Chapter 6: Down Syndrome may Be a Thrifty, Adaptive Response to Maternal Deprivation
“Without the relevant unifying concepts, comparative neurology becomes no more than a trivial description of apparently unrelated miscellaneous and bewildering configurational varieties, loosely held together by a string of hazy ‘functional’ notions.”
Hartwig Kuhlenbeck
| Down Syndrome Defined: |
| Down syndrome is a genetic disorder caused when abnormal cell division results in an extra copy of chromosome 21. This extra genetic material causes the developmental changes and physical features of Down syndrome. Down syndrome varies in severity among individuals, but generally causes lifelong intellectual disability and developmental delays. Early intervention and special education programs can help children with Down syndrome develop the skills needed to live independently. Mild to moderate cognitive impairment Delayed language development Short stature Distinct facial features |
Does Down Syndrome Have a Place in the Natural Order?
Contrary to the prevailing view of Down syndrome as pathological, this chapter explores whether Down syndrome could have been favorable within deprived environments in human or protohuman history. Certain metabolic and cognitive traits of Down Syndrome might have allowed them to be less reliant on maternal investment. A small advantage during adversity could have increased the incidence of trisomy 21 over time. Like other forms of predictive, adaptive responses, the propensity for having a baby with Down syndrome is genetic [1,2], with an increased likelihood of Down syndrome when both the mother and father are genetically predisposed.
Down Syndrome at a Glance
Down syndrome affects millions of individuals the world over. It is the most common identifiable cause of intellectual disability, accounting for nearly one-third of all diagnosed cases. With an incidence of 1-2 in 1,000 births [10], it is intriguing from an evolutionary standpoint. Also known as trisomy 21, it is the single most frequent autosomal trisomy in liveborn babies and the most frequent chromosomal abnormality in children.
Figure 1.1 A laboratory produced image of the complete set of chromosomes arranged in numerical order from a single individual. All of these chromosomes are isolated from a single cell. Such an image is called a karyotype. This karyotype reveals the presence of Down syndrome because of the three versions of chromosome 21.
Down syndrome was first recognized and described by British doctor Langdon Down in 1986 [6]. This was many years before geneticists uncovered that the syndrome is caused by trisomy of the 21st chromosome. A trisomy involves a failure of a pair chromosomes to separate (chromosomal non-disjunction) causing offspring to inherit three copies of the same chromosome instead of two. The trisomy usually occurs during cell division (meiosis) when a mother is generating eggs (oogenesis). In Down syndrome, this happens with the 21st chromosome, resulting in “trisomy 21,” where the organism has an extra (third) chromosome 21 within each cell [7]. The syndrome is caused by having three copies of the genes on chromosome 21, rather than the usual two. Sometimes, rather than a trisomy of the entire chromosome, only a segment of it is repeated, other times there is a mosaic of segments that are repeated, and just under 10% of the time the trisomy happens within the fathers body and affects the sperm. Advanced maternal age remains the largest risk factor in non-disjunction [8], although several others have been reported in the last few decades.
Figure 1.1 shows a sperm cell and egg cell from the parents. When the first egg cell divides it exhibits trisomy 21 where one daughter cell has no version of chromosome 21 and the other daughter cell has two. When it is fertilized by a normal sperm with a single copy of chromosome 21, the zygote ends up with three copies of the chromosome. This is passed on to all the fetal cells during development.
People with Down syndrome usually have flexible ligaments, a small chin, a small mouth, and a large protruding tongue that can interfere with speech. They also have altered facial appearance (craniofacial dysmorphology) and tend to breathe through their mouths. For example, they have small noses, mouths, and ears. Their eyes tend to be almond-shaped with white spots on the colored parts of the eye (iris), and a skin fold covering the inner corner of the eye (epicanthic folds). They also have flat, round faces, low-set ears, stocky builds, and slightly bent pinky fingers. Individuals with Down syndrome have a lower risk of all major solid cancers, including those of the lung, cervix, and breast. This low risk is thought to be due to an increase in the expression of tumor suppressor genes present on chromosome 21. Many of these distinctive features may be arbitrary or coincidental but other features may be ecological.
