The first genetic rule states that gametes unite at random, however tests
suggest that occasionally eggs actively choose sperm for their genetic
advantages.
Millions of sperm compete in a winner-take-all sprint toward the egg that
is waiting at the finish line during fertilization. Due to missing or
malformed tails and other flaws, many sperm never even reach the starting
line. Others
run out of energy
before finishing the exhausting voyage through the female reproductive
canal, or they become entangled in gummy fluid that is designed to snag all
but the fastest swimmers. The ultimate victor would be selected by one last
race to the finish line for the subset of a subset of spermatozoa that reach
their trophy. The egg waited quietly till the Michael Phelps of gametes
eventually came; the sperm's precise identification was random. Or so
researchers believed.
This conventional wisdom is being contested by Joe Nadeau, chief scientist
of the Pacific Northwest Research Institute. In theory, random fertilization
should result in kids with precise gene ratios, however Nadeau has
discovered two instances from only his own lab that show fertilization can
be anything but random: It is substantially more likely for some gamete gene
pairs than for others. He had to come to the obvious conclusion that
fertilization wasn't at all random after ruling out all other
possibilities.
Nadeau described it as "the gamete equivalent of picking a mate."
His idea that the egg could seduce sperm with certain genes and that sperm
could do the same for the egg is part of a growing biological understanding
that the egg is not the passive, servile cell that scientists have long
believed it to be. Instead, scientists now consider the egg to be a
comparable and active participant in reproduction, adding levels of
evolutionary control and selection to one of the most critical life
processes.
According to Mollie Manier, an evolutionary biologist at George Washington
University, "Female reproductive anatomy is more obscure and difficult to
investigate, yet there is an increasing acknowledgment of the female
involvement in conception."
Cellular-level sexual selection
The concept of sexual selection predates Charles Darwin by several hundred
years. He cited the flashy tail of the peacock and the enormous antlers of
the elk as examples of features that developed to assist men advertise their
attractiveness as mates to females in On the Origin of Species. For the
following century, biologists concentrated on every facet of sexual
selection that took place in the circumstances preceding copulation. After
mating, the female had already made her decision, and the sperm swimming
toward the egg constituted the sole rivalry.
According to
Emily Martin, an anthropologist at New York University, this male-oriented perception
of female reproductive biology as mainly compliant was widespread. Martin
made this claim
in a 1991 study. The egg is perceived as being big and unactive. It 'transports' itself
passively along the fallopian tube rather than moving or traveling. Sperm,
on the other hand, are tiny, "streamlined," and always active, she
said.
But starting in the 1970s, science started to disprove that myth. The
Smithsonian Tropical Research Institute's behavioral ecologist
William Eberhard
has studied all the ways in which females may influence which males
fertilize their eggs even after mating. It's a large list, and researchers
are still unsure if they have covered everything. These discoveries weren't
all made too late because of sexism. Games of hide-and-seek with sperm
within the female reproductive canal are considerably harder to notice than
two walruses sparring with their tusks.
"Sexual selection begins as soon as you have eggs and sperm. Eggs and
seminal fluid are capable of amazing things, according to evolutionary
scientist
Andrea Pilastro
of the University of Padova in Italy.
Females of animals whose fertilization takes place externally frequently
cover their eggs in a viscous, protein-rich fluid called ovarian fluid. The
University of East Anglia in England's
Matthew Gage
conducted experiments in 2013 that demonstrated this fluid carries chemical
cues to aid in attracting the right kind of sperm. When salmon and trout
eggs were
exposed
to combinations of sperm from both species, the eggs' own species fertilized
70% of the time, which is substantially more often than would be predicted
by chance.
"The sperm exhibited distinct behaviors in various ovarian secretions. In
their own fluid, they actually swam more straight, according to Gage.
The techniques used by internal fertilizers are what Eberhard called
"cryptic female choice." Some female reproductive tubes are labyrinthine,
with dead ends and false beginnings that
can obstruct sperm
except for the strongest. Biologists believe that a large majority of
animals, including many species of reptiles, fish, birds, and amphibians,
copulate with more than one male. Some females may store sperm for months or
even years by changing the storage environment, which stacks the odds in
favor of one male. Many female birds, including domestic chickens, have the
ability to
expel sperm after mating, allowing them to select the best male during fertilization.
However, all of these methods merely provide females the chance to choose
from a variety of male sperm. Which sperm fertilized the egg inside an
ejaculate still appeared to be up to chance.
In fact, the first law of genetics, which dates back to Gregor Mendel, the
principle of segregation, contains an implicit statement about the
randomness of fertilization. Each gene has two copies in each parent, and
these copies are randomly distributed into gametes, each of which has only
one copy. It is what gives birth to many of the probability that high school
biology students learn. Half of the kids would also be heterozygotes if both
parents are heterozygotes, which means they both carry two different copies
of the same gene. One version would be present in two copies in one-fifth of
the kids, while the other one-fifth would be homozygotes bearing the other
version.
It's one of biology's most universally applicable laws, according to
Nadeau.
But only if fertilization is random do these probability make sense. Those
ratios may be considerably different if the sperm or the egg has any ability
to change the other gamete involved in conception. Nadeau was first drawn to
this obvious distinction in 2005. The probability were all wrong when he
started examining how two specific genes in mice are inherited. He started
to ponder at his lab in Seattle: Could Mendel have been wrong?
Nadeau hadn't intended to query Mendel about the Mendelian Lawbreakers. As
testicular cancer is one of the most heritable types of cancer, he was more
interested in how interactions between two genes (Apobec1 and Dnd1) altered
risk factors for the disease. Everything
seemed to obey
Mendel's laws when Nadeau and his doctorate student Jennifer Zechel crossed
female mice bearing one normal and one mutant copy of Dnd1 with heterozygote
Apobec1 males. Good news thus far, They discovered that only 27% of the
anticipated progeny possessed copies of mutant Apobec1, mutant Dnd1, or
both, in contrast to the 75% they had anticipated to observe when they
reversed the breeding (a female Apobec1 heterozygote mated with a male Dnd1
heterozygote).
