The chance mutations that are fixed in the DNA of our mitochondria and accumulate there have been used to trace the spread of human beings across the globe. Passed on in a matrilineal form, we all receive the mtDNA from our mother's ovum. Our father's sperm does not carry any mitochondria. Randmo mutations gradually accumulate so they serve as markers in the mtDNA and specific markers define haplogroups.
A paper suggests that these random mutations are then shaped by the forces of Natural Selection. (D. Mishmar, E. Ruiz-Pesini, P. Golik, V. Macaulay, A.G. Clark, S. Hosseini,M. Brandon, K. Easley, E. Chen, M.D. Brown, R.I. Sukernik, A. Olckers, & D.C. Wallace, /2003) Natural selection shaped regional mtDNA variation in humans, Proc. Natl. Acad. Sci. U.S.A. 100 (1) 171-176, https://doi.org/10.1073/pnas.0136972100).
They note that although mutations arise in a random way in the mtDNA, as they have an effect on the mitochondria which produce the body's cells energy and regulate cellular metabolism by producing the energy-rich molecule adenosine triphosphate (ATP), they may be a target of natural selection. They state that "Natural selection shaped regional mtDNA variation in humans."
Molecular clock affected
The fact that mutations are not neutral, and are acted upon by natural selection, implies that the assumptions on which the mtDNA molecular clock are based, are flawed. The paper warns: "If selection has played an important role in the radiation of human mtDNA lineages, then the rate of mtDNA molecular clock may not have been constant throughout human history. If this is the case, then conjectures about the timing of human migrations may need to be reassessed."
The molecular clock based on mtDNA is based on an axiom: genes accumulate new mutations in a clock-like manner, so knowing the rate at which mutations take place (i.e. 3 mutations per 10,000 years), and measuring the average amount of mutations that have appeared since a particular node on a phylogenetic tree (9 mutations), allows us to date the node: 30,000 years. And from there date other nodes based on the number of mutations and the mutation rate.
This is reasonable as long as the mutation rate is constant. But if it varies, then it will provide incorrect dates.
Positive selection could affect the mutation pattern similar and cause an acceleration in the mutation speed. (Further reading on the mtDNA clock: Eva-Liis Loogväi, Toomas Kivisild, Tõnu Margus, Richard Villems (2009))
mtDNA and Selection
After a long stasis in Africa where the L haplogroup is found, humans moved into Eurasia and two branches, or clades, M and N formed outside of Africa and comprise all the mtDNA diversity in the rest of the world. M and N are derived from the African haplogroup L3. And the split is supposed to have taken place around 55-70 kya, during the Out of Africa Event.
Interestingly, M is basically absent in the Middle East, yet it is found in Ethiopia, Southern Arabia and in India and East Asia, suggesting to some a Southern route of migration out of the Horn of Africa across Bab el Mandeb and Hormuz straits. However, a paper published in 2018 by Vicente M Cabrera, Patricia Marrero, Khaled K Abu-Amero, and Jose M Larruga, suggests that both M and N originated in Southeast Asia and migrated westwards. In the case of N haplogroup, it was believed to have formed in the area that links the Levant and Africa and that it appeared in humans taking a northern route out of Africa into Eurasia. But this paper suggests that N originated in Southeast Asia, and moved west across Asia towards Africa. The authors argue that "If one accepts that basal L3 lineages (M, N) evolved independently in southeastern Asia and not in Africa or near the borders of the African continent where the remaining L3 lineages expanded, one is confronted with the question of where the basal trunk of L3 evolved. A gravitating midpoint between eastern Africa and southeastern Asia would situate the origin of L3 in inner Asia."
The paper then states:
"L3 exited from Africa as a pre-L3 lineage that evolved as basal L3 in inner Asia. From there, it expanded, returning to Africa as well as expanding to southeastern Asia, giving rise to the African L3 branches in eastern Africa and the M and N L3 Eurasian branches in southeastern Asia, respectively. This model, which implies an earlier exit of modern humans out of Africa, has been tested against independent results from other disciplines...."
The paper includes the following maps as its Figure 1, and the caption reads: "Geographic origin and dispersion of mtDNA L haplogroups: a Sequential expansion of L haplogroups inside Africa and exit of the L3 precursor to Eurasia. b Return to Africa and expansion to Asia of basal L3 lineages with subsequent differentiation in both continents. The geographic ranges of Neanderthals, Denisovans and Erectus are estimates only."
The paper adds that the "early return and subsequent expansion inside Africa of carriers of L3... haplogroup might help explain, the Neanderthal introgression detected in the western African Yoruba and in northern African Tunisian Berbers." (see my recent post on Neanderthals in Africa).
The authors assume anatomically modern humans left Africa in an early migration 125 kya , met with Neanderthals in south-central Asia, admixed and as the climate worsened ~75kya, the humans moved west and returned to Africa (with the L3 variant with them and it diversified there), and they also moved east reaching SE Asia and China.
