Why the dogma of strict maternal inheritance of mtDNA should be corrected

The current prevailing view in biological science is that the DNA of mitochondria, the structures that convert nutrients into cellular energy, is passed on only through maternal inheritance. How this idea came to be, and a theory on why it's wrong, is the subject of a review paper by physical anthropologist Jeffrey H. Schwartz. 

Writing in the May journal Mitochondrial DNA, Schwartz carefully documents the history of our understanding of mitochondria and how maternal mitochondrial DNA (mtDNA) inheritance evolved into a dogma. As he demonstrates, the idea of strict maternal mitochondrial inheritance has persisted in evolutionary biology, even though the science on which it is based is "now generally accepted as false."

Two assumptions underlie the mtDNA maternal-only inheritance concept: First, that mitochondrial replication occurs only via cloning; and second, that of homoplasmy, the idea that all the mitochondria in an organism’s cells have the same mtDNA sequence. Any differences in individual or species sequences are assumed to be caused by mutation only, not by the combination of maternal and paternal mtDNA.

The unnatural history of mtDNA is based on the now-disproven assumption that only the head of the male sperm penetrates the female's egg, which was generalized from the rare cases – such as in ragworms – where this is true.

Schwartz references the scientific research of the 1800s and 1900s, reviewing the experimental work and quoting in detail from specific research papers on fertilization. He explains the genesis of the idea that only the head of the sperm penetrates the egg, while the midsection, which contains the paternal mitochondria, and the tail, remain outside. 

This head-only concept became dominant, Schwartz suggests, in part because it was reiterated by one of the most widely used biology texts until the 1960s: H.G. Wells' "The Science of Life." 

Yet, when realized that the entire sperm typically enters the egg, the notion of maternal inheritance persisted and still dictates how mtDNA is interpreted by molecular anthropologists, even in the face of ever-increasing evidence of paternal mtDNA transmission.

What about paternal mtDNA?

Current Science Daily interviewed Jeffrey Schwartz, professor emeritus in the Department of Anthropology at the University of Pittsburgh, about the evidence for the transmission of paternal mtDNA.

"The overwhelming evidence of paternal mtDNA transmission comes from studies of all the major groups of animals, insects, birds, fish and mammals, including humans, as you can see in the tables in my article," he said.

One of the best cases for transmission of paternal mtDNA, he said, concerns a son whose mitochondrial disease was passed on by his father, not his mother. 

"There really is no evidence to support the notion of the universal inheritance of only maternal mtDNA. It's been assumed for so long and repeated so many times," that it has simply become accepted as truth. It is true in a few unique cases — he cited a tunicate marine animal and the worm C. elegans — but the rest is "fiction," Schwartz said.

Schwartz noted that to find evidence of paternal mtDNA, "you have to have the desire to look for it. The technology now exists, but you have to want to do it. If you believe that mtDNA is only inherited through the mother, you're not going to do it."

When DNA was discovered, he said, "it was assumed that since paternal mitochondria don't get into the egg, their DNA doesn't. So, fathers wouldn’t contribute their mtDNA to offspring." It's an "odd situation, where a particular story replaces biological reality."

As the journal article concludes, "no matter how sophisticated the technology, the results and their interpretation are no better or more ‘correct’ than their underlying assumptions.”

A phylogenetics problem

"The dogma is in the area of phylogenetics, in systematics. It's not in the fields of molecular biology and molecular medicine," Schwartz said.

"All of the possibilities have to be considered in medicine because mtDNA-related disease is a serious problem and you have to monitor everything that's going on in all mitochondria, because each mitochondrion houses hundreds of mtDNA with different sequence lengths and sequence composition," he said. "So, it's very important in the medical/clinical realm to be cognizant of all biological possibilities."

In respect to evolutionary biology, Schwartz commented that "it makes it really easy to do systematics and phylogenetic reconstruction if mtDNA is only maternally inherited, replicates by cloning, and changes only by mutating. But it's not biologically real."

The problem of a molecular approach

He stressed that the belief of universal maternal mtDNA inheritance has phenomenal consequences. 

Schwartz cited, for example, the molecular evidence that Neanderthals and humans interbred. 

"If you consider the entire human fossil record, DNA sequences have only been retrieved from some Cro-Magnon-like Upper Paleolithic specimens, from a handful of Neanderthals, from two specimens from a site in Spain, and a few so-called Denisovan teeth and one finger bone. That represents less than 0.5 percent of the human fossil record, which is a very myopic view of human evolution," he said.

"But if you actually study the fossils, it’s obvious that humans and Neanderthals differ from one another in almost every part of their skeleton-- bones, teeth, arms, joints, everything," Schwartz said. "The question is, then, would either of them recognize the other as a potential mate? The answer would likely be no. They are just so different. I know, because I’ve studied virtually the entire human fossil record, and published four volumes and numerous articles on the fossils.”

Further, he noted, animals that do hybridize look pretty much like one another.

"One of the consequences of jumping on the molecular anthropology bandwagon, and relying only on molecules, is that you're not considering the entire biology of an organism. The animal itself isn't there. All people are talking about is their DNA," he said.

How to change the consensus

Schwartz made a few recommendations about changing the situation. First, he suggested that "molecular geneticists and phylogeneticists should start reading the molecular biological literature, which they don't apparently do.... They certainly don’t cite it in their articles. If they did read it, they would know that maternal transmission is not universal."

Schwartz said that since the 1970s, "human paleontologists and others have swallowed whatever the molecular anthropologists tell them. The molecular folks have been elevated to an almost godlike status, and the religion of DNA goes beyond the realm of what DNA actually is and what it can explain."

He also suggested that the public must be more informed on the subject. 

"It's a hard nut to crack. As long as the molecular folks make these claims and the media reiterate them, they'll keep doing the same thing," he said. "If the public were better informed, and able to question their claims, the molecular folks would have to shape up."

A `historian of ideas'

Schwartz characterizes himself as an historian of ideas. He studied both biology and anthropology in college and graduate school and was interested in development, the origin of mammals, and the relationship of humans and primates. 

"I wanted to know where the ideas about evolutionary relationships came from," he said. "So, I also started to immerse myself in publications on molecular systematics. That's my background. I've always been interested in how you think about species and how you think about their relationships.

"You have to think about morphology, and fossils, and the molecules. I think people have to have a more holistic and collaborative approach to phylogenetics and systematics."

Schwartz would like people to take away from his article the idea that "biology is complex, and there's elegance in its complexity."

"When scientists, especially evolutionary biologists, make definitive statements based on received wisdom, you have to question that, because, while evolution is real, you cannot demonstrate the entire history of what happened," Schwartz said. " You can hypothesize what happened and falsify that hypothesis, but you can never really prove it."

There's also a psychological aspect to the situation, Schwartz said. 

"You learn something from your professors and then base your career on it. It's difficult to say 'I've just spent my whole career doing this and I've been wrong all this time.'"