The mitochondria.
Mitochondria and Mitochondrial DNA
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The mitochondria.
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Written by: Annemarie Nagle
Mitochondria are organelles found in virtually all eukaryotic cells. These organelles are the sites of cellular respiration and thereby earn the nickname "powerhouse of the cell". Cells typically contain hundreds to thousands of mitochondria.
Where did mitochondria come from?
According to popular theory, mitochondria originated from small, aerobic prokaryotes living within larger cells as undigested prey or internal parasites. A symbiotic relationship eventually developed as the anaerobic host cells became increasingly dependent on the internalized aerobic bacteria for energy production due to the earth’s atmosphere becoming increasingly saturated with oxygen. Mitochondria are the appropriate size to be descendants of bacteria and their inner membranes contain several enzymes and proteins resembling those found in modern prokaryotes.
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Mitochondria exist in the cytoplasm and mtDNA exist in the matrix of the mitochondria. |
What is mitochondrial DNA?
Mitochondria, unlike most other organelles, contain their own distinct genome. This mitochondrial DNA (mtDNA) exists in a single circular DNA molecule, similar to prokaryotic genomes. Mitochondria reproduce by a process reminiscent of bacterial binary fission, resulting in the exact duplication of the genome. Unlike the DNA contained within cell nuclei, mtDNA is not recombinant, that is, it is not a combination of the parents’ DNA but rather, an exact copy of one.
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The mitochondrial chromosome exists as a single circular DNA molecule |
How is mtDNA inherited?
Mitochondrial DNA is passed from generation to generation along the maternal lineage. Females in a family have cells containing identical mtDNA. At conception, the relatively enormous egg contains around 100,000 mitochondria compared to the 50-100 contained within the tiny sperm. When the egg is fertilized, very few mitochondria from the male survive, and those that do are actively eliminated. The embryo thus inherits mitochondria?and subsequently mitochondrial DNA?from only the mother. This constant path of inheritance makes mtDNA a prime candidate for molecular genealogy and anthropology.
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How do changes in mtDNA occur?
Changes in mtDNA occur through mutations called single nucleotide polymorphisms, or SNPs. These mutations are typically due to simple copying errors or radiation damage to the DNA. The mutation rate of mtDNA is relatively high in comparison to nuclear DNA due to the much higher rate of DNA duplication in the mitochondria and the fact that each cell contains many of these organelles.
How can these mutations be used in dating?
Over time, the SNPs accumulate in the mitochondrial DNA as they are passed on through the maternal lineage. As lines of inheritance and populations diverge, the separate paths develop their own distinctive sets of mutations. To attribute actual times or points of divergence to these mutations, systematists and molecular anthropologists use mechanisms called molecular clocks. These clocks are calibrated by comparing current mtDNA to that of fossils from a known date. This then allows scientists to determine an approximate rate of mutation, which in turn tells them the relative age of the sample in question. The fact that the mutation rate is quite high increases the probability for the incidence of back mutations, where a mutation that has already occurred in the DNA changes back to its original state. Thus, the observed number of mutations itself does not account for all the mutations that have occurred throughout the history of the species, and this must be taken into consideration when assigning dates to events.
How can these mutations be used to determine ancestry?
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Using the same biologicalclocks used in dating, scientists can determine how closely related two individuals are. By comparing the differences in the mtDNA of the individuals it is possible to calculate the approximate date of the most recent common ancestor (MRCA). This technique is used to determine when populations have diverged in the past and anthropologists use mtDNA analysis to track the migration of populations throughout history. In 1987 a research team from the University of California ? Berkeley determined that the entire existing human population is descendent from an African woman who lived approximately 150,000 years ago dubbed "mitochondrial Eve." All of the existing mitochondrial DNA lineages in the modern world branch out from this Eve and each branch is called a haplogroup. These haplogroups represent populations of individuals with slowly changing sections of similarity in their mtDNA. An individual’s haplogroup therefore tells which "daughter of Eve" they descended from. As many of the initial mutations in the mtDNA of the daughters of Eve were occurring, large migrations were happening simultaneously, making some changes unique to certain regions of the world. Haplogroups are then further divided into haplotypes, which are relatively quickly changing DNA similarities. By studying haplotypes, the branching and movement of populations can be traced with a greater degree of precision.
