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DNA adaptation in human life

DNA adaptation in human life


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Does our DNA adapt by human lifetime? Or do we have the same genetic information from birth to death? I mean: What is usually called "evolution" means "natural selection" like this: http://www.youtube.com/watch?v=hOfRN0KihOU&list=UUsXVk37bltHxD1rDPwtNM8Q -stronger animals have more descendants, so they make bigger percent of strong animals. But does evolution work by some primitive genetics-engineering too? Thank you.


Lewontin's recipe

A very nice way to consider natural selection is through the lense of Lewontin's recipe. Evolution of a given trait (tail length for example) through natural selection occurs whenever the three following conditions are met:

  1. There is variation for this trait in the population
    • This variation is caused by mutations
  2. Part (or the totality) of this variation is heritable
    • Heritability is the part of the variance in a trait that is explained by genes. It can be measured as a parent-offspring correlation.
  3. The variation of this trait is correlated with fitness
    • loosely speaking, fitness is an index of both fecundity and survival

You can take two minutes to think about how logical it is that changes in frequency of variants (natural selection) occurs whenever these three conditions are met. You can imagine any objects you want (pencils of colors for example) and simulate these three steps:

  1. Variation
    • different pencils have different colors
  2. Heritability
    • simulate that your pencils reproduce (asexual reproduction is conceptually easier to understand) and offsprings have similar (or even the same) color than parents
  3. Correlation between trait and fitness
    • Pencils of different colors have different fitness.
    • For example each red pencils create two red pencils the next generation while blue pencils do not manage to replicate at all.

You can quickly see how the red pencils become more frequent in your pencil population through time. If you wait long enough your pencil population will be totally composed of red pencils. And you'll need to simulate a mutation in order to create a blue pencil. I think you understand the how different are the roles of mutations and natural selection in evolution with this example.


Genetic Adaptation During Lifetime of a multicellular organism

For a beginner in evolutionary biology, saying that a multicellular individual's genome does not change during its lifetime might be considered satisfying. In reality it is slightly more complicated. Two elements that are mostly influent very early in the lifetime of an individual have to be considered.

  1. While most mutations occurs during reproduction, some mutations does also occurs during body growth or stated differently during cell reproduction (Mitosis). In consequence, some pairs of your cells share exactly the same genome while other pairs of cells have a sligthly different genome.

  2. Moreover, once some mutations had occurred within the development of an individual, these mutations might influence the fitness of the cells and therefore some alleles (variant of a gene) might raise in frequency while others decrease in frequency (Natural selection). It is important to understand that this process of natural selection select for cells that have a higher fitness and therefore do not necessarily select for the cells that allows the individual to increase its own fitness.


I don't fully understand what you mean when saying: "But does evolution work by some primitive genetics-engineering too?" Could you try to rephrase this question?

Please, let me know if I answered your question!


Note:

Here is a good way to understand the difference between "gene" and "allele". A gene might be a called the "eyes color" gene for example, while the three alleles of the "eyes color" gene might be callsed "blue eyes", "brown eyes" and "green eyes". In this sense, the alleles are the different variants of a gene. Mutations increase the number of alleles and natural selection reduces the number of alleles by selecting for the allele that cause its holder to have the greatest fitness. If you understood that, it is already good!

Note: Natural selection does not necessarily reduce the number of alleles, several alleles might be kept (polymorphism) in certain "types" of natural selection (frequency dependent selection and overdominance (heterozygote advantage), fitness varies in space and/or time, selection acts on different levels). The "type" of Natural selection that reduces the number of alleles after some time is called directional selection.


The concept that the environment directly changes DNA and alters the characteristics of the offspring falls under the heading of Lamarkism. In the context of DNA the Lamarkian view would be that the giraffe got its long neck by stretching its neck cells reaching up to tall trees for leaves, which then (somehow) changed the DNA in its gametes and thus produced offspring with longer necks. There's no compelling evidence for Lamarkism and Remi.b 's nice answer describes DNA and evolution/selection/adaptation in its standard form and how giraffes would evolve such features.

OP initially asked 'does our DNA adapt during our lifetime'. Certain regions of the DNA in each of our immune T-cells and B-cells change (recombine) to code for specific protein molecules that bind to antigens. These are the genes for the T-cell receptor in T-cells and antibodies in the case of B-cells. So the DNA in a T-cell or B-cell is different compared to other cells in the body including the gametes. These regions of altered DNA help us fight infection.

