Evolutionary medicine has the potential to unify the teaching and learning of mechanism-based medicine.

However, many of these diseases recur in populations through repeated germline mutations because of the heterozygote advantage of the carrier state.

evolutionary medicine explains that this occurs because of long postreproductive life in humans where natural selection has been too weak to select for highly efficient mechanisms

These include obesity, type 2 diabetes, atherosclerosis, hypertension and addictive behaviours.

However, the benefit diminishes when infectious disease is well-controlled; then the high cost of the defence system becomes apparent

Infectious diseases are a primary cause of category 1 diseases and offer one of the most striking examples of the impact of genomics on medicine

Through mutations, these genes may produce proteins that cause a spectrum of inflammatory diseases such as ulcerative colitis and Crohn disease

medicinal drug metabolism is based mostly on these systems, differences acquired during the global spread of humans partly explain the variation in therapeutic response to drugs and provides the scientific basis for precision medicine

sweat glands

vulnerability during which the environment affects genome expression

We performed the test for continuity using the method described in Schraiber (49)

continuity is defined as a genetic affinity between two temporal populations without external gene flow.

tested for strict continuity

The ancient individuals were sequenced with the HiSeq X (PE150), one lane each, at Macrogen Labs. For this round of sequencing, SMP5 and K1 were not enriched.

Thirty-nine Huilliche-Pehuenche individuals were genotyped via the Axiom LAT1 Chip

The average coverage for the 24 individuals, after bioinformatics processing, was 4.36

Twenty-four Aymara individuals underwent shotgun sequencing, multiplexing six individuals on eight lanes, on the Illumina HiSeq 4000, PE125,

Blunt-end repair was performed with the NEBNext Quick DNA Library Prep Master Mix Set for 454 following the manufacturer’s protocol and deactivating the Bst enzyme at 80°C for 20 min. The libraries were amplified with KAPA HiFi U+ kit, using 10 μl of DNA, 25 μl of KAPA ReadMix (2×), 11 μl of H2O, 1 μl of bovine serum albumin (2.5 mg/ml), and 1.5 μl of the IS5 and IS7 primers (each). The thermocycler program was as follows: initial denature at 95°C for 5 min, (98°C for 20 s, 60°C for 15 s, and 72°C for 30 s) for X cycles, final extension at 72°C for 5 min, and hold at 4°C. Cycles were determined via quantitative polymerase chain reaction using 1 μl of the preamplified library to determine the amplification curve.

Libraries were constructed from 30 μl of DNA extract

After decontaminating each tooth with bleach and removing the outer layer of cementum, the whole tooth was crushed. The resulting bone powder was predigested in 1 ml of 0.5 M EDTA for 15 min at room temperature (RT) to remove loose contaminants. The supernatant was then removed, and the sample was digested in additional 1 ml of 0.5 M EDTA at RT overnight. One hundred microliters of QIAGEN proteinase K was added to the samples the following day and incubated for 8 hours at 37°C. The supernatant was then removed, and an additional 0.5 m of EDTA was added along with 50 μl of proteinase K for 3 to 5 days, until the powder was no longer mineralized. Silica column–based extraction protocol was then followed as described in (54). DNA was extracted from molars belonging to individuals

used standard ancient DNA extraction methods following stringent guidelines to work with ancient human remains

participants were healthy individuals, over 18 years of age, and gave their informed consent

all samples were collected by indigenous representatives and/or local researchers. For the Aymara population, the samples were collected by E. Vargas Pacheco and M. Villena, two representatives of the Aymara community. The Huilliche-Pehuenche samples correspond to a historical collection of modern DNA samples at the Program of Human Genetics of the University of Chile

The collapse difference between high- and low-altitude populations from the Andes region is significant

We infer a split between low- and high-altitude populations in the Andes occurring at 8750 years

27% reduction in effective population size and occurring 425 years ago

Both the Rio Uncallane and K1 trace their genetic ancestry to a single component (shown in red), which is also shared by the modern Andean populations of the Quechua and the Aymara

Principal components analysis reveals a tight clustering of the Rio Uncallane and Kaillachuro (K1) individuals, which overlays with modern Andean populations

Outgroup ƒ3 statistics of a worldwide dataset demonstrate that all seven ancient individuals from all three time periods display greater affinity with Native American groups than with other worldwide populations (Fig. 1). Ranked outgroup ƒ3 statistics suggest that the ancient individuals from all three time periods tend to share the greatest affinity with Andean living groups (Fig. 1A)

revealed that all the modern samples had trivial amounts of nonindigenous ancestry (less than 5%).

