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Human Evolutionary Genomics

Submitted by sfairfield on Fri, 05/03/2019 - 06:47

        DNA evidence has dramatically expanded our knowledge of the human evolutionary tree. Since the discovery that genetic material could be recovered from ancient organisms in 1984 (Higuchi et al. 1984), the study of ancient DNA (aDNA) has advanced rapidly. Certain factors can complicate the collection and analysis of aDNA, such as advanced age, the surrounding environment, and the collection technique, which can lead to degradation via cross-linking, deamination of cytosine, and fragmentation, as well as contamination due to extraneous microbial DNA and exposure to modern human DNA during extraction. Despite these difficulties, the revelation that archaic DNA can be sequenced, in conjunction with the sequencing of the human genome less than twenty years later (2001), provided the foundation from which the field of human evolutionary genomics arose. The insights gained about humans closest extinct relatives, Neanderthals and Denisovans, has been particularly impactful. These archaic human populations branched off from the modern lineage early in the Middle Pleistocene, approximately 750,000 years ago, and then separated from each other around 390,000 years ago. Many modern humans carry DNA derived from these archaic populations due to interbreeding during the Late Pleistocene, a period spanning 126,000 to 12,000 years ago (Slon et al. 2018).  In just the last decade, genomes have been recovered from Neanderthals and Denisovans. This has resulted in the determination that Neanderthals account for between 1% and 4% of the ancestry of people outside sub-Saharan Africa (Green et al. 2010), and Denisovans contribute from 1% to 6% of the ancestry of people in island Southeast Asia and Oceania (Meyer et al. 2012). These genomes provide information about the phenotypes of archaic peoples, insight into interactions between them and modern humans, and evidence of their contribution to the biology of modern humans. 

Deep learning Genome Analysis

Submitted by sfairfield on Fri, 05/03/2019 - 01:51

          In Approximate Bayesian computation with deep learning supports a third archaic introgression in Asia and Oceania, the authors use introgressions, defined as the transfer of genetic information from one species to another as a result of hybridization between them and repeated backcrossing, in the human lineage that have been identified using sequenced ancient genomes of Neanderthals and Denisovans to try to identify previously unknown groups. They built a demographic model based on deep learning in an Approximate Bayesian Computation framework to infer the evolutionary history of Eurasian populations including past introgression events in accordance with the current genetic evidence. In addition to the reported Neanderthal and Denisovan introgressions, their results supported a third introgression in all Asian and Oceanian populations from another archaic human population. The authors dubbed this group a “ghost ancestor”, and concluded the population was either related to the Neanderthal-Denisova clade or diverged early from the Denisova lineage. (Mondal et al. 2019)

Hybrid Genome

Submitted by sfairfield on Thu, 05/02/2019 - 20:18

           In The genome of the offspring of a Neanderthal mother and a Denisovan father, the authors analyze the genome of ‘Denisova 11’, a bone fragment from Denisova Cave in Siberia.  They show that it comes from an individual who had a Neanderthal mother and a Denisovan father. The father, whose genome contains traces of Neanderthal ancestry, came from a population related to a later Denisovan found in the cave. The mother came from a population more closely related to Neanderthals who lived later in Europe than to an earlier Neanderthal found in Denisova Cave, indicating 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 allowed the authors to conclude that mixing between Late Pleistocene hominin groups was common when they met. (Slon et al. 2018)

Human Evolutionary Genomics Intro

Submitted by sfairfield on Thu, 05/02/2019 - 17:36

          Neanderthals and Denisovans were archaic human populations that branched off from the modern lineage early in the Middle Pleistocene, approximately 750,000 years ago, and then separated from each other around 390,000 years ago. Many modern humans carry DNA derived from these archaic populations due to interbreeding during the Late Pleistocene, a period spanning 126,000 to 12,000 years ago (Slon et al. 2018). DNA evidence has dramatically expanded our knowledge of the human evolutionary tree. Since the discovery that genetic material could be recovered from ancient organisms in 1984 (Higuchi et al. 1984), the study of ancient DNA (aDNA) has advanced rapidly. Certain factors can complicate the collection and analysis of aDNA, such as advanced age, the surrounding environment, and the collection technique, which can lead to degradation via cross-linking, deamination of cytosine, and fragmentation, as well as contamination due to extraneous microbial DNA and exposure to modern human DNA during extraction. Despite these difficulties, the revelation that archaic DNA can be sequenced, in conjunction with the sequencing of the human genome less than twenty years later (2001), provided the foundation from which the field of human evolutionary genomics arose. In just the last decade, genomes have been recovered from Neanderthals and Denisovans. This has resulted in the determination that Neanderthals account for between 1% and 4% of the ancestry of people outside sub-Saharan Africa (Green et al. 2010), and Denisovans contribute from 1% to 6% of the ancestry of people in island Southeast Asia and Oceania (Meyer et al. 2012). These genomes provide information about the phenotypes of archaic peoples, insight into interactions between them and modern humans, and evidence of their contribution to the biology of modern humans. 

