Tall midwit
The eyes are at the end of the day everything
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Genetic Incompatibility
When Being Too Unrelated Can Also Cause Problems
When Being Too Unrelated Can Also Cause Problems
We're all familiar with the risks of incest/inbreeding. The closer a man and woman are genetically, the greater the chance that both carry the same harmful recessive allele, increasing the risk that their children inherit an autosomal recessive disorder.
However, there is another side to this.
As genetic distance becomes sufficiently large between diverged populations, reproductive compatibility can sometimes begin to decline.
This phenomenon is generally referred to as:
OUTBREEDING DEPRESSION
THE MOUSE STUDY
Two closely related subspecies of European house mouse can mate and produce hybrids.
However, when their genomes are mixed together, a substantial proportion of hybrid males develop fertility problems — even though most are not completely sterile.
Complete sterility was rare or possibly absent.
Most hybrid males apparently still produced sperm.
However, roughly 30% of hybrid males had either:
[]Unusually low sperm counts
[]Unusually small testes relative to body size
compared with the normal ranges observed in the two parental subspecies.
WHY WOULD MIXING THE TWO POPULATIONS CAUSE INFERTILITY?
This is probably the most important part.
Imagine the two populations originally came from the same ancestral population:
Ancestral mice
↓
Geographic separation
↓
Population A | Population B
↓
Geographic separation
↓
Population A | Population B
Once separated, the two populations begin accumulating different genetic changes.
Within Population A:
A genes + A genes → works
Within Population B:
B genes + B genes → works
There does not necessarily have to be anything "wrong" with either population.
Each genome works perfectly well within the genetic background in which it evolved.
The problem can appear when the two genomes are mixed.
Imagine Population A evolves a particular version of Gene X:
X₁
while Population B evolves a particular version of Gene Y:
Y₂
X₁ works perfectly well with the other genes found in Population A.
Y₂ works perfectly well with the other genes found in Population B.
But in a hybrid:
X₁ + Y₂ → disrupted sperm production
Neither mutation is necessarily harmful by itself.
The problem appears specifically when the two variants occur together.
Basically: genetic incompatibility.
WHY ARE SOME HYBRIDS FINE WHILE OTHERS AREN'T?
To understand this, imagine there are ten different genes that can potentially contribute to compatibility problems.
One hybrid might inherit:
A A A B A B A A B A
while another inherits:
B A B B A A B B A B
The exact combination matters.
Hybrid #1 might have:
[]Normal sperm count
[]Normal testis size- Slightly abnormal sperm
Hybrid #2 might have:
[]Low sperm count
[]Small testes
Hybrid #3 might have:
- Severe sperm-production problems
Hybrid #4 might be:
- Basically normal
And that is approximately what the researchers observed.
Rather than every hybrid developing the exact same sterility phenotype, fertility varied substantially between individual hybrid males and ancestry groups.
SIMPLIFICATION FOR LOW-IQ USERS
Some traits depend on huge numbers of genes working together properly.
Fertility is a perfect example.
Imagine sperm production depends on 100 different genetic components operating together like parts of a machine.
In Population A:
A1 + A2 + A3 + A4 + ... → WORKS
In Population B:
B1 + B2 + B3 + B4 + ... → WORKS
Most of those genes may be almost identical between the populations.
But perhaps a few have changed:
[]A17 differs slightly from B17
[]A42 differs slightly from B42- A86 differs slightly from B86
Within their own populations, these versions still work perfectly because the surrounding genes evolved alongside them.
But a hybrid might inherit:
A17 + B42 + A86
and that particular combination might not function as efficiently.
This is the basic idea behind genetic incompatibilities produced by population divergence.
SO WHAT'S THE IDEAL LEVEL OF RELATEDNESS?
This raises an obvious question.
If being too closely related can cause inbreeding depression, while being extremely genetically distant can sometimes produce outbreeding depression, is there an intermediate level of relatedness associated with maximum reproductive success?
This is where the Icelandic study becomes interesting.
THE ICELANDIC STUDY
Researchers examined the reproductive histories of 160,811 Icelandic couples born between 1800 and 1964.
They used Iceland's unusually detailed genealogical database, which contains information on approximately 95% of Icelanders born since 1700.
They found that reproductive success varied according to how closely related the parents were.
Couples who were second cousins or more closely related had relatively low reproductive success.