The average height for men is 5 ft 1 in, and for women is 4 ft 8. This reduced height is reminiscent of psychosocial short stature and the accompanying cognitive deficits brought on by severe childhood stress that we discussed in Chapter 2. If Down syndrome is a response to deprivation as this chapter will claim, then it is consistent with this pattern we have been discussing where reduced cognition may be an adaptive response to severe neglect.
Older Mothers are More Likely to Have Children with Down Syndrome
There is a strong relationship between maternal age and Down syndrome [1]. As a mother grows older, her propensity to conceive and deliver children with Down syndrome increases quickly, from one in one thousand at age thirty to one in eleven at age fifty [11]. An older mother is more likely to die before providing the parental investment necessary to produce socially and ecologically self-sufficient offspring.
It is well recognized in anthropological literature that the human foraging niche is extremely cognitively demanding and skill intensive and that self-sufficiency requires extensive maternal care and instruction [12]. This maternal age effect may allow Down syndrome to create a precocial and energy-efficient phenotype for children statistically likely to be born to a mother who will not live to provide sufficient investment and resources.
Middle-aged female dogs have the largest litters because their bodies are best prepared to do so. Older dogs are much more likely to have smaller litters. This reflects an age-related investment tradeoff and may be analogous to what we see with the maternal age effect with Down Syndrome. Down syndrome babies have smaller heads and smaller bodies. This would have made it easier for older women (who are more prone to infection and death from childbirth) to give birth without obstetric complications.
The following table presents the frequencies of trisomy 21 by maternal age. Please note that the probability of trisomy 21 increases with maternal age at a rate that is nearly three times that of all other chromosomal abnormalities combined. This relative rate increase is consistent with the hypothesis that trisomy 21 might be preferentially selected to be linked with advanced motherhood.
| Maternal Age | Frequency of Down Syndrome | Frequency of Any Chromosomal Abnormality |
| 20 | 1 / 1667 | 1 / 526 |
| 24 | 1 / 1250 | 1 / 476 |
| 30 | 1 / 952 | 1 / 384 |
| 35 | 1 / 385 | 1 / 192 |
| 40 | 1 / 106 | 1 / 66 |
| 45 | 1 / 30 | 1 / 21 |
| 48 | 1 / 14 | 1 / 10 |
| 49 | 1 / 11 | 1 / 8 |
Table 1: Frequency of Down syndrome and other chromosomal abnormalities by maternal age [11 & 13]
It is also interesting to note that the maternal age effect does not increase after age 49 [10]. This suggests a reproductive strategy for the following reason: The year of abatement in the maternal age effect seems to correspond with both the average age of menopause (between the ages of 40 and 58 with an average of 51)[14] and the average life expectancy for modern hunter-gatherer groups, as seen in the table below. In other words, mothers in the ancestral environment died around age 50, so there would be no selective pressure to further increase the rate of Down syndrome conceptions after this age. If Down syndrome was simply pathological and due to increasing germ cell mutations over time, we might expect the frequency of trisomy 21 to continue to grow after age 49, but it does not.
| Group | Average Age at Death (Terminal Age) |
| Hadza Female | 54.7 |
| Hadza Male | 52.4 |
| Hiwi Female | 51.3 |
| Hiwi Male | 51.3 |
| !Kung Female | 56.5 |
| !Kung Male | 56.5 |
Table 2: Life span parameters for human hunter-gatherers. [15-17]
The following table presents the frequency of trisomies for each chromosome among miscarriages (spontaneous abortions) and live births. This table shows that trisomy 21 is, by far, the most frequently occurring trisomy among live births.