You can easily imagine that an individuals ability to fight infection may affect whether they can survive to reproductive age. Genes involved in immune system function might be selected for during deadly epidemics. And paradoxically, some genes responsible for debilitating or deadly diseases can persist in human society due to their protective effect against other diseases.

For completeness there is also some emerging data that neurons have some alterations in their DNA but its not clear what, if anything, that means and whether its of functional significance. Unless similar types of changes are made in gametes, DNA altered by this mechanism will not be passed on to offspring.

Finally, DNA in cells can be modified by a process called epigenetics. Epi- means 'around'. In epigenetics various regions of the DNA strand (and some related proteins that keep DNA coiled up called histones) are chemically modified by a set of enzymes. Epigenetics affects how certain genes are switched on and off and is perhaps best known for inactivating one of the two X chromosomes in female cells. In epigenetic modifications the DNA sequence remains the same but the epigenetic 'decorations' around the DNA can vary and this process can be influenced by the cells environment.


Effect of stress on human biology: Epigenetics, adaptation, inheritance, and social significance

I present a brief introduction to epigenetics, focused primarily on methylation of the genome and various regulatory RNAs, modifications of associated histones, and their importance in enabling us to adapt to real and changing environmental, developmental, and social circumstances. Following this is a more extensive overview of how it impacts our inheritance, our entire life (which changes as we age), and how we interact with others. Throughout, I emphasize the critical influence that stress, of many varieties exerts, via epigenetic means, on much of how we live and survive, mostly in the brain. I end with a short section on multigenerational transmission, drugs, and the importance of both social life and early life experiences in the development of adult diseases. There will be nothing about cancer. Although epigenetics is critical in that field, it is a whole different cobweb of complications (some involving stress).

Keywords: drugs early life experiences epigenetics social life stress.


Human genetic adaptations and human variation

Skin color

Click on this link to watch a fantastic video explaining the interplay of skin color, UV, and vitamin D.

Body size and shape

There are two ecological rules, known as Bergmann’s rule and Allen’s rule, that explain the variation in size and shape of bodies and extremities using latitude and temperature.

Bergmann’s rule: Warm-blooded animals tend to have increasing body size with increasing latitude (toward the poles) and decreasing average temperatures.

Allen’s rule: A corollary of Bergmann’s rule that applies to appendages. Warm-blooded animals tend to have shorter limbs with increasing latitude and decreasing average temperatures.

When organisms are more compact, they tend to conserve heat (due to a high mass:surface area ratio). When organisms are more linear, they tend to lose more heat (due to a low mass:surface area ratio).

This has been applied to humans. The idea is that populations toward the pole tend to be shorter and have shorter limbs than do people on the equator.

For example, the Inuit people of Canada (pictured above) tend to be shorter than the Maasai people of Kenya (pictured below):


Human evolution is still happening – possibly faster than ever

Yes, we’re still evolving. Credit: watchara/Shutterstock

Modern medicine's ability to keep us alive makes it tempting to think human evolution may have stopped. Better healthcare disrupts a key driving force of evolution by keeping some people alive longer, making them more likely to pass on their genes. But if we look at the rate of our DNA's evolution, we can see that human evolution hasn't stopped – it may even be happening faster than before.

Evolution is a gradual change to the DNA of a species over many generations. It can occur by natural selection, when certain traits created by genetic mutations help an organism survive or reproduce. Such mutations are thus more likely to be passed on to the next generation, so they increase in frequency in a population. Gradually, these mutations and their associated traits become more common among the whole group.

By looking at global studies of our DNA, we can see evidence that natural selection has recently made changes and continues to do so. Though modern healthcare frees us from many causes of death, in countries without access to good healthcare, populations are continuing to evolve. Survivors of infectious disease outbreaks drive natural selection by giving their genetic resistance to offspring. Our DNA shows evidence for recent selection for resistance of killer diseases like Lassa fever and malaria. Selection in response to malaria is still ongoing in regions where the disease remains common.

Humans are also adapting to their environment. Mutations allowing humans to live at high altitudes have become more common in populations in Tibet, Ethiopia, and the Andes. The spread of genetic mutations in Tibet is possibly the fastest evolutionary change in humans, occurring over the last 3,000 years. This rapid surge in frequency of a mutated gene that increases blood oxygen content gives locals a survival advantage in higher altitudes, resulting in more surviving children.

