Early humans must have wondered why a girl or a boy was equally likely at birth. Why did they appear in a 50:50 ratio and not, say, 67:33?
We know today that the answer has two parts.
How is sex decided at conception?
One part is that girls have two X chromosomes, one received from the mother and the other from the father, while boys have an X from the mother and a Y from the father. The SRY gene on the Y chromosome triggers development along the male pathway. If this pathway is not triggered, development proceeds along the default pathway, towards femaleness.
The other part of the answer is that 50% of a father’s sperm carry the X chromosome and the other 50% carry the Y – not 67% and 33%, or some other ratio. This is the result of a special form of cell division called meiosis, which is how the body makes sperm. Meiosis is like tossing a coin. If the coin flips heads, the sperm receives the X chromosome; if it flips tails, it receives the Y.
X- and Y-bearing sperm are equally able to fuse with an egg. So girls and boys are equally likely.
Meiosis also occurs in the woman when her body makes eggs. If the coin flips heads, the egg receives the maternal X chromosome, and if it flips tails, it receives her paternal X chromosome.
The transmission of chromosomes, and the genes they contain, in this way from parent to child is called Mendelian transmission.
What are the implications of Mendelian transmission?
In 1865, the Austrian biologist Gregor Mendel established that heads and tails were equally likely for all the 23 pairs of human chromosomes, not just the sex chromosomes. Other geneticists subsequently showed that it applied to all plants and animals as well.
An early human might have been as impressed as I was reading a 1989 article written by a geneticist named Terrence W. Lyttle, who worked with fruit flies (Drosophila melanogaster). Dr. Lyttle had ‘constructed’ male flies that produced sperm cells containing only the X chromosome, never the Y chromosome. He did this by engineering all Y-bearing sperm to fail to mature. As a result, the engineered male flies only fathered daughters.
Conclusion: Mendelian transmission had been violated.
Geneticists had previously discovered and studied sporadic instances in nature in which Mendelian transmission had been broken. One example comes from the so-called segregation distorter (SD) chromosome in fruit flies.
In male fruit flies that carry the SD chromosome, sperm that contained a gene called Rsps became inviable. Dr. Lyttle transferred the Rsps gene to the Y chromosome. Then, he made a male fly with the engineered Y and SD chromosomes. And voila: only sperm bearing the X chromosome matured. When the Rsps gene was transferred to the X chromosome, male flies bearing the engineered X and the SD chromosomes fathered only sons.
Examples of non-Mendelian transmission have also been found in mice. But deviations from Mendelian transmission have never been reported in humans – yet it wouldn’t be wise to believe humans are the exception. Deviations from Mendelian transmission are also exceptional, so their discovery has always been by accident.
Where else has non-Mendelian transmission been found?
In May 2022, researchers in the U.S. reported non-Mendelian transmission of a particular chromosome in a fungus called Fusarium verticillioides, a pathogen of maize that rots the part of the crop that bears the kernels. People who consume kernels from infected plants are exposed to a fungus-derived toxin, fumonisin, that increases their risk of cancer and neural-tube defects, and stunts growth.
F. verticillioides has a different life cycle than humans. Its initial cell is a spore called an ascospore. The ascospore germinates to produce cells called hyphae. Ascospores and hyphae have 11 chromosomes each – i.e. one copy of the F. verticillioides genome each.
Only a cell called the ascus contains two copies of the genome (22 chromosomes). An ascus is made when two hyphae, one from each parent, fuse. The ascus then undergoes meiosis to make eight ascospores.
The researchers mated one F. verticillioides strain containing a particular chromosome, which had a gene called SKC1, with a strain that didn’t contain this chromosome. Let’s call this strain ‘Sks’. The two had the usual eight progeny. Four inherited the chromosome; four didn’t – and died.
Ordinarily, ‘Sks’ strains are viable: if two ‘Sks’ strains mate, they produce eight viable progeny ascospores per ascus. But in this case, all the progeny that didn’t inherit the particular chromosome died. It was a deviation from Mendelian transmission.
How might non-Mendelian transmission arise?
In search of an answer, the researchers introduced the SKC1 gene into a different fungus, Neurospora crassa. Both F. verticillioides and N. crassa are fungi of the phylum Ascomycota. When they reproduce sexually, both take the ascus route.
When they mated an N. crassa strain containing the SKC1 gene with an N. crassa strain that didn’t, all the resulting eight ascospores died. Why did all ascospores die in N. crassa but only four in F. verticillioides?
One way this is possible is if the particular chromosome in F. verticillioides has an additional gene that protects ascospores against the chromosome’s killing effect. Because the particular chromosome in N. crassa wouldn’t have the same gene, its progeny would die. Other researchers will have to conduct more tests to validate this hypothesis. (If they do, we may have a way to keep F. verticillioides from infecting maize crops.)
In the meantime, however, the study gives us a good example of how non-Mendelian transmission – an exceptionally unusual mechanism in nature – can arise as the result of a simple change in the reproductive process of an obscure fungus. And, to borrow the words of the English biologist William Bateson, who coined the word ‘genetics’, geneticists learn to treasure their exceptions.
D.P. Kasbekar is a retired scientist.
- The transmission of chromosomes, and the genes they contain, on how the female’s eggs receive the male’s X or Y chromosome from parent to child is called Mendelian transmission.
- Geneticists had previously discovered and studied sporadic instances in nature in which Mendelian transmission had been broken. One example comes from the so-called segregation distorter (SD) chromosome in fruit flies.
- Examples of non-Mendelian transmission have also been found in mice. But deviations from Mendelian transmission have never been reported in humans – yet it wouldn’t be wise to believe humans are the exception. Deviations from Mendelian transmission are also exceptional, so their discovery has always been by accident.