| Chromosomal Trisomy | Number Among Miscarriages | Number Among Live Births |
| 1 | 0 | 0 |
| 2 | 159 | 0 |
| 3 | 53 | 0 |
| 4 | 95 | 0 |
| 5 | 0 | 0 |
| 6-12 | 561 | 0 |
| 13 | 128 | 17 |
| 14 | 275 | 0 |
| 15 | 318 | 0 |
| 16 | 1229 | 0 |
| 17 | 10 | 0 |
| 18 | 223 | 13 |
| 19-20 | 52 | 0 |
| 21 | 350 | 113 |
| 22 | 424 | 0 |
Table 3: Most chromosomal trisomys result in miscarriage but three of them can result in life births. [18]
It is also important to note that it has been shown that the trisomies associated with maternal age may not be due to germ cell mutations or an increased rate of non-disjunction during conception. A review of studies on the effects of maternal age on trisomy 21 conceptions written by Raymond Kloss and Randolph Ness suggests that the origin of the trisomies lies not with an increase in the number of non-disjunctions but with a decrease in rejection of trisomy zygotes. The authors state that this finding suggests that the pronounced association between trisomy 21 and maternal age is indicative of a “reproductive strategy” because it is not simply due to the accumulation of germ cell mutations with age [19].
This would not be the first hypothesis to claim that natural selection makes non-disjunction (or chromosomal aneuploidy) in an animal chromosome more frequent. The nematode roundworm (Caenorhabditis elegans) is a species that reproduces through self-fertilizing hermaphrodites. However, this worm can produce functional males by employing chromosomal non-disjunction [3-5]. This worm is thought to have adopted the male body plan to use sexual (as opposed to asexual) reproduction to increase genetic (allelic) diversity. The qualities of the Down syndrome body plan may be analogous to those of the C. elegans male in that they respond to specific environmental contingencies and use non-disjunction to provide an adaptive advantage.
Some but not all forms of syndrome intellectual disability show some association with the advanced age of one of the parents. For example, the chromosomal abnormality (uniparental disomy) responsible for Angelman and Prader Willi syndromes is also associated with advanced maternal age. These disorders also feature a potentially adaptive tendency toward obesity and low metabolic rates.
Many animals give birth to litters of multiple offspring. It is common in many species to have a member of a litter that is significantly smaller and weaker that may have a lower metabolism. These members are sometimes colloquially called runts. It is common for runts to have cognitive deficits and other developmental delays. Runts often do not survive infancy because of failure to thrive, competition with siblings, or rejection by their mothers. However, these individuals often survive to adulthood and live to reproduce normally. Runts exist because of material and energy tradeoffs the mother makes to maximize her reproductive potential. Down syndrome, like other forms of intellectual disability discussed in the last chapter, may exist for similar reasons.
Risk Factors that May be Adaptively Tied to Down Syndrome
Other risk factors, aside from maternal age, link Down syndrome etiology with maternal deprivation. A cluster investigation reported that a short pregnancy interval is a risk factor for Down syndrome [20]. As discussed in the previous chapter, it is logical to conclude that mothers with more than one baby in a short time interval would be statistically less likely to provide adequate maternal care because their time and resources would be divided. Furthermore, one would expect that a mother providing sufficient care to the baby she has already invested in previously might not be able to provide adequate care to subsequent offspring.
Other reports have strongly associated the absence of a menstrual cycle (anovulatory activity or amenorrhea) followed quickly by conception with increased occurrence of Down syndrome [21,22]. These findings can be interpreted similarly. The absence of a menstrual cycle is usually caused by stress, starvation, previous pregnancy, or lactation. It is conceivable that this effect may have been selected because of the difficulty associated with allocating maternal investment to two closely spaced infants. This epidemiological data frames Down syndrome as part of a quantitative reproductive strategy.
Additional maternal factors associated with maternal deprivation are linked with Down syndrome conception. For instance, mothers of Down syndrome children have been shown to have more significant illnesses before conception, especially psychological illnesses [23]. A mother suffering from anxiety or a psychological condition is probably more likely to deprive her offspring of sufficient maternal care. Similar to schizophrenia it is thought that Down syndrome development is highly complex involving environmentally induced epigenetic modifications, gene-environment, and gene-nutrient (especially the vitamin folate) interactions (Coppede, 2016).