Diet is another source for adaptations. Evidence from Inuit DNA shows a recent adaptation that allows them to thrive on their fat-rich diet of Arctic mammals. Studies also show that natural selection favouring a mutation allowing adults to produce lactase – the enzyme that breaks down milk sugars – is why some groups of people can digest milk after weaning. Over 80% of north-west Europeans can, but in parts of East Asia, where milk is much less commonly drunk, an inability to digest lactose is the norm. Like high altitude adaptation, selection to digest milk has evolved more than once in humans and may be the strongest kind of recent selection.

We may well be adapting to unhealthy diets too. One study of family genetic changes in the US during the 20th century found selection for reduced blood pressure and cholesterol levels, both of which can be lethally raised by modern diets.

Yet, despite these changes, natural selection only affects about 8% of our genome. According to the neutral evolution theory, mutations in the rest of the genome may freely change frequency in populations by chance. If natural selection is weakened, mutations it would normally purge aren't removed as efficiently, which could increase their frequency and so increase the rate of evolution.

Evolution explains why we can still drink milk. Credit: Valerii__Dex/Shutterstock

But neutral evolution can't explain why some genes are evolving much faster than others. We measure the speed of gene evolution by comparing human DNA with that of other species, which also allows us to determine which genes are fast-evolving in humans alone. One fast-evolving gene is human accelerated region 1 (HAR1), which is needed during brain development. A random section of human DNA is on average more than 98% identical to the chimp comparator, but HAR1 is so fast evolving that it's only around 85% similar.

Though scientists can see these changes are happening – and how quickly – we still don't fully understand why fast evolution happens to some genes but not others. Originally thought to be the result of natural selection exclusively, we now know this isn't always true.

Recently attention has focused on the process of biased gene conversion, which occurs when our DNA is passed on via our sperm and eggs. Making these sex cells involves breaking DNA molecules, recombining them, then repairing the break. However, molecular repairs tend to happen in a biased manner.

DNA molecules are made with four different chemical bases known as C, G, A and T. The repair process prefers to make fixes using C and G bases rather than A or T. While unclear why this bias exists, it tends to cause G and C to become more common.

Increases in G and C at DNA's regular repair sites causes ultrafast evolution of parts of our genome, a process easily mistaken for natural selection, since both cause rapid DNA change at highly localised sites. About a fifth of our fastest evolving genes, including HAR1, have been affected by this process. If the GC changes are harmful, natural selection would normally oppose them. But with selection weakened, this process could largely go unchecked and could even help speed up our DNA's evolution.

The human mutation rate itself may also be changing. The main source of mutations in human DNA is the cell division process that creates sperm cells. The older males get, the more mutations occur in their sperm. So if their contribution to the gene pool changes – for example, if men delay having children – the mutation rate will change too. This sets the rate of neutral evolution.

Realising evolution doesn't only happen by natural selection makes it clear the process isn't likely to ever stop. Freeing our genomes from the pressures of natural selection only opens them up to other evolutionary processes – making it even harder to predict what future humans will be like. However, it's quite possible that with modern medicine's protections, there will be more genetic problems in store for future generations.

This article is republished from The Conversation under a Creative Commons license. Read the original article.


3. Current Research Progress

Recombinant DNA technology is a fast growing field and researchers around the globe are developing new approaches, devices, and engineered products for application in different sectors including agriculture, health, and environment. For example, Lispro (Humalog), in comparison with regular human insulin, is a well effective and fast acting recombinant insulin [3]. Similarly, Epoetin alfa is a novel and well-recognized recombinant protein that can be effectively used in curing of anemia [22]. Recombinant hGH was found with a great improvement in treating children lacking the ability to produce hGH in a required quantity. Clinical testing approval by the FDA in December 1997 for a recombinant version of the cytokine myeloid progenitor inhibitory factor-1 (MPIF-1) was an achievement to give recognition to this technology. With its help anticancer drug's side effects can be mitigated whereas it has the ability to mimic the division of immunologically important cells [23, 24]. The following section summarizes the most recent developments of recombinant DNA technology.

