early forms of the genus Homo evolved as a single, highly variable lineage, assigned to the species Homo erectus
„ This controversial conclusion arises from how species originate: populations can diverge and become independent species or may reunite with distinctive variations of a single species. Five skulls already discovered at Dmanisi
are the oldest known fossils of the genus Homo outside of Africa
Newly reported Dmanisi cranium (center) is compared with scanned replicas of East African Homo erectus
(2 crania at top), Homo rudolfensis
(bottom left), and Homo habilis
(bottom right). 5 centimeter
scale. Credit: Georgian National Museum and Fred Spoor
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„ ancient artists decorated a stretch of limestone wall with dozens of depictions of human hands. They seem to have made the images by pressing a hand to the wall and then blowing red pigment on it, creating a sort of stencil
Hand stencils in El Castillo cave 40,800 years old JGomes, SBS IITD
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„ New Horizons in Evolutionary Theories
„ OTHER VIDEOS
† http://naturedocumentaries.org/3972/hidden‐
life‐cell‐bbc/
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