Another interesting pattern is derived from reports that have found an association between the risk of Down syndrome and the advanced age of the maternal (yet not paternal) grandmother at the mother’s birth (after correction for maternal age) [24,25]. There is growing consensus in the anthropological literature that the presence of a maternal grandmother [26,27] has a variety of positive effects on a forager child’s survival likelihood, rate of productivity, and life expectancy [28,29]. If the maternal grandmother is old at her daughter’s conception, then it follows logically that she is likely to be quite old at the time of her grandchild’s conception. It would also follow logically that an older grandmother would be less likely to provide grandparental investment before she dies. Thus, Down syndrome may be an adaptive response to diminished maternal and grandmaternal investment.
The Adaptive Properties of Down Syndrome
Down syndrome babies have a very low metabolism which might have conferred them an ability to conserve calories and thus avoid starvation in the environment of evolutionary adaptedness. They would have been much easier for older, stressed, or burdened mothers to rear. Reports have shown that the resting metabolic rate of both children and adults with Down syndrome is significantly lower than those of matched, non-trisomic individuals [30,31]. It is estimated that they use 10 to 15% less energy when at rest than peers of the same size, age, and gender. Down syndrome is strongly associated with decreased muscle tone, which may partially explain the lowered metabolic rate. Decreased thyroid hormones observed in Down syndrome [32] may also be responsible. Low metabolism is thought to partially explain the high proclivity for obesity in Down syndrome groups as observed in modern times [33]. This genetic propensity for energy conservation probably only translates into obesity in modern times and may have protected Down syndrome individuals from starvation in ancestral times.
It is well established that the brain and nervous tissue generally are very metabolically expensive [34]. The mass-specific metabolic rate of brain tissue is over 22 times the mass-specific metabolic rate of skeletal muscle [35]. The small brain size seen in Down syndrome individuals may, in fact, be an advantageous decrease in this metabolically expensive organ. Brain volume and weight are well documented to be diminutive throughout the maturational timeline in Down syndrome individuals [36,37]. A study limited to adults determined that the average brain weight in Down syndrome adults is 76 to 82% of the usual [38]. The average IQ is around 50 points, equivalent to an eight or nine-year-old child, but varies from 20 to 70. People with Down syndrome generally understand language better than they can produce it. Because they have good hand-eye coordination, learning sign language is usually an option, although the majority speak intelligibly.
The hippocampus volume is significantly smaller in Down syndrome subjects than in normal comparison subjects, even when total brain volume is controlled [39-42]. Decreased hippocampal volume in Down syndrome may be evidence of an adaptive neuroanatomical alteration to reduced ecological demands encountered by Down syndrome individuals in the ancestral environment. As we have seen in previous chapters, the hippocampus is known to respond plastically to ecological demands in mammals and birds. Reductions in its size are consistently interpreted as predictive, adaptive responses to food scarcity and environmental deprivation [43-45].
A study by Becker et al., which concentrated on the visual cortex, reported that the dendritic “tree” in infants with Down syndrome was more advanced than in normal infants (Becker et al., 1986). However, by two years of age, the dendritic branches within the cortex were significantly shorter and fewer in number. These findings are consistent with the idea that the Down syndrome dimorphism (dimorphic variant) is an altricial strategy where lots of simple learning occurs early but that this then reverses.
Down syndrome and many other heritable forms of intellectual disability are associated with increased distance between the eyes (hypertelorism) [46].
It makes sense that an MR individual would be less susceptible to ambush if they had more expansive peripheral vision. Wider-set eyes prove less valuable for hunters and more valuable for prey. Animals that remain vigilant and scan for predators, like mammalian herbivores, reptiles, amphibians, and fish, also exhibit widely spaced eyes. Their eyes can be near the opposite sides of their heads. We know that Down syndrome humans have working memory and attention deficits. It makes sense that they might forgo the benefits of closely set eyes (hypotelorism) because they would be less likely to benefit from chase hunting, tool making, or close perceptual work.
Many individuals with Down syndrome develop dementia similar to Alzheimers by their 40s marked by senile plaques and neurofibrillary tangles. After the age of 50, the risk of developing dementia is around 70%. This may be due to the triplication of genes known to be involved in Alzheimer’s pathology including the amyloid precursor protein (APP). Accumulation of amyloid beta can be observed as early as eight years old in Down syndrome. Chapter X characterizes this accumulation as an energy saving mechanism and discusses how Alzheimer-like neuropathology develops in the brains of starving mammals to help them save energy.