Mitochondrial Eve
Who was she?
This is often a topic of much confusion. Eve was not the first human, and would not necessarily have had to have any more than one female child who lived to reproduce. She would have had many ancestors, and she and the people that she lived among would have been preceded by many mitochondrial Eves before her; this woman was simply our most recent common ancestor.
This woman is believed by population geneticists to have been a member of an original human population comprised of only about 2,000 interbreeding individuals. The mtDNA record does not reflect the existence of these other individuals, however, and it is believed that the lineages begot by the other females in the world at the time have all become extinct.
How do we all share her mtDNA?
The genetic evidence suggests that there was a genetic bottleneck at the time that Eve lived. A bottleneck would have been the result of some catastrophic event in the time period that would have so drastically reduced the numbers of the human population that this single woman’s DNA would have had a significant potential for expression in the subsequent generations. It is quite likely that to survive such a crisis and pass along her genetic material, Eve would have had to be a member of a population that was isolated from the catastrophic event, or have had traits that made her and her offspring better able to endure the conditions.
How has mtDNA been used in anthropology? Here are just a few examples:
Indian Ancestry
A remarkable study performed in 2001 by Michael Bamshad and a team of researchers from the University of Utah led to the conclusion that the members of the Indian upper and lower classes have different origins; the upper classes are genetically more related to Europeans than are the lower classes, which have stronger Asian ties. The study also indicates that Indian women enjoy a higher level of social mobility within the strict Indian caste system than do the men.
The Utah team analyzed genetic material from 250 individuals for the study, and placed them, according to their social class, into three categories. The "lower" class grouping was comprised of Relli, Madig and Mala; the "middle" class included Kapu, Yadava, Jalari and Madabahija; the "upper" class encompassed Brahmin, Kshatriyas and Vysyas. From here the scientists compared the genetic makeup of the individuals from varying classes using mtDNA and Y chromosome analysis.
The mtDNA analysis turned up 152 unique haplotypes within the samples, and comparison among the three categories revealed that four of the unique clusters are shared between the upper middle class and the lower classes, seven are shared between the lower and middle classes, and three haplotypes are unique to the middle and upper classes. The team discovered no shared haplotypes between the upper and lower classes. Due to the matrilineal inheritance of the mtDNA, these findings seem to be direct indicators of the movements of women within the Hindu classes. Bamshad believes that the results demonstrate
circumstances in which a woman can occasionally marry a man from a higher social class, passing her mtDNA on to children whom would be of her husband’s social rank. Analysis of the Y chromosome produced very similar results for the genetic distances between classes, but also demonstrated a smaller margin of difference between the middle and lower castes. The mitochondrial evidence also indicates that women from all of the classes are more closely related genetically to Asians as opposed to Europeans, but the upper castes do not appear to be as distantly related to Europeans as their lower counterparts.
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While the mtDNA evidence shows that Indian women are overall more closely related to Asians than Europeans, the Y chromosome analysis indicates the opposite for men. The Y chromosome evidence placed all men within the caste system genetically closer to Europeans, with the similarities more apparent in the upper and upper middle classes. This evidence has been used to confirm historical reports that the West Eurasian immigrants who have come to India within the past 10,000 years have been predominantly males. Scientists have speculated that the newcomers may have even been the originators of the caste system, assuring that their descendants would always be born into the higher ranks while at the same time the native or conquered individuals would remain in the lower castes. Scientists view the Hindu caste system, which is practiced by about one sixth of the people on earth, as an invaluable resource in the study and analysis of the effects of social conventions on human evolution.
The 18 Daughters of Eve
Dr. Douglas C. Wallace of Emory University School of Medicine in Atlanta has constructed a family tree for all the women in the world today based on mitochondrial DNA evidence. The tree has Eve at its base, and 18 branches stemming from her; these are her 18 "daughters" who spread out from Eve’s origin and populated the different regions of the globe, giving rise to the extant modern populations of humans throughout the world. This split in Eve’s progeny is believed by scientists to have occurred around 144,000 years ago, and this date appears to correspond to the period in which Y chromosome trees project that branching took place. Certain regions of the world are home to unique mutations within the mitochondrial DNA, and Wallace has named each of these haplotypes with a letter.