Clustered regularly interspaced short palindromic repeats (CRISPR), a more recent development of recombinant DNA technology, has brought out solutions to several problems in different species. This system can be used to target destruction of genes in human cells. Activation, suppression, addition, and deletion of genes in human's cells, mice, rats, zebrafish, bacteria, fruit flies, yeast, nematodes, and crops proved the technique a promising one. Mouse models can be managed for studying human diseases with CRISPR, where individual genes study becomes much faster and the genes interactions studies become easy by changing multiple genes in cells [25]. The CRISPR of H. hispanica genome is capable of getting adapted to the nonlytic viruses very efficiently. The associated Cas operon encodes the interfering Cas3 nucleases and other Cas proteins. The engineering of a strain is required with priming CRISPR for priming crRNAs production and new spacers acceptance. CRISPR-cas system has to integrate new spacers into its locus for adaptive immunity generation [26]. Recognition of foreign DNA/RNA and its cleavage is a controlled process in sequence-specific manner. Information related to the intruder's genetic material is stored by the host system with the help of photo-spacer incorporation into the CRISPR system [27]. Cas9t (gene editing tool) represents DNA endonucleases which use RNA molecules to recognize specific target [28]. Class 2 CRISPR-Cas system with single protein effectors can be employed for genome editing processes. Dead Cas9 is important for histone modifying enzyme's recruitment, transcriptional repression, localization of fluorescent protein labels, and transcriptional activation [29]. Targeting of genes involved in homozygous gene knockouts isolation process is carried out by CRISPR-induced mutations. In this way, essential genes can be analyzed which in turn can be used for “potential antifungal targets” exploration [30]. Natural CRISPR-cas immunity exploitation has been used for generation of strains which are resistant to different types of disruptive viruses [31].

CRISPR-Cas, the only adaptive immune system in prokaryotes, contains genomic locus known as CRISPR having short repetitive elements and spacers (unique sequences). CRISPR array is preceded by AT-rich leader sequence and flanked by cas genes which encode Cas proteins [32, 33]. In Escherichia coli cas1 and cas2 catalases promote new spacers through complex formation. Photo-spacer adjacent motif (PAM) is required for interference and acquisition because the target sequence selection is not random. The memorization of the invader's sequence starts after CRISPR array transcription into long precursor crRNA. During the final stages of immunity process, target is degraded through interference with invaded nucleic acids. Specific recognition prevents the system from self-targeting [32, 34]. In different species of Sulfolobus, the CRISPR loci contain multiple spacers whose sequence matches conjugative plasmids significantly while in some cases the conjugative plasmids also contain small CRISPR loci. Spacer acquisition is affected by active viral DNA replication in Sulfolobus species whereas the DNA breaks formation at replication forks causes the process to be stimulated [35]. According to the above information, CRISPR-Cas system has obtained a unique position in advanced biological systems because of its tremendous role in the stability and enhancement of immunity.

Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) are chimeric nucleases composed of programmable, sequence-specific DNA-binding modules linked to a nonspecific DNA cleavage domain. Therapeutic potential of ZFNs and TALENs is more specified and targeted [25, 36, 37]. Similarly, recombinant protein fibroblast growth factor (FGF-1) has been developed which functions in inducing the formation of new blood vessels in myocardium. Its injection (biologic bypass) into a human myocardium cause an increased blood supply to the heart. Apligraf, an FDA approved product, which serves as a recombinant skin replacer, specified for the leg ulcer's treatment and DermaGraft, is effective in the treatment of diabetic ulcers [38�]. After successful production of insulin from E. coli through recombinant DNA technology, currently several animals, notably cattle and pigs, have been selected as insulin producing source, which however, triggered immune responses. The recombinant human insulin is identical to human porcine insulin and comparatively infrequently elicits immunogenic responses. Furthermore, it is more affordable and can satisfy medical needs more readily. Human growth hormone was the first protein expressed in tobacco plants [41, 42]. Besides insulin, several new drugs related to recombinant DNA technology have undergone developmental improvements and a number of protein production systems have been developed. Several engineered microbial strains have been developed to carry out the formulation of drugs [41, 43, 44]. Molecular medicine formation that is specifically based on proteins faces serious issues including methods and biology of the cells which function to produce medically important compounds through recombinant DNA techniques. To overcome these obstacles, there is intense need to improve quality and quantity of medicines based on a molecular phenomenon. Cell factories are considered important in recombinant DNA technologies, but these needed to be explored with more details and in depth as the conventional factories are not fulfilling the needs [42]. Similarly, the endothelial growth factor and Notch signaling were used to engineer oncolytic adenovirus which acts as a breast cancer selective agent for the antagonist's expression. This further, through tumor angiogenesis disruption acts as anticancer agent. This decreases the total blood vessels numbers and causes a dramatic change along with the perfused vessels which indicates the improved efficacy against the tumor and vascular effects [13]. Efforts have been made to modify the influenza virus genome using recombinant DNA technology for development of vaccines. The modifications are based on engineering of vectors to expression of foreign genes. In practical, the NS gene of the influenza virus was replaced with foreign gene, commonly chloramphenicol acetyltransferase gene. Thereafter, the RNA previously recombined is expressed and packaged into virus particles after transfection with purified influenza A virus in the presence of helper virus. It has been clarified that 5′ terminal and the 3′ terminal bases are sufficient from influenza A virus RNA to produce signals for RNA replication, RNA transcription, and RNA packaging into influenza virus [15].