There has been research looking into the mystery of how Down syndrome individuals can survive and reach old age despite the handicap of having an entire extra chromosome containing 200 to 300 genes. It would be expected that an extra chromosome would create a fatal gene dosage imbalance. Researchers have concluded that the Down syndrome genome contains special regulators that diminish the over expression of genes from the extra chromosome making it possible to compensate for the surplus induced by the third copy of chromosome 21 (Popadin et al., 2018). They found that gene expression seems to be carefully regulated at the levels of gene variation, regulation, and expression hinting at the possibility that natural selection may have played a role in tuning Down syndrome developmental viability.
Popadin K, Peischl S, Garieri M, Sailani MR, Letourneau A, Santoni F, Lukowski SW, Bazykin GA, Nikolaev S, Meyer D, Excoffier L, Reymond A, Antonarakis SE. Slightly deleterious genomic variants and transcriptome perturbations in Down syndrome embryonic selection. Genome Res. 2018 Jan;28(1):1-10.
It is also interesting to note that Down syndrome individuals have a few strange phenotypic traits that may have analogs or homologs in chimpanzee morphology. Down syndrome individuals are likelier to have small noses and flat faces, and a flat nasal bridge, characteristics of apes and ancestral hominids. They also have a larger space between big and smaller toes [46]. This gap between the big toe and the toes next to it is a trait seen in apes and monkeys called the sandal gap and plays a role in using the feet to grab branches. Perhaps even more intriguing, Down syndrome individuals are much more likely to have a single palmar crease. This means they only have one line separating their four fingers from their thumb, whereas most people have two. This is sometimes called the “simian crease” because apes and many monkeys also have this trait [46], but very few non-trisomic humans have it. Down syndrome individuals also have anomalous dentition, characterized by smaller teeth [47]. In other animals, small teeth are evidence of a diet of fruit (frugivorous) or insects (insectivorous). These throwback (atavistic) traits and the genes responsible for them may have paleoanthropological or phylogenetic significance.
Down Syndrome Results in a Thrifty Phenotype
Down syndrome individuals are susceptible to metabolic disorders like those discussed in Chapter X. The close association of fitness-compromising diseases, including diabetes [49], heart disease [50-52], and obesity [53-55] with Down syndrome may well have influenced some researchers to reject the idea that Down syndrome may be an adaptive phenotype. I have three arguments against such criticism. First, the disabilities are not all that potent. Medical experts advise parents to raise Down syndrome children the same way they would raise non-Down syndrome children. Down syndrome children are screened for the diseases they are more susceptible to, such as heart disease. Table 5.1 below lists some of the diseases that most commonly present with Down syndrome. Still, most Down syndrome individuals can expect to live a moderately healthy life.
| High Risk Disorders in DS | Approximate Rate |
| Hearing Loss | 50-75% |
| Obstructive Sleep Apnea | 50-75% |
| Ear Infections | 50-75% |
| Eye Diseases | 50-60% |
| Eye Issues Requiring Glasses | 50% |
| Heart Defects at Birth | 50% |
| Thyroid Disease | 4-18% |
| Anemia | 3% |
| Iron Deficiency Anemia | 10% |
| Leukemia | 1% |
| Hirschsprung Disease | <1% |
Table 5.1: Children with Down Syndrome are at a higher risk of being affected by certain disorders than children without.
Second, the Down syndrome phenotype may have produced adaptive benefits for a more ancient ancestor. Since then, the phenotype may not have been exposed to equally purifying selection allowing the accumulation of deleterious mutations. In biology, an atavism is the recurrence of traits from an ancestor in a subsequent generation. If Down syndrome is atavistic we can expect some of the traits to be adaptive and others to be maladaptive. If it was the case that millions of years have passed since it was adaptive, then the genetic changes that humanity has undergone in the last two million years may have undermined its beneficial qualities especially given that the selective pressures on humanity have changed greatly since this time.