Nearly all Native American mtDNA fits into the four haplotype groups dubbed A, B, C, and D. European mtDNA appears to have descended from haplotypes H through K and T through X. Using the calculated time for the divergence of these European branches, Wallace gauges that the arrival of contemporary humans in Europe occurred between 39,000 and 51,000 years ago, a date supported by archaeological findings, which place the arrival at least 35,000 years ago. There is a single central Asian lineage identified as M, from which three descendant branches (E, F, and G) stem. Africa also has a principal lineage called L, which is further divided into three branches; the most recent of which (L3) is believed to be the origin of the European and Asian haplotypes. L3 is found most often in East Africa.
Dr. Wallace has also analyzed several modern populations in Africa in search of areas displaying mtDNA closest to that of Eve. The tests have identified the Vasikela Kung, who reside in the northwestern part of the Kalahari Desert of southern Africa, and the Biaka pygmies from Central Africa as populations having DNA most closely resembling the ancestral sequence. The relative isolation of these two groups of people could explain the apparent antiquity of their mitochondrial sequences.
In an effort to bring this technology out of the confines of science and into the world where it can be applied, Dr. Bryan Sykes of Oxford University in England has founded a company called Oxford Ancestors. Requiring simply a swab of cells taken from the inside of the cheek, the company is able to tell the customer from which of the seven European daughters of Eve they descend. The price of determining one’s ancestry is $180 per test, and when patrons are placed into their haplogroups, they are given an outline of the origin and life of that particular matriarch. While researching and organizing the seven European daughters, Dr. Sykes and the other Oxford Researchers discovered that all seven European daughters appear to be descendants of the Lara clan, one of the three extant lineages present in Africa today. This finding lends even more support to the theory of an African Eve. Dr. Sykes is currently working on a similar program for identification with the 14 African and 16 Eurasian and American lineages.
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Dr. Bryan
Sykes
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Dr. Sykes’ matriarchal lineages are consistent with Dr. Wallace’s haplotype letters, and he has named each of the daughters of Eve, on the assumption that they were in fact real women.
Helena- Helena’s clan originated in the frozen Pyrenees mountains about 20,000 years ago, and her progeny migrated to present day England as the climate of the region became warmer following the Ice Age. This migration is thought to have occurred somewhere around 12,000 years ago, and people belonging in this group are found throughout Europe today.
Jasmine- Her clansmen were originally Syrian farmers, who grew wheat and reared domesticated animals. As the clan spread throughout the rest of Europe, they carried with them their agricultural practices.
Katrine- The majority of modern Europeans belonging to this group reside in the Alps, but the lineage is thought to have originated around Venice about 10,000 years ago.
Tara- Tara’s group is believed to have branched out from Tuscany 17,000 years ago and dispersed to populate northern Europe, in time crossing the English Channel, populating Ireland.
Ursula- Ursula’s clan is characterized by their use of stone tools, and her descendants seem to have migrated across the whole of Europe and into France and Britain from their origin in Northern Greece. She is believed to have been born around 45,000 years ago.
Velda- 17,000 years ago Velda’s clan lived in northern Spain, with the later descendants moving primarily into northern Norway and Finland where some became the Saami or Lapps.
Xenia- 25,000 years ago this clan resided in the Caucasus mountains near the Black Sea and just after the end of the Ice Age Xenia’s progeny spread across Europe and apparently even into the Americas. (The X lineage is quite rare among Europeans but has been found in the Ojibwa and Sioux in the northern ranges of the Americas, evidence that some pre-Columbian migration must have occurred.)
Mungo Man
The skeleton of an anatomically modern human male was unearthed in New South Wales Australia in 1974, and DNA analysis was performed on it in 1999. Dating had originally placed the skeleton, called Lake Mungo 3, to be between 56,000 and 68,000 years old. These dates were found to be inaccurate however and the skeleton is now believed to be around 40,000 years old.