The abovementioned new production systems enhance pipelines for development of various vaccines and drugs and so forth. Production of high quality proteins depends on physiology of a cell and the conditions provided to it. The expression of proteins becomes retarded if a cell goes under stressful conditions, which may also favor the production in some cases. Thus, further improvements are required for the better and safe production at genetic and metabolic levels. Microorganisms are considered the most convenient hosts to produce molecular medicines. These cells allow the incorporation of foreign genes with less resistant barriers and expression is easily controlled. Compared to plant and mammalian cells to be taken as hosts, microbial systems provide less complicated machinery which ultimately enhances the performance and quality of proteins production. The use of common microbial species, including bacteria and yeasts, is promising but the less common strains have also been observed promising as being cellular factories to produce recombinant molecular drugs. The increasing demands of drugs and the needs of quality can be fulfilled with better results if these cellular factories of microorganisms get incorporated into productive processes of pharmaceuticals ( Table 1 ) [41, 45, 46].

Table 1

Current DNA assembly methods for the synthesis of large DNA molecules. The table has been reproduced from Nature reviews 14: 781�, with permission from Nature Publishing Group.

MethodMechanismOverhang (bp)Scar (bp)CommentsExamples of applications
BioBricksType IIP restriction endonuclease88Sequentially assembles small numbers of sequencesConstruction of a functional gene expressing enhanced cyan fluorescent protein
BglBricksType IIP restriction endonuclease66Uses a highly efficient and commonly used restriction endonuclease, the recognition sequences of which are not blocked by the most common DNA methylasesConstruction of constitutively active gene-expression devices and chimeric, multidomain protein fusions
Pairwise selectionType IIS restriction endonuclease654Requires attachment tags at each end of fragments to act as promoters for antibiotic resistance markers rapid, as a liquid culture system is usedAssembly of a 91 kb fragment from 1-2 kb fragments
GoldenGateType IIS restriction endonuclease40Allows large-scale assembly ligations are done in parallel one-step assembly of 2-3 fragmentOne-step assembly of 2-3 fragments
Overlapping PCROverlap00Uses overlapping primers for the PCR amplification of 1𠄳 kb-long fragmentsUsually used for 1𠄳 kb-long fragments, for example, for gene cassette construction
CPECOverlap20�0Uses a single polymerase for the assembly of multiple inserts into any vector in a one-step reaction in vitroOne-step assembly of four 0.17𠄳.2 kb-long PCR fragments
GatewayOverlap200Uses a specific recombinase for small-scale assemblyOne-step assembly of three 0.8𠄲.3 kb-long fragments
USEROverlapUp to 7080Replaces a thymidine with a uracil in the PCR primers, which leaves 3′ overhangs for cloning after cleaving by a uracil exonucleaseOne-step assembly of three 0.6𠄱.5 kb-long fragments
InFusionOverlap150Uses an enzyme mix for parallel assembly through a 𠇌hew-back-and-anneal” methodOne-step assembly of three 0.2𠄳.8 kb-long fragments
SLICOverlap0(i) Uses a T4 DNA polymerase through a chew-back method in the absence of dNTPs
(ii) Uses Recombinase A to stabilize the annealed fragments and avoid in vitro ligation
(iii) Allows the parallel assembly of several hundred base-long fragments
Generation of a ten-way assembly of 300�𠂛p-long PCR fragments
GibsonOverlap40�0Uses enzymatic 𠇌ocktails” to chew back and anneal for the parallel assembly of several kilobase-long fragmentsAssembly of the 1.08 Mb Mycoplasma mycoides JCVI-syn1.0 genome

Tibetans inherited high-altitude gene from ancient human

A “superathlete” gene that helps Sherpas and other Tibetans breathe easy at high altitudes was inherited from an ancient species of human. That’s the conclusion of a new study, which finds that the gene variant came from people known as Denisovans, who went extinct soon after they mated with the ancestors of Europeans and Asians about 40,000 years ago. This is the first time a version of a gene acquired from interbreeding with another type of human has been shown to help modern humans adapt to their environment.