My third response to the anticipated criticism points out that the “pathological” disorders that regularly accompany Down syndrome today may have actually increased reproductive success for Down syndrome individuals. These disorders, diabetes, heart disease, and obesity, are the three facets of the thrifty phenotype phenomenon [57,58]. As you know, according to the thrifty phenotype hypothesis, phenotypes that are programmed prenatally (by nutritional deprivation) to express low metabolic rates are thought to enjoy a survival advantage under deprived circumstances. However, if such a thrifty fetus is born into an environment marked by nutritional abundance, it will face an increased risk of the metabolic syndrome, including diabetes, heart disease and obesity [59]. The genes that cause Down syndrome individuals to be susceptible to diabetes, heart disease, and obesity in modern times may have protected them from starvation and famine, during ancestral times, via the mechanisms proposed by James Neel [60,61] and David Barker [62-64].
Down syndrome individuals also have suppressed immune systems and susceptibility to respiratory infections [65], yet this may be adaptive for their niche if we envoke the concept of embodied capital. Embodied-capital theory sees growth, development, and maintenance as investments in somatic capital.
A great deal of “embodied capital” or scarce resources are invested in the immune system. The less active immune system in Down syndrome individuals may be another example of thrift.
Sex and Reproduction in Down Syndrome
It is challenging to find precise information about Down syndrome reproductive fertility. However, it is recognized that most Down syndrome females are fertile. Half of the conceptions of a Down syndrome female are normal, without trisomy 21. Most Down syndrome males are subfertile [66]. However, there are medical reports of Down syndrome men fathering children (Pradhan et al., 2006; Sheridan et al., 1989). There is even an anecdotal case where a Syrian man with Down syndrome married a woman without Down syndrome, and they had a son without Down syndrome who became a doctor named Sader Issa. Sader says that his father was loving, helpful, a hardworking breadwinner, and a pillar of the community.
The reduced fertility in males is thought to be due to issues with sperm creation but may be related to reduced opportunities for sexual activity. It is reasonable to assume that Down syndrome males would encounter some difficulty finding sexually receptive females. This may be related to why males with Down syndrome dedicate less energy to fertility. In contrast, Down syndrome females probably would not have difficulty finding receptive males. This is evidenced by the fact that Down syndrome females in modern times are frequently preyed upon sexually by non-trisomic males [67,68]. One study reports that 72% of sexual abuse victims that are mentally disabled are women and that the majority, 88%, of perpetrators are men [69]. These facts imply that Down syndrome females might have been the driving force behind the selection for trisomy 21 because their progeny would have carried genes for increased proclivity. The less fertile males, though, may still have increased their inclusive fitness by aiding their close kin, alloparenting, or achieving covert copulations [70].
Many forms of syndromic intellectual disability, including Down syndrome [66], are associated with hypogonadism (low testicular mass), which is thought to be related to the reductions in fertility seen in some of these groups. Testosterone, the hormonal product of the male gonads, is well known to be a powerfully anabolic hormone and, as we have seen, Down syndrome physiology seems to feature diminished anabolism in the form of insulin resistance [49] and growth hormone paucity [71]. It is known that mammals, responding plastically to starvation to reduce energy expenditure, often diminish their use of anabolic hormones. One way they accomplish this is by suppressing gonadal function, which reduces the energy spent on fertility and reduces the anabolic effects of sex hormones [72,73]. The suppression of gonadal function in Down syndrome may be a similar adaptive trait.
Down syndrome males may not have been subfertile in preagricultural times. The widespread, almost ubiquitous obesity seen in Down syndrome males, which indeed would not have been present in the ancestral past, may be exacerbating the susceptibility to diminished fertility. In fact, obesity is well known to decrease testosterone levels and is a significant risk factor for infertility in non-trisomic males [74-76]. Furthermore, reproductive isolation can occur rapidly due to evolutionary changes. This may be true of infertility too. Individuals with Down syndrome may have been much more fecund and virile in the past.