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What is surprising about this fossil, aside from its incredible age and apparent gracile characteristics, is that the mtDNA sequences isolated from the bones do not match those of the Australian Aborigines or any other known lineage in the modern world. One possible implication of this evidence is that this particular lineage may have evolved independently in Australia, casting doubt as to the certainty of the out of Africa migrations. Another possible explanation is that Mungo’s lineage actually originated in Africa and was carried to Australia via migration. The fact that this mitochondrial sequence has never been seen before suggests that the lineage went extinct in both Africa and Australia (and presumably everywhere else it may have been carried) following these migrations. This theory would also assume that LM3’s mitochondrial lineage branched off before the most recent common ancestor of mitochondrial lineages extant today. Scientists have discovered, however, that a portion of Mungo’s mtDNA sequence appears to have been inserted in the nuclear DNA of chromosome 11, a trait that is widespread among modern human populations.
Many scientists have also questioned the integrity of mtDNA analysis on a fossil of such great age, and organic molecules of comparable antiquity have only been recovered from fossils in very cold regions. Excavations in other regions of the world in climates similar to that of the Willandra Lakes area have shown that these conditions are not normally conducive to the preservation of DNA greater than 10,000 years old.
The First Americans
The Bering Land Bridge, which connected Siberia to what is now Alaska, is believed to have been the quirk of nature that allowed the population of the Americas by Paleolithic wanderers during the Ice Age. Studies done by a group of geneticists from Emory University in Atlanta have lent further evidence in favor of this theory, and have turned up surprising signs of multiple migrations to the New World.
The land bridge, which now lies under a mere 800 feet of water, rose from the sea as the Ice Age glaciers caused a significant decrease in the ocean levels as they consumed and froze the seawater. The exposed tundra or dry grassland would have supported large game, such as mammoths, bison and caribou, upon which the early humans presumably subsisted. It was in following these migratory animals that early hunters are believed to have crossed the bridge into the Americas. As the land bridge was swallowed up by the swelling seas at the end of the Ice Age, those humans that had crossed to the New World would have been trapped there, and probably spread to inhabit the rest of the continent.
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What Beringia would
have looked like during the Ice Age and Beringia today.
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Had such a migration actually occurred, the aboriginal Siberians inhabiting the area around the Bering Sea must have very similar mtDNA sequences to the Native Americans, or such was the reasoning of the Emory team. They culled samples from 10 populations of aboriginal Siberians and compared them to previously known Native American and Asian data. They found that the Siberian populations indeed displayed haplotypes present in the Native American mtDNA. Haplotypes A, B, C, and D are found in nearly all Native Americans, and the geneticists have located three of them (A, C, and D) in the Siberian natives. These findings point towards a founding population containing this small number of mitochondrial haplotypes, as would be expected had such a migration taken place, presumably between 17,000 and 34,000 years ago.
The team also discovered that there was no evidence of the B haplotype among Siberian populations, whereas it is present in the Americas. Surprisingly, they located this haplotype in East Asian populations, indicating that a separate migration to the Americas from this area was likely, probably between 13,000 and 16,000 years ago.
Other research has turned up further surprising data in support of multiregional colonization of the Americas. Haplogroup X is a rare mtDNA type found in certain Native American populations. So far, this haplogroup has only been identified in European and some Eurasian populations, and as yet has not been traced to any region of Asia. This evidence seems to indicate a separate migration by a small band of early Europeans (which included women), who may have come via water or migrated through Asia but left no descendants (and thus no X markers) behind them. Researchers estimate the timing of this migration to be around 12,000-36,000 years ago. This genetic evidence of a possible founding population of Caucasoid origin is very intriguing data for archaeologists and anthropologists investigating the relatively small pool of ancient American remains. These scientists have been puzzled by the unusual European features that characterize many of these early skeletons, and some have even isolated X in the ancient remains. Further research is being conducted in order to ensure that X is indeed absent in any Asian populations, but the evidence points strongly towards a much more diverse group of founders than previously thought.
