What explains mtDNA introgression among archaic human populations?

3 minute read

In case anyone still wonders how variation in mitochondria might have been important to Neandertals and other archaic humans:

A bizarre find: Tiny powerhouses in your cells run at 122 degrees
The researchers grew human kidney cells and skin cells in petri dishes, which they kept at 38 degrees Celsius. Into these cells the scientists inserted a new type of fluorescent dye, which brightens as it cools. When the mitochondria became active, the fluorescence dimmed. This indicated that the temperature within the mitochondria rose between seven and 12 degrees Celsius, or an average of 10 degrees, as reported in the journal PLOS Biology on Thursday.

Previous researchers have suspected that human variation in mtDNA might relate to the tradeoff of heat production and ATP efficiency in mitochondria, with advantages for some mtDNA haplogroups in cold-adapted human populations. Circumstantial evidence for this hypothesis has been known for more than a decade, and I wrote about it back in 2005: “Mitochondrial DNA adaptations in living human populations”.

Even if important differences in mitochondrial function exist between human populations, mitochondrial DNA may not be the cause. Most of the genes that influence mitochondrial function are encoded in the nuclear genome, not the mtDNA. Yet some of the genes on the mtDNA do influence mtDNA function in ways that may have been selected in humans. Also, the mtDNA is the only part of the eukaryotic genetic complement that must function inside the mitochondrion itself, exposing it to a distinctive intracellular environment with its own possible effects on transcription.

The story of mtDNA in archaic humans has become more and more intricate. The earliest-known members of the Neandertal lineage, from Sima de los Huesos, Spain, have an ancient haplogroup that has not been found in later Neandertals or modern humans. This clade has been identified in Denisovans, although the variants in the Denisovan individuals known so far are fairly distant from the chronologically earlier Sima de los Huesos individuals.

Meanwhile, later Neandertals share a mtDNA clade that connects them more closely to the common mtDNA ancestor of modern humans, including all living African and non-African people. The origin of this clade is not known. It may have originated in Africa and have been exchanged into Neandertals by introgression some 250,000 years ago or more. Alternatively, it may have originated elsewhere and introgressed into both African and Neandertal populations. The extensive introgression of this mtDNA variant, in the absence of strong evidence of nuclear genome introgression at the same time, suggests that natural selection may have driven the mtDNA introgression.

No living people have been found with a mtDNA haplotype within the variation found within either the Neandertals or the Denisovans. Instead, everyone living today belongs to a subclade that originated within the last 300,000 years.

It is not currently clear whether this mitochondrial Eve lived before the populations that gave rise to all modern humans began to differentiate from each other. That differentiation began before 300,000 years ago, according to recent studies of African genetic variation from the nuclear genome. That’s earlier than most estimates of the date of the common mtDNA ancestor.

Within Africans today is much more mtDNA clade diversity than outside Africa. Throughout the pre-Columbian populations of most of the world, all people have mtDNA sequences that belong to two narrow branches of the mtDNA tree, which seem to have originated in the last 100,000 years. It is within these low-variation branches that a few functional variants have been found that might differentiate cold-climate populations from others. The adaptive story that has been examined so far for mtDNA does not relate to the much greater mtDNA variation that still exists within sub-Saharan African peoples.

I’ve been interested in mtDNA selection for a long time, and wrote about it in a 2006 paper: “Selection on mitochondrial DNA and the Neanderthal problem”.

There is a lot left to learn, which will no doubt leave today’s knowledge looking pretty inadequate. But what seems like mtDNA total replacement within Neandertals was a pretty striking event, and deserves more consideration as a possible case of adaptive evolution.