Researchers have long wondered how Tibetans live and work at altitudes above 4000 meters, where the limited supply of oxygen makes most people sick. Other high-altitude people, such as Andean highlanders, have adapted to such thin air by adding more oxygen-carrying hemoglobin to their blood. But Tibetans have adapted by having less hemoglobin in their blood scientists think this trait helps them avoid serious problems, such as clots and strokes caused when the blood thickens with more hemoglobin-laden red blood cells.

Researchers discovered in 2010 that Tibetans have several genes that help them use smaller amounts of oxygen efficiently, allowing them to deliver enough of it to their limbs while exercising at high altitude. Most notable is a version of a gene called EPAS1, which regulates the body’s production of hemoglobin. They were surprised, however, by how rapidly the variant of EPAS1 spread—initially, they thought it spread in 3000 years through 40% of high-altitude Tibetans, which is the fastest genetic sweep ever observed in humans—and they wondered where it came from.

Now, an international team of researchers has sequenced the EPAS1 gene in 40 Tibetans and 40 Han Chinese. Both were once part of the same population that split into two groups sometime between 2750 to 5500 years ago. Population geneticist Rasmus Nielsen of the University of California, Berkeley, his postdoc Emilia Huerta-Sanchez, and their colleagues analyzed the DNA and found that the Tibetans and only two of the 40 Han Chinese had a distinctive segment of the EPAS1 gene in which five letters of the genetic code were identical. When they searched the most diverse catalog of genomes from people around the world in the 1000 Genomes Project, they could not find a single other living person who had the same code.

Then, the team compared the gene variant with DNA sequences from archaic humans, including Neandertals and a Denisovan, whose genome was sequenced from the DNA in a girl’s finger bone from Denisova Cave in the Altai Mountains of Siberia. The Denisovan and Tibetan segments matched closely.

The team also compared the full EPAS1 gene between populations around the world and confirmed that the Tibetans’ inherited the entire gene from Denisovans in the past 40,000 years or so—or from an even earlier ancestor that carried that DNA and passed it on to both Denisovans and modern humans. But they ruled out the second scenario—that the gene was inherited from the last ancestor that modern humans shared with Denisovans more than 400,000 years ago because such a large gene, or segment of DNA, would have accumulated mutations and broken up over that much time—and the Tibetans’ and Denisovans’ versions of the gene wouldn’t match as closely as they do today.

But just how did the Tibetans inherit this gene from people who lived 40,000 years before them in Siberia and other parts of Asia? Using computer modeling, Nielsen and his team found the only plausible explanation was that the ancestors of Tibetans and Han Chinese got the gene by mating with Denisovans. The genome of this enigmatic people has revealed that they were more closely related to Neandertals than to modern humans and they once ranged across Asia, so they may have lived near the ancestors of Tibetans and Han Chinese. Other recent studies have shown that although Melanesians in Papua New Guinea have the highest levels of Denisovan DNA today (about 5% of their genome), some Han Chinese and mainland Asians retain a low level of Denisovan ancestry (about 0.2% to 2%), suggesting that much of their Denisovan ancestry has been wiped out or lost over time as their small populations were absorbed by much larger groups of modern humans.

Although most Han Chinese and other groups lost the Denisovans’ version of the EPAS1 gene because it wasn’t particularly beneficial, Tibetans who settled on the high-altitude Tibetan plateau retained it because it helped them adapt to life there, the team reports online today in Nature. The gene variant was favored by natural selection, so it spread rapidly to many Tibetans.

A few Han Chinese—perhaps 1% to 2%—still carry the Denisovan version of the EPAS1 gene today because the interbreeding took place when the ancestors of Tibetans and Chinese were still part of one group some 40,000 years ago. But the gene was later lost in most Chinese, or the Han Chinese may have acquired it more recently from interbreeding with Tibetans, Nielsen says.

Either way, what is most interesting, Nielsen says, is that the results show that mating with other groups was an important source of beneficial genes in human evolution. “Modern humans didn’t wait for new mutations to adapt to a new environment,” he says. “They could pick up adaptive traits by interbreeding.”

The discovery is the second case in which modern humans have acquired a trait from archaic humans, notes paleogeneticist Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, whose team discovered the Denisovan people. Earlier this year, another team showed that Mayans, in particular, have inherited a gene variant from Neandertals that increases the risk for diabetes.

The ultimate irony, Nielsen notes, is that, once we got this beneficial gene, we never returned the favor. Instead, we may have helped drive the Denisovans extinct.