Down Syndrome-like Conditions in other Primates
Somewhere in the human past since we diverged from the other great apes, two ancestral chromosomes fused to form human chromosome 2. This is why the great apes have 48 chromosomes but humans only have 46. This is also why chromosome 22 in apes corresponds to chromosome 21 in humans. Trisomy 22 has been identified in chimpanzees, orangutans, and gorillas. Fascinatingly, it leads to behavioral and developmental symptoms very similar to trisomy 21 in humans. It is unknown how common the condition is in chimps because there are fewer than 300,000 chimps on the planet and scientists are not looking for trisomic animals. However, experts predict that it could be roughly as common as Down syndrome in humans (Hirata et al., 2017). Knowledge of a form of Down syndrome in the apes brings into question whether Down syndrome was adaptive in humans, apes, or some species that preceded them. Something like it may even exist in monkeys.
A trisomic female rhesus monkey named Azalea was born to a 21-year-old mother. This is an advanced maternal age for rhesus monkeys. Azalea displayed moderate cognitive deficits. Primatologist Frans de Waal commented, “we knew within several days that she wasn’t completely normal. She’s healthy and well-accepted by the group, but she is also much slower at learning, and she is much less active socially than other monkeys.” When they investigated the cause they uncovered that Azalea had a trisomy. Interestingly, Azalea was well-tolerated when she made social mistakes, such as threatening dominant individuals. Because any other monkey would have been punished, this told researchers that monkeys have a form of “empathy” for mentally disabled individuals. Perhaps humans in the prehistoric past had similar empathy and were willing to go out of their way to excuse or even provide for Down syndrome individuals, thereby increasing their reproductive success.
Chinese Human Genome Center has spent much time studying the genomic divergence between humans and primates primarily because, as they assert, it “may provide insight into the origins of human beings and the genetic basis of human traits and diseases.” The researchers compared the genes on the 21st chromosome in humans to the corresponding genes of chimpanzees, orangutans, gorillas, and macaques. The findings of one study [48] identified the number of nucleotide differences and the differences in the coding promoter and exon-intron junction regions between humans and apes. Using a bioinformatics-based approach, they concluded that the discrepancies between the genes found on human chromosome 21 and the genes located on the homologous regions in chimpanzees suggest that chromosome 21 arose due to the presence of “purifying selection.” They do not fail to point out that the genes responsible for Down syndrome are located on the 21st chromosome, the smallest chromosome, which seems to contain a relatively small number of genes.
Another genetic study revealed that the “Down syndrome critical region” (DSCR) on chromosome 21, which may contain genes responsible for many features of Down syndrome (DS), seems to have been highly conserved in great apes (Luke, 1995). Other genetic probes should be used to see if and how this region has been evolutionarily conserved and protected from disadvantageous mutations through primate phylogenetic history.
Luke S, et. al. 1995. Conservation of the Down syndrome critical region in humans and great apes. Gene. 161(2): 283-5.
There are reports of macaque monkeys with trisomy 18 that show Downs-like symptoms that socialize normally and get along well with members of their troop (Swartz & Sackett, 1994). Another trisomic monkey named Monu lived to have five healthy babies. These findings indicate that scientists should scrutinize chromosomal aneuploidies in various species and ascertain if they could be adaptive polymorphisms that respond to particular life history contingencies such as being born to an older mother.
Because of prenatal screening, around 90% of fetuses diagnosed with Down syndrome today are aborted. I don’t think it is wrong to terminate a Down syndrome pregnancy. But I certainly don’t think keeping a baby with Down syndrome is wrong either. Many parents believe that if they had aborted their Down syndrome baby, they would have been making a horrible mistake. Most parents report bonding normally and even strongly with their Down syndrome children. In many ways it is a beautiful condition.
Individuals with Down syndrome are often charming, sweet, and rarely spiteful. Many experts note that they are commonly extraordinarily loving and generally happy (Margulies, 2007). A recent Vanderbilt Kennedy Center study published data found that families with a child with Down syndrome have lower divorce rates. People with Down syndrome often have intact emotional intelligence. They also seem to have enhanced empathy, cooperation, and emotional regulation. Their general tendency to be social and easy going has led to hypotheses that Down syndrome is an evolutionary trade-off between cognitive and social abilities.