Nadeau was aware of a wide range of variables that may impact Mendel's
ratios as a scholar who had spent many years researching heredity. The
resultant embryo might not survive development if a fertilized egg ended up
with two mutant copies of a recessive gene. The ratio of homozygotes to
heterozygotes would change as a result of such embryonic-lethal mutations,
but the average number of mouse pups in each litter would also decrease.
However, Zechel and Nadeau discovered no indication of early embryonic death
in any of their mice, all of which had typical litter sizes.
Nadeau reasoned that perhaps the issue was with the sperm rather than the
egg. In order to test if the mutation affected sperm development, he bred
male mice with and without the mutation to healthy, mutant-free females, but
discovered no changes in the males' fertility. If the mutation had an impact
on sperm creation, this would have been clear. Nadeau and his team gradually
ruled out all potential causes of these odd ratios of child genotypes, with
the exception of one: that the egg and sperm were genetically biased towards
the mutant genotype during fertilization.
Nadeau reasoned that someone else must have already noticed this, so he
looked through the scholarly literature. He could identify several instances
of unusual offspring ratios, but no one had really looked at genetically
biased fertilization as a potential solution.
Everyone basically assumed it to be embryonic lethality, according to
Nadeau, since we see what we look for and explain things using our
knowledge.
One of the cases Nadeau discovered came from the University of Alberta lab
of cancer researcher
Roseline Godbout. Godbout investigated how the retinoblastoma, a highly heritable pediatric
disease, is influenced by a protein called DDX1. Mice having one functioning
copy of the DDX1 gene removed (but with a second, completely functional gene
as a backup) seemed healthy and normal. Even though straightforward
Mendelian math would indicate that 25% of the progeny should lack
both copies
of DDX1, Godbout and Devon Germain, a postdoctoral fellow at the Max F.
Perutz Laboratories in Vienna, found that none of the kids lacked both
copies of the gene. The fact that the gene is crucial for DNA replication,
however, meant that this wasn't shocking: The homozygotes lacking DDX1 most
likely perished soon after conception. Additionally, Godbout and Germain
discovered fewer homozygote children with two copies of DDX1 than they
anticipated. The scientists proposed that their findings were the
consequence of a rare mutation that had happened in the DDX1 gene during
their tests after a complex series of mating trials.
Nadeau was not persuaded. He asked Godbout in a letter how her lab had
shown that the "knockout" homozygotes without the DDX1 gene had perished
during embryonic development. Not at all. Additionally, he enquired as to
whether they had thought of genetically biased fertilization, in which the
egg would prefer to mate with a sperm carrying the opposing DDX1
genotype.
Germain remembered, "We genuinely assumed it was just an odd pattern of
heredity." We had not given nonrandom fertilization any attention.
Later, on a whim, Germain made the choice to examine all of the
experiment's raw data. He thought back to Godbout's inquiries that had been
sparked by Nadeau's email as he reviewed the findings. The more he examined
the data, the more "the most reasonable explanation"—genetically biased
fertilization—appeared, he claimed.
In "Can Gametes Woo?," an essay that was published in
October in Genetics, Nadeau outlined his theory after becoming frustrated at how little
research had been done on genetically biased fertilization as a possible
explanation for their findings. He stated that his intention was to
encourage more study in this field and ascertain whether and how
interactions between sperm and egg might affect conception.
"Our preconceived notions have rendered us blind. It has extremely distinct
ramifications for the fertilization process and requires a different way of
thinking about fertilization, according to Nadeau.
Nadeau's concept is fascinating and even conceivable, according to other
scientists like Manier of George Washington University, but they draw
attention to the fact that no one has provided any supporting data. Nadeau
concurs and suggests two scenarios.
The first involves the metabolism of B vitamins, including folic acid,
which helps sperm and eggs produce key signaling molecules. These chemicals
have a significant impact on fertilization, according to
Nadeau's research, and he thinks defects in certain signaling genes may affect how much the
sperm and egg are attracted to one another.
A rival theory is based on the observation that sperm are frequently
present in the female reproductive tract prior to the last round of cell
divisions that results in the egg. These cell divisions may be influenced by
signals from the sperm, which may also bias the identity of the cell that
develops into the egg.
This work challenges the widespread belief that female physiology is
passive during fertilization, whatever the mechanism may be. Females were
previously thought of as passive, helpless objects, but now, according to
evolutionary scientist Renee Firman of the University of Western Australia,
they will have a stake in the success of conception. Although there is still
much to learn about this process, I don't believe we really get how often
and commonplace it is.
It could be difficult to find evidence to prove or disprove this idea,
according to Manier. It will be necessary to demonstrate that the sperm's
surface chemicals are affected by genes, and that the egg can detect these
variations. Such outcomes need for in-depth biochemical analyses of
individual sperm cells and genome sequencing data.
When Nadeau delivers the findings of his mouse research and his theory for
what is happening, he is ready for naysayers since he has faced many of them
at conferences. After the discussion, critics frequently come up to him and
start asking him questions. Uncertain of whether they leave persuaded,
Nadeau believes they are less sure that biased fertilization doesn't occur.
The circumstance is the perfect Sherlock Holmes scenario, according to
Harmit Malik, a geneticist and virologist at the Fred Hutchinson Cancer
Research Center.
He joked, "If you've ruled out the impossible, then what's left, however
doubtful, must be the truth."
This article was reprinted on
TheAtlantic.com.