Advantages of Neanderthal DNA in the Human Genome

Anna Azvolinsky
Nov 10, 2016

WIKICOMMONS, EINSAMER SCHUTZE The interbreeding of Neanderthals and Denisovans with Homo sapiens resulted in advantageous Neanderthal-inherited alleles in the genomes of a diverse range of modern humans, according to genomicists. The team&rsquos analysis, published today (November 10) in Current Biology, expands the number of loci in the human genome attributed to these ancient hominins. The results suggest that these alleles&mdashmostly within immune and skin pigmentation genes&mdashlikely helped modern humans adapt to life outside of Africa.

&ldquoThe study expands our knowledge of the extent to which Neanderthals and Denisovans contributed functionally relevant genetic variation to modern humans,&rdquo Svante Pääbo, an evolutionary geneticist at the Max Planck Institute for Evolutionary Anthropology in Germany, who was not involved in the work, wrote in an email to The Scientist. &ldquoIt shows that the contribution [of hominin DNA] is substantial and is larger than I assumed when we first discovered that these extinct.

“The authors’ approach of rebuilding archaic genomes by mining the remnants from modern genomes is unique and brilliant,” wrote Paul Norman, a senior research scientist at Stanford University in California, in an email to The Scientist. “This study adds to the growing body of evidence that modern humans likely survived better in adapting to new environments through breeding with archaic humans.”

As a result of interbreeding between early hominins, the genomes of people from Europe and Asia contain around 2 percent Neanderthal DNA and those of Melanesian decent have an additional 2 percent to 4 percent from Denisovans. Prior work has mapped some of these inherited loci in the human genome, identifying—among other things—immune genes from Neanderthals, which researchers speculate may have provided both Neanderthals and early H. sapiens adaptive advantages against infectious organisms. Another study using medical records showed that the persistence of Neanderthal DNA in individuals’ genomes was linked to certain clinical traits such as depression.

For the present study, Joshua Akey, an evolutionary and computational biologist at the University of Washington, harnessed diverse human genome sequences and new Neanderthal and Denisovan sequences to create a comprehensive picture of adaptive hominin sequences in the human genome. Akey and colleagues used previously constructed genomic maps of around 1 million Neanderthal and Denisovan sequences previously identified in the genomes of modern humans. The researchers then looked for these loci within the genomes of 1,523 individuals of European, South and East Asian, and Melanesian descent. At a 50 percent false-discovery rate, they found 126 genomic loci where ancient hominin DNA appeared to persist at relatively high frequency among these individuals, indicating that the retained locus is likely to confer an evolutionary advantage.

“What’s nice about this paper is that it generates a comprehensive list of potentially adaptive introgressed loci,” said Tony Capra of Vanderbilt University in Nashville, Tennessee, who was not involved in the work.

While individuals of Melanesian ancestry typically retain mostly Denisovan sequences, in the current analysis, the researchers found that 59 percent of the loci in these individuals were Neanderthal in origin.

The 126 loci—including seven previously identified—corresponded to seven genes involved in skin pigmentation and 31 genes that function in immunity. Each locus had a median length of about 81 kilobases. And 80 percent of the loci mapped to regulatory rather than coding regions. “We know that mutations that modulate gene expression are very important for driving divergence between closely related populations and species. But before this study, it was not clear how often introgressed alleles would exert their effects in this way,” Capra told The Scientist.

Analyzing the expression levels of genes associated with the 126 loci, the team found that 13 of the sites varied the expression of 34 genes across different tissue types. One locus resulted in significantly increased expression of a Toll-like receptor (TLR) gene cluster involved in innate immunity in lymphoblast cell lines, and lower expression in primary B cells and fibroblasts. The team tested whether this differential expression was a result of different levels of innate immune system activation. Using whole blood samples from healthy volunteers, they showed that those individuals with Neanderthal-derived TLR alleles could be specifically activated with a TLR4 agonist within immune cells. “We showed that this effect is specific to activated immune cells, which highlights the challenges in interpreting the effect of sequence variation. If you look in the wrong cell type or time point you would never see the effects,” Akey told The Scientist.

“It’s interesting to see that, like alleles that arise by other evolutionary mechanisms, adaptive introgression appears to commonly influence gene expression,” said Capra.

The results provide new clues about one particular route of human evolution. “Instead of waiting for a new beneficial mutation, we can just pick one up by hybridizing with a population that was already adapted to this new environment,” said Akey. “Finding advantageous genes inherited from archaic humans also shows that hybridization was not just some side note to human history, but had important consequences that we can still see in present day individuals.”

Capra agreed. “We are seeing enough of the signature of introgression in human genomes that we really need to integrate it into our models of evolution and selection.”