Fertility then increased as relatedness decreased, reaching its maximum among approximately:
THIRD- AND FOURTH-COUSIN COUPLES
After that point, however, reproductive success gradually declined again as couples became increasingly distantly related.
The same general pattern appeared when researchers counted not merely the couple's children, but the number of those children who themselves eventually reproduced.
Even the number of grandchildren showed a similar pattern.
In other words, reproductive success followed something resembling an inverted U-shaped curve:
VERY CLOSELY RELATED
↓
Lower reproductive success
↓
MODERATELY RELATED
↓
Highest reproductive success
↓
VERY DISTANTLY RELATED
↓
Reproductive success declines again
↓
Lower reproductive success
↓
MODERATELY RELATED
↓
Highest reproductive success
↓
VERY DISTANTLY RELATED
↓
Reproductive success declines again
BUT THERE'S AN OBVIOUS OBJECTION
Now a skeptic might say:
Maybe Icelanders who married third or fourth cousins simply belonged to different social groups than people who married genetically distant partners.
What if someone who left their home region to attend university met a partner from the opposite side of Iceland?
That person might also:
[]Marry later
[]Prioritize education
[]Have a different socioeconomic background
[]Live in a city- Intentionally have fewer children
So perhaps distantly related couples had fewer children because of social and demographic differences, rather than because greater genetic distance reduced fertility.
This is where the Danish study becomes relevant.
THE DANISH STUDY
Instead of reconstructing family trees and directly calculating how closely each husband and wife were related, the Danish researchers approached the question from another angle.
They used the geographic distance between the places where each partner came from as a rough proxy for genetic distance.
The logic is simple:
Historically, people whose families came from nearby communities were, on average, more likely to share ancestry than people whose families came from opposite ends of the country.
The researchers followed 22,298 Danish women born in 1954 who were still living in Denmark in 1969.
Their reproductive histories were then followed until the end of 1999 using Denmark's Central Personal Register.
The researchers compared each woman's fertility with the distance between her home parish and her husband's home parish.
If avoiding inbreeding were the entire story, you might expect:
Greater distance → greater fertility
But that is not what they found.
Instead, fertility initially increased as the geographic distance between the partners increased.
It eventually reached a maximum at roughly:
75 KM
After that point, fertility began to decline again as the partners' places of origin became increasingly distant.
So the pattern looked roughly like this:
EXTREMELY NEARBY
↓
Lower fertility
↓
MODERATE DISTANCE (~75 KM)
↓
Highest fertility
↓
INCREASINGLY FAR APART
↓
Fertility gradually declines again
↓
Lower fertility
↓
MODERATE DISTANCE (~75 KM)
↓
Highest fertility
↓
INCREASINGLY FAR APART
↓
Fertility gradually declines again
The obvious question is whether this was merely caused by social differences.
Maybe people who found partners farther away were more educated, richer, more urban, or simply had children later.
The researchers therefore examined several of these possible confounders.
The relationship could not be adequately explained by differences in:
[]Education
[]Family income
[]Urban versus rural residence
[]Mother's age at first birth
That makes the finding much more interesting.
Of course, geographic distance is not literally genetic distance.
But in historical populations, geographic distance often correlates with shared ancestry.
The results were therefore interpreted as being consistent with a pattern in which the benefits of escaping close inbreeding eventually give way to the possible costs of excessive genetic distance.
Too genetically similar
→ problems
Intermediate similarity
→ highest reproductive success
Increasingly genetically distant
→ reproductive success may begin declining again
→ problems
Intermediate similarity
→ highest reproductive success
Increasingly genetically distant
→ reproductive success may begin declining again
BANG YOUR THIRD COUSIN FOR IDEAL FERTILITY
or
bang someone who grew up ~75 km away.
Population-level observational findings are not literally a recommendation for choosing a partner.
or
bang someone who grew up ~75 km away.
Population-level observational findings are not literally a recommendation for choosing a partner.
Mouse hybrid fertility study
https://academic.oup.com/evolut/article-abstract/66/2/443/6851407
Icelandic/Danish relatedness and fertility research
https://www.science.org/doi/10.1126/science.1161907
https://academic.oup.com/evolut/article-abstract/66/2/443/6851407
Icelandic/Danish relatedness and fertility research
https://www.science.org/doi/10.1126/science.1161907