exhibited the highest endogenous DNA proportion among burials from the same site (3.15%), and sequenced to an average read depth of 3.92×

The samples from the Rio Uncallane site showed the highest endogenous content

before the present (BP)

first assess the genetic affinities of the prehistoric individuals and compare them to modern South Americans and other ancient Native Americans. Second, we construct a demographic model that estimates the timing of the lowland-highland population split as well as the population collapse following European contact, and last, we explore evidence for genetic changes associated with selective pressures associated with the permanent occupation of the highlands, the intensification of tuber usage, and the impact of European-borne diseases.

compare the genomes of these ancient individuals to 25 new genomes and 39 new genome-wide single-nucleotide polymorphism (SNP) datasets generated from two modern indigenous populations: the Aymara of highland Bolivia and the Huilliche-Pehuenche of coastal lowland Chile.

collected a time series of ancient whole genomes from individuals in the Lake Titicaca region of Peru (fig. S1 and Table 1). The series represents three different cultural periods, which include individuals from (i) Rio Uncallane, a series of cave crevice tombs dating to ~1800 BP and used by fully sedentary agriculturists, (ii) Kaillachuro, a ~3800-year-old site marked by the transition from mobile foraging to agropastoralism and residential sedentism, and (iii) Soro Mik’aya Patjxa (SMP), an 8000- to 6500-year-old site inhabited by residentially mobile hunter-gatherers

selective pressure on the human genome was likely strong–not only because of challenging environmental factors, but also because social processes such as intensification of subsistence resources and residential sedentism (7) promoted the development of agricultural economies, social inequality, and relatively high population densities across much of the highlands.

split between low- and high-elevation populations that occurred between 9200 and 8200 BP; a population collapse after European contact that is significantly more severe in South American lowlanders than in highland populations; and evidence for positive selection at genetic loci related to starch digestion and plausibly pathogen resistance after European contact.

ancient whole genomes from the Andes of Peru, dating back to 7000 calendar years before the present (BP), and compare them to 42 new genome-wide genetic variation datasets from both highland and lowland populations

Overall,decreased genetic diversity within and increasedgenetic differentiation between urban popula-tions are the most commonly reported patternsof urban evolution

Standing genetic variation is more likelythan new mutations to result in rapid adaptiveand nonadaptive evolution in response to urban-ization

Evolution from new mutations occurs over muchlonger time scales than the process of urbaniza-tionandisthusunlikelytoresultinsubstantialchange in response to urbanization on its own.

Does urbanization affect evolution?

urbanization frequently af-fects adaptive (natural and sexual selection) andnonadaptive (genetic drift and gene flow) evolu-tionary processes in organisms

Rats,pigeons,bedbugs,andcockroachesarejust a few of the examples of organisms that haveadapted to live in and around human settlements

convergent environments, in which distant citiesaremoresimilartooneanotherthanurbanareasare to their surrounding nonurban environments

Some of theclearest changes to the physical environmentcaused by urbanization involve increased im-pervious surface cover (such as buildings androads), higher temperatures, as well as elevatedair, noise, and light pollution

Fifty-five percent of people live in cities (1), with urbanareas comprising 3% of Earth’slandsurface(

Urbanizationis the process by which humans formdense settlements constructed of build-ings,roads,andsupportinginfrastructure

Despite advances in urban ecology, we do not adequately understand howurbanization affects the evolution of organisms, nor how this evolution may affect ecosystemsand human health

A smallnumber of studies suggest that industrial pollu-tion can elevate mutation rates,

Some of the clearest resultsof urban evolution show that cities elevate thestrength of random genetic drift (stochasticchanges in allele frequencies) and restrict geneflow (the movement of alleles between popula-tions due to dispersal and mating).

Despite our tremendous success so far, there remains much to be accomplished. Here, we suggest the following 5 areas in which we see a pressing need for additional research:

Why the ornaments used by birds and other nonhuman animals usually appear so strikingly beautiful to humans is another question, but it’s a mystery that does not have to be solved for us to understand sexual selection.

such a genetic correlation will allow a female to produce higher-fitness offspring by choosing males with better ornaments, and hence female choice will evolve

Darwin clearly understood that female preferences existed, but he never compellingly explained why such preferences would evolve

But why would female preferences exist in the first place? The answer to this question is not entirely obvious.

Darwin (1871) correctly realized that sexual selection could be mediated by male-male combat or by a female’s choice of attractive males.