Questions:
Some helpful websites for more in-depth research:
http://www.actionbioscience.org/evolution/ingman.html
www.nytimes.com/library/national/science/050200sci-genetics-evolution.html
http://www.nytimes.com/library/national/science/050200sci-genetics-evolution.2.GIF.html
http://www.nytimes.com/library/national/science/050200sci-genetics-evolution.1.GIF.html
www.geneticorigins.org/geneticorigins/mito/theory6.html
www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=7688933&dopt=Abstract
www.lds-mormon.com/morell_science_mtdna_american_europe.shtml
www.pbs.org/wgbh/nova/first/claimbonn.html
www.tucsoncitizen.com/history_culture/10_11_02origins.html
Pictures Cited (Top to bottom):
1. http://micro.magnet.fsu.edu/cells/animals/mitochondria.html
2. http://www.mdausa.org/publications/Quest/q95research.cfm
3. http://www.cytochemistry.net/Cell-biology/mitoch2.htm
4. http://www.usc.edu/dept/mda/180evolution/IMAGES/wmho.html
5. http://www.usc.edu/dept/mda/180evolution/IMAGES/wmho.html
6. http://www.beyondbooks.com/wcu91/6g.asp
7. http://www.gentech.org/ngsgentech/conferences/2002/brochure/banquet.asp
8. http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2001/01/09/wmung09.xml
9. http://www.lib.utexas.edu/maps/national_parks.html
References:
Duerinck, Kevin. "Genetics and Human Migration Patterns." 22 March 2003. http://www.duerinck.com/migrate.html
Duerinck, Kevin. "GENETICS AND GENEALOGY: Y Polymorphism and mtDNA Analyses." 19 Sept. 2002. http://www.duerinck.com/genetic.html
Wade, Nicholas. "The Human Family Tree: 10 Adams and 18 Eves." The New York Times on the Web. 2 May 2000. http://www.nytimes.com/library/national/science/050200sci-genetics-evolution.html
"Mitochondrial ‘Eve’ Theory." Freeman Institute. http://www.freemaninstitute.com/RTGdna.htm
Melton, Terry. "About Mitochondrial DNA." Mitotyping Technologies, LLC. 2002. http://www.mitotyping.com/dna.htm
"Fossil Challenge to Africa Theory." BBC News. 9 Jan 2001. http://news.bbc.co.uk/1/hi/sci/tech/1108413.stm
Torroni A, et al. "mtDNA Variation of Aboriginal Siberians Reveals Distinct Genetic Affinities with Native Americans." PubMed. from Am. Journal of Human Genetics. www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=7688933&dopt=Abstract
Morell, Virginia. "Genes may Link Ancient Eurasians, Native Americans." Ids-mormon.com. from Human Genetics. www.lds-mormon.com/morell_science_mtdna_american_europe.shtml
Brown, MC. "mtDNA Haplogroup X: An Ancient Link Between Europe/Western Asia and North America?" PubMed. from Am. Journal of Human Genetics. www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9837837&dopt=Abstract&holding=f1000
"Where we come from: recent advances in genetics are starting to illuminate the wanderings of early humans." US News.com. 34-41. 29 Jan 2001. http://www.justpacific.com/bits’n’pieces/genetics.html
"Phylogenetic Data from DNA Sequences." Campbell Biology, Sixth Edition. http://occawlonline.pearsoned.com/bookbind/pubbooks/campbell6e_awl/medialib/assets/e-books.htm
"Maternal Inheritance of Mitochondrial DNA." Dolan DNA Learning Center. http://www.geneticorigins.org/geneticorigins/mito/theory5.html
"Mitochondria and Plastids Evolved from Endosymbiotic Bacteria." Campbell Biology, Sixth Edition. http://occawlonline.pearsoned.com/bookbind/pubbooks/campbell6e_awl.medialib/assets/e-books.htm
"Lake Mungo 3." http://www-personal.une.edu.au/~pbrown3/LM3.html
Starikovskaya, Y.B. et al. "mtDNA Diversity in Chukchi and Siberian Eskimos: Implications for the Genetic History of Ancient Beringia and the Peopling of the New World." Am. Journal of Human Genetics, 63: 1473-1491, 1998. http://www.journals.uchicago.edu/AJHG/journal/issues/v63n5/970316/970316.text.html
Rozell, Ned. "A New View of the Bering Land Bridge Article #1304." Alaska Science Forum. 26 Sept 1996. http://www.gi.alaska.edu/ScienceForum/ASF13/1304.html
Bonnichsen, Dr. Robson. "Mystery of the First Americans." NOVA Online. Nov 2000. http://pbs.org/wgbh/nova/first/claimbonn.html
"The Molecular Clock and Anthropology." DNA Learning Center. 2000. http://www.geneticorigins.org/geneticorigins/mito/theory6.html