Glossary

  1. Theodosius Dobzhansky. “Biology, Molecular and Organismic.” American Zoologist 4, no. 4 (1964): 449. &crarr
  2. Charles Darwin, Journal of Researches into the Natural History and Geology of the Countries Visited during the Voyage of H.M.S. Beagle Round the World, under the Command of Capt. Fitz Roy, R.N, 2nd. ed. (London: John Murray, 1860), http://www.archive.org/details/journalofresea00darw. &crarr
  3. Sahar S. Hanania, Dhia S. Hassawi, and Nidal M. Irshaid, “Allele Frequency and Molecular Genotypes of ABO Blood Group System in a Jordanian Population,” Journal of Medical Sciences 7 (2007): 51-58, doi:10.3923/jms.2007.51.58 &crarr

DNA adaptation in human life - Biology

This book is an adaptation of the CK-12 Foundation textbook “College Human Biology” (which can be found at https://www.ck12.org/book/ck-12-human-biology/) and was authored by Jean Brainard, Ph.D. , Rachel Henderson, Ph.D in 2016. College Human Biology by CK-12 Foundation is licensed as CC BY NC. I would like to wholeheartedly thank Dr. Brainard and Dr. Henderson as well as the CK-12 Foundation for their tremendous work in this area of open educational resources.

The following changes were made to this book as a whole:

  • Canadian spellings were used.
  • Imperial measurements were changed to metric.
  • American statistics and examples were replaced with Canadian statistics and examples.
  • References to American governmental organizations were removed and replaced with Canadian organizations when appropriate.
  • Eurocentric/colonial images were replaced with images more representative of the diversity in student population.
  • Names in case studies were replaced to better represent the diversity in student population.
  • Images and diagrams were replaced with more appealing or higher quality graphics where applicable.
  • The supplementary videos at the end of each section were updated and expanded.
  • A selection of existing review questions were converted to self-marking H5P activities.
  • H5P activities/multimedia were inserted into sections to reinforce concepts.
  • Chapters that did not align with the British Columbia ABE Provincial Level Biology Curriculum were removed.
  • A glossary function was added, which shows definitions when students hover their mouse over a term.
  • The glossary section was expanded to include more vocabulary.
  • Learning objectives, review questions and summaries were colour-coded.
  • The following hyperlinks were created in the text:
    • People of note were linked to their page on Wikipedia.
    • Diseases and disorders were linked to a reliable information page (Mayo Clinic, CDC, etc.).

    The following chapter sections were created or substantially expanded:

    The following additions have been made to these chapters:

    Chapter 3

    Section 3.5: Addition of Cultural Connection: Fats in Tanning

    Chapter 4

    Section 4.4: Inclusion of vaping in the Feature: My Human Body about smoking

    Section 4.10 Addition of transition reaction as an intermediate step in aerobic cellular respiration

    Section 4.11 Addition of paragraph about fermentation in food production

    Section 4.11 Addition of Cultural Connection: Fermentation of Oolichan (candle fish) by Indigenous people in British Columbia

    Chapter 5

    Section 5.3 Addition of Interactive Timeline of Pivotal Events in DNA Research

    Section 5.7 Addition of the paragraph Processing RNA

    Section 5.10 Addition of Cultural Connection: Agricultural Management of Corn by Indigenous People

    Chapter 8

    Section 8.5 Organization of the structures of the brain into the regions of the hindbrain, midbrain and forebrain.

    Section 8.5 Addition of sections on the pons, medulla oblongata, reticular activating system, limbic system, hippocampus, and amygdala.

    Chapter 9

    Section 9.2 Changed introductory paragraph to “Your Body the Chemist”

    Chapter 16

    Section 16.3 Changed introductory paragraph to “Surprising Uses of Pee”

    Chapter 18

    Section 18.8 Addition of paragraph “Bringing It All Together”


    Acknowledgements

    We thank S. Polo and P. Huertas for advice, and K. Dry for expert help with the text and figures. The S.P.J. laboratory is supported by grants from Cancer Research UK, the European Commission (projects GENICA and DNA Repair), the Wellcome Trust and the Biotechnology and Biological Sciences Research Council. The J.B. laboratory is supported by grants from the Danish Cancer Society, the Danish National Research Foundation and the European Commission (projects GENICA, Active p53, TRIREME and DNA Repair).

    Author Contributions S.P.J. and J.B. conceived of and wrote all aspects of this article.


    Watch the video: Biology: Cell Structure I Nucleus Medical Media (October 2022).