The second theme is related to the question of why sexual selection is strong in some lineages but not others

precopulatory sexual selection, so a more complete definition should also include postcopulatory processes

“sexual selection arises from differences in reproductive success caused by competition for access to mates”

We are, however, here concerned only with that kind of selection, which I have called sexual selection. This depends on the advantage which certain individuals have over other individuals of the same sex and species, in exclusive relation to reproduction.

but many of Darwin’s insights regarding sexual selection appear in his chapters on humans.

One of the great strengths of Darwin was that he often constructed his literary works with a clear argument in mind and marshaled vast amounts of evidence to support his case.

However, a review of the literature shows that key aspects of sexual selection are still plagued by confusion and disagreement. Many of these areas are complex and will require new theory and empirical data for complete resolution.

Thus the larger genera tend to become larger; and throughout nature the forms of life which are now dominant tend to become still more dominant by leaving many modified and dominant descendants. But, by steps hereafter to be explained, the larger genera also tend to break up into smaller genera. And thus, the forms of life throughout the universe become divided into groups subordinate to groups.

Finally, varieties cannot be distinguished from species--except, first, by the discovery of intermediate linking forms; and, secondly, by a certain indefinite amount of difference between them; for two forms, if differing very little, are generally ranked as varieties, notwithstanding that they cannot be closely connected; but the amount of difference considered necessary to give to any two forms the rank of species cannot be defined

In this respect, therefore, the species of the larger genera resemble varieties, more than do the species of the smaller genera.

Hence the amount of difference is one very important criterion in settling whether two forms should be ranked as species or varieties

And this, perhaps, might have been anticipated; for, as varieties, in order to become in any degree permanent, necessarily have to struggle with the other inhabitants of the country, the species which are already dominant will be the most likely to yield offspring, which, though in some slight degree modified, still inherit those advantages that enabled their parents to become dominant over their compatriots.

But cases of great difficulty, which I will not here enumerate, sometimes arise in deciding whether or not to rank one form as a variety of another, even when they are closely connected by intermediate links; nor will the commonly assumed hybrid nature of the intermediate forms always remove the difficulty. In very many cases, however, one form is ranked as a variety of another, not because the intermediate links have actually been found, but because analogy leads the observer to suppose either that they do now somewhere exist, or may formerly have existed; and here a wide door for the entry of doubt and conjecture is opened.

The forms which possess in some considerable degree the character of species, but which are so closely similar to other forms, or are so closely linked to them by intermediate gradations, that naturalists do not like to rank them as distinct species, are in several respects the most important for us

Genera which are polymorphic in one country seem to be, with a few exceptions, polymorphic in other countries, and likewise, judging from Brachiopod shells, at former periods of time. These facts are very perplexing, for they seem to show that this kind of variability is independent of the conditions of life

. These individual differences are of the highest importance for us, for they are often inherited, as must be familiar to every one; and they thus afford materials for natural selection to act on and accumulate, in the same manner as man accumulates in any given direction individual differences in his domesticated productions

The many slight differences which appear in the offspring from the same parents, or which it may be presumed have thus arisen, from being observed in the individuals of the same species inhabiting the same confined locality, may be called individual differences

Generally the term includes the unknown element of a distinct act of creation.

Variability -- Individual differences -- Doubtful species -- Wide ranging, much diffused, and common species, vary most -- Species of the larger genera in each country vary more frequently than the species of the smaller genera -- Many of the species of the larger genera resemble varieties in being very closely, but unequally, related to each other, and in having restricted ranges.

Models of mutation, inheritance, and selection have inspired the development of computational evolutionary algorithms that are used to solve complex problems in many fields [53],[54]. In particular, engineering and design processes have incorporated evolutionary computation, leading to improvements in design of cars, bridges, traffic systems robots, and wind turbine energy, among other applications

prediction of diseases that may emerge from recent host-shifts to humans [33]; discovery, design, and enhancement of drugs and vaccines

diabetes and autoimmune diseases such as asthma may represent mismatches between evolutionary adaptation to the environments in which humans evolved and current conditions.

Much human activity, however, is changing Earth's climate and habitats, with uncertain but potentially severe environmental stresses on many other species [15]–[18], and the solutions to the many resulting problems may well require understanding evolutionary interactions among species and their mutual dependencies.

develop better crops to feed the world, understand and sustain ecosystem function and biodiversity in a changing world, expand sustainable alternative energy sources, and understand individual health.

And the impact of evolutionary biology is extending further and further into biomedical research and nonbiological fields such as engineering, computer sciences, and even the criminal justice system.