People with Down syndrome can make very perceptive intuitive judgments and generally learn to read and write. Most adults that were schooled as children can read at a 3rd to 4th-grade level. They can learn to speak multiple languages. They can also usually learn to play instruments, read music, and speak multiple languages. Many can be mainstreamed in school and in physical education. If you watch a few minutes of Down syndrome athletes online, you may be surprised at the athleticism and agility they are capable of. I train in various sports, but I am humbled when watching the Special Olympics. If someone with Down syndrome worked to develop proficiency at a certain sport from a young age, they will probably be far better at that sport than you are. For example, I have trained in tumbling and gymnastics for years, but I cannot begin to compare to the Down syndrome gymnasts I have seen. Observing them really helped me grasp the reality that I would not be able to survive in the wild as well as a prehistoric person with Down syndrome that has been foraging all their life.
People with Down syndrome can get married, attain driver’s licenses, and even hold jobs, especially if given the right encouragement and support. In the United States, about 20% do paid work in some capacity. A rising number of adults with Down syndrome are living on their own with limited assistance from family members or the government. A small percentage can live entirely independently.
They don’t live as long, but the average life expectancy is almost 60, and they can live into their 80s.
An objection to the present hypothesis might point out that Down syndrome individuals are not strong or clever enough and thus would have been conspicuously defenseless in savage, prehistoric times. Australopithecines, a vastly successful hominid group that survived for over two million years despite their tiny frames, would have had brains less than half the size of Down syndrome individuals and yet they lived successfully for hundreds of thousands of years. The next chapter will look more closely at human ancestors and propose some parallels between them and some modern neurodivergent groups today.
Conclusion
The concept of the thrifty phenotype has become an increasingly emergent theme in medical science, and it has profoundly impacted the viewpoints assumed by pathologists. It has become well accepted that certain disorders can be programmed by differential gene expression resulting in a phenotype that is parsimonious with energy expenditure. The epidemiological associations with advanced maternal age, short interbirth intervals and amenoreah combined with the metabolically conservative traits seen in individuals with Down syndrome imply that it may well represent an adaptive, thrifty phenotype. It is evident that much more work is needed to define the parameters of the relationship between Down syndrome and human reproductive strategy.
Chapter Summary
- Individuals with Down syndrome may have been well suited for a deprived environment. Down syndrome may represent a predictive, adaptive response to severe maternal deprivation.
- Trisomy of the 21st chromosome before or at conception is responsible for Down syndrome. It is known to increase in incidence with advanced maternal age.
- One out of eleven mothers over the age of fifty conceives a Down syndrome baby, compared to one in one thousand at age thirty.
- This chapter emphasizes that an older mother is more likely to die before she can provide the parental investment necessary to produce an ecologically self-sufficient offspring. Prolonged maternal investment is essential for hunter-gatherers to master the skill-intensive food procurement techniques they will need to become independent of their mothers.
- Because Down syndrome individuals are much more likely to be born to older mothers, they must have been routinely deprived of maternal investment during prehistory. Over time, this consistent paring of maternal deprivation to trisomy 21 conceptions may have caused natural selection to favor genes responsible for the energy-conserving traits seen in modern-day Down syndrome.
- These traits include muscle hypotonia, decreased cerebral metabolism, decreased hippocampal volume, a strong propensity for obesity, and growth hormone and thyroid hormone paucity.
- Such a “thrifty phenotype” may have allowed Down syndrome individuals to become independent of their mothers at a far earlier age and allowed them to forgo the skill-intensive ecological niche that non-trisomic humans are phenotypically suited for a less cognitively and physically rigorous one.
Pradhan M., Dalal A., Khan F., Agrawal S. 2006. Fertility in men with Down syndrome: a case report. Fertility and Sterility. 86 (6): 1765-1765.
Sheridan R, Llerena J Jr, Matkins S, Debenham P, Cawood A, Bobrow M. Fertility in a male with trisomy 21. J Med Genet. 1989 May;26(5):294-8.
Argue D, Groves CP, Lee MSY, Jungers WL. The affinities of Homo floresiensis based on phylogenetic analyses of cranial, dental, and postcranial characters. J Hum Evol. 2017 Jun; 107:107-133.
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