Denisovan Genome

Submitted by sfairfield on Thu, 05/02/2019 - 13:24

          In A High-Coverage Genome Sequence from an Archaic Denisovan Individual, the authors used samples of bone powder from a phalanx fragment found in the  Denisova Cave in the Altai Mountains in southern Siberia. The draft nuclear genome sequence retrieved from the Denisovan phalanx revealed that Denisovans are a sister group to Neandertals, with the Denisovan nuclear genome sequence falling outside Neanderthal genetic diversity, which suggests an independent population history that differs from that of Neanderthals. Also, whereas a genetic contribution from Neanderthal to the present-day human gene pool is present in all populations outside Africa, a contribution from Denisovans is found exclusively in island Southeast Asia and Oceania. To verify this, they sequenced the genomes of 11 present-day individuals: a San, Mbuti, Mandenka, Yoruba, and Dinka from Africa; a French and Sardinian from Europe; a Han, Dai, and Papuan from Asia; and a Karitiana from South America for comparison. They conducted a direct estimation of Denisovan heterozygosity indicating that genetic diversity was extremely low, detailed measurements of Denisovan and Neanderthal admixture into present-day human populations, and generated a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans (Meyer et al. 2012).

Neanderthal/Human hybrids

Submitted by sfairfield on Sat, 04/27/2019 - 18:18

            Neanderthals are thought to have disappeared approximately 39,000–41,000 years ago, but due to overlapping chronologically and geographically with modern humans' ancestors, they contributed 1–3% of the DNA of present-day people in Eurasia. In the study by Fu et al., DNA from a 37,000–42,000-year-old modern human from Peştera cu Oase, Romania was analyzed. Although the specimen contained small amounts of human DNA, an enrichment technique was used to isolate genomic sites that were distinct between Neanderthals and present-day humans. They found that  6–9% of the genome of the Oase individual was derived from Neanderthals, more than any other modern human specimen sequenced to date. Three of the chromosomal segments of Neanderthal ancestry were measured to be over 50 centimorgans in size, indicating that this individual had a Neanderthal ancestor as recently as four to six generations back. However, the Oase individual did not share more alleles with later Europeans than with East Asians, suggesting that the Oase population did not contribute substantially to later humans in Europe.

 

Neanderthal contributions to human genome

Submitted by sfairfield on Sat, 04/27/2019 - 15:45

            Neanderthals are thought to have disappeared in Europe approximately 39,000–41,000 years ago but they have contributed 1–3% of the DNA of present-day people in Eurasia. In the study by Fu et al., DNA from a 37,000–42,000-year-old modern human from Peştera cu Oase, Romania was analyzed. Although the specimen contained small amounts of human DNA, an enrichment strategy was used to isolate sites that were distinct between Neanderthals and present-day humans. They found that on the order of 6–9% of the genome of the Oase individual is derived from Neanderthals, more than any other modern human sequenced to date. Three chromosomal segments of Neanderthal ancestry are over 50 centimorgans in size, indicating that this individual had a Neanderthal ancestor as recently as four to six generations back. However, the Oase individual did not share more alleles with later Europeans than with East Asians, suggesting that the Oase population did not contribute substantially to later humans in Europe.

Future of aDNA

Submitted by sfairfield on Fri, 04/26/2019 - 12:45

          Ancient DNA has enabled us to answer long-standing questions about the relationship between archaic and modern humans. Admixture among archaic groups and between them and modern humans seems to have occurred whenever they came into geographic proximity. In that way, they were no different from groups of modern humans. Although most present-day human ancestry can be traced to African populations that dispersed into Eurasia ∼100,000 y ago, aDNA has allowed us to also determine which parts of our genomes are from archaic hominins that occupied Eurasia before modern humans. All non-African genomes carry small amounts of Neanderthal ancestry, and some carry an additional component of Denisovan ancestry. Because the paleoanthropological record of much of Asia is relatively poorly known, it is likely that more Neanderthal and Denisovan fossils will be found in this region. It is even possible that additional extinct groups of hominins will be identified using aDNA.

Ancient DNA

Submitted by sfairfield on Fri, 04/26/2019 - 11:20

          The first study of what would come to be called aDNA was conducted in 1984, when Russ Higuchi and colleagues at the University of California, Berkeley reported that traces of DNA from a museum specimen of the Quagga not only remained in the specimen over 150 years after the death of the individual, but could be extracted and sequenced. To determine whether DNA survives and can be recovered from the remains of extinct creatures, they examined dried muscle from a museum specimen of the quagga, a zebra-like species endemic to South Africa that went extinct in 1883. Over the next two years, through investigations into natural and artificially mummified specimens, researchers confirmed that this phenomenon was not limited to relatively recent museum specimens but could apparently be replicated in a range of mummified human samples that dated as far back as several thousand years.

 

Esterification

Submitted by sfairfield on Sat, 04/13/2019 - 14:56

          In this experiment, the goal was to synthesize 3-methylbutyl acetate and utilize several characterization methods to verify the successful formation of the product. The reaction was performed via esterification, using acetic acid and 3-methyl-1-butanol as reagents and sulfuric acid as the catalyst. The odor of acetic acid resembled that of vinegar, while the odor of 3-methyl-1-butanol resembled an artificial sour apple smell. The odor of the product, 3-methylbutyl acetate, resembled an artificial banana smell. This indicates that the product was successfully synthesized because 3-methylbutyl acetate is known informally as banana oil. The percent yield of the product was 84.42%. The low yield could have been a result of transfer loss from some product remaining in the reflux column. A sample of the product was used to allow for further identification via IR spectroscopy. The IR displayed an alkyl C-H stretch at 2959.90 cm-1 and a C=O stretch at 1741.80 cm-1, as well as no large absorptions above 3000 cm-1, indicating that there are no O-H containing impurities. These experimental data are consistent with the known  IR spectrum of a typical alkyl ester, which is characterized by an alkyl C-H stretch that is just to the right of 3000 cm-1 and a C=O stretch that is at about 1750 cm-1. This supports the conclusion that 3-methylbutyl acetate was successfully synthesized.

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