Selection and Diversification
Getting back to Mishmar et al., they argue that in Eurasia the M and N lineages spread across the continent in different lineages: A, C, D, and G. Which have a "striking regional variation, traditionally attributed to genetic drift. However, it is not easy to account for the fact that [these lineages] show a 5-fold enrichment from central Asia to Siberia". They argue that this enrichment is the result of natural selection acting as people left their traditional environment (warm, tropical, or temperate climates) and advanced into harsher and colder continental climates in Central and Northern Asia.
The researchers analyzed 104 complete mtDNA sequences from across the world and found that the African haplogroups more or less followed the neutral model, but American, European, Siberian and Asians didn't, they deviated from it. They found that the ATP6 gene, which is a "conserved" mtDNA protein had the highest variation in its amino acid sequences. "Conserved" means that it has remained mostly unchanged over the ages and among individuals and species because it has a low tolerance for mutations, because it is critical for cellular function. So, why would it present so many mutations?
To find out why, they compared the ratios of mutations for the ATP6 gene in different climate zones (arctic, tropical, and temperate) and found that it was highly variable in mtDNAs from the Arctic. Another mtDNA protein called cytochrome b which helps move electrons and create a proton gradient, essential for cellular energy production, was particularly variable in the temperate zones. Another protein, cytochrome oxidase I (or COX1), which also plays a vital role in electron transport, was more variable in the tropical areas. The authors concluded that "selection may have played a role in shaping human regional mtDNA variation and that one of the selective influences was climate."
They then downplay the effects of founder effects arguing as follows:
"..there are striking differences in the nature of the mtDNAs found in different geographic regions. Previously, these marked differences in mtDNA haplogroup distribution were attributed to founder effects, specifically the colonizing of new geographic regions by only a few immigrants that contributed a limited number of mtDNAs.
However, this model is difficult to reconcile with the fact that northeastern Africa harbors all of the African-specific mtDNA lineages as well as the progenitors of the Eurasia radiation, yet only two mtDNA lineages (macrohaplogroups M and N) left northeastern Africa to colonize all of Eurasia and also that there is a striking discontinuity in the frequency of haplogroups A, C, D, and G between central Asia and Siberia, regions that are contiguous over thousands of kilometers.
Rather than Eurasia and Siberia being colonized by a limited number of founders, it seems more likely that environmental factors enriched for certain mtDNA lineages as humans moved to the more northern latitudes.
Natural selection has been hypothesized to explain anomalies in the branch lengths of certain European and African mtDNA lineages."
However, a paper by Taku Amu and Martin Brand (2007), disagrees with this concept, and states that there were no differences between the mitochondrial energy management in Arctic or Tropical populations, and that the mutations which were expected to lower coupling efficiency leading to more heat generation in colder climates wasn't detected, and in fact, "Contrary to the predictions of this hypothesis, mitochondria from Arctic haplogroups had similar or even greater coupling efficiency than mitochondria from tropical haplogroups."
More recent research by Jukka Kiiskilä et al (2021) also notes that mtDNA variants are under natural selection and that different mtDNA haplogroups exert a different effect on the physical performance in athletes! the paper looked at Finnish military conscripts and reported that "Following a standard-dose training period, excellence in endurance performance was less frequent among subjects with haplogroups J or K than among subjects with non-JK haplogroups."
Takayuki Nishimura and Shigeki Watanuki (2014) studied mtDNA haplogroup D vs. non-D groups regarding body warmth, and found that "[Non shivering thermogenesis] NST was greater in winter, and that the D group exhibited greater NST than the non-D group during winter...no significant differences in rectal and skin temperatures were found between groups in either season. Therefore, it was supposed that mitochondrial DNA haplogroups had a greater effect on variation in energy expenditure involving NST than they had on insulative responses... individuals from the D group exhibited greater winter values of ΔVO2 than individuals from the non-D group." So, mtDNA haplogroup D subjects had higher oxygen uptake (ΔVO2), meaning their body was "burning" more oxygen but not shivering or increasing the temperature. This suggests an efficient use of energy to heat the core only, and it has a clear mtDNA haplogroup component to it.
Interestingly, Haplogroup D seems to enhance energy burn (without shivering), and without increasing external temperature. From an engineering point of view this is great, since the ΔT or temperature differential between a body and its surroundings impacts directly on the energy loss (Q) the body experiences: Q = U · A · ΔT (where "A" is the area that transfers heat loss, and "U" is a heat transfer coefficient). So this is why the study didn't notice differences in skin or rectal temperatures.
Closing Comments
If random mtDNA mutations somehow provide an adaptative advantage (efficient energy use to keep warm in cold climates), and natural selection acts upon it, then the "neutral" theory is mistaken, and the molecular clock used to calculate dates is also wrong.
Patagonian Monsters - Cryptozoology, Myths & legends in Patagonia Copyright 2009-2026 by Austin Whittall ©
No comments:
Post a Comment