|Chapter 13 - Genes|
|“Whatever advantage these genes [ASPM and MCPH1] give, some groups have it and some don’t. This has to be the worst nightmare for people who believe strongly there are no differences in brain function between groups."|
|Anthropologist John Hawks|
The race-deniers, who say there is no such thing as “race,” have a difficult time explaining why, when genetic differences of native populations across the world are mapped, the result is almost exactly the same as a map of the races. (Fig. 7-4). Thus, there is little doubt that genes differ among different populations.
All of the traits discussed in the previous chapters are caused, at least in part, by genes and, to that extent, “biology is destiny.” (Sigmund Freud). Only recently has genetics advanced to where some of the genes responsible for those traits have been identified, and only still more recently have racial differences in some of those identified genes been published. Although all humans have the same genes, the percentage of each population that has any given allele of a gene can vary from 0 (no one in the population has that allele) to 100% (everyone in the population has that allele, i.e., it is “fixed”).
It would be enlightening to present a table giving the world wide frequency of every important human allele that differs significantly between different populations, but that information is not yet available. Here are some genes for brain size and intelligence (Weiss, 1992; Plomin, 2004), behavior, skin, hair, and eyes, and diseases that are either already known to differ between populations or are very likely to differ.
The Brain and Intelligence
NBPF15 (“neuroblastoma breakpoint family, member 15,” aka MGC8902), Chromosome 1. This gene encodes multiple copies of the protein DUF1220, which is expressed in brain regions associated with higher cognitive function. Moreover, sequences of the gene are specific to different primates and, as the species become closer to humans, the number of duplicate copies increases to 212. (Popesco, 2006). Individual and racial differences in the number of copies have not yet been published.
DAB1 (“disabled-1”), Chromosome 1. This gene is involved in organizing the layers of cells in the cerebral cortex, the site of higher cognitive functions. A version of the gene has become universal in the Chinese, but not in other populations. (Williamson, 2007).
ASPM (“abnormal spindle homolog, microcephaly associated”), Chromosome 1. Its alleles affect the size of the brain; defects in the ASPM gene lead to small brains and low IQ. (Evans, 2004). A new ASPM allele arose about 5800 ya in Eurasia and that allele has been suspected of increasing intelligence in Eurasia; it is common in Eurasians but absent in Africans and chimpanzees. People who speak tonal languages (e.g., Chinese) are more likely to carry two newer alleles of ASPM and MCPH1 than people in non-tonal regions. (Dediu, 2007; Mekel-Bobrov, 2005).
SSADH ("NAD(+)-dependent succinic semialdehyde dehydrogenase"), Chromosome 6. The C form increases intelligence and lifespan; the T form is 20% less efficient. (Plomin, 2004; Binghom, J., "Clever people could live 15 years longer," Telegraph (UK), Aug. 23, 2008).
MCPH1 (“microcephaly, primary autosomal recessive 1”), Chromosome 8. The alleles of this gene, commonly called “microcephalin,” at least partly determine brain size and/or organization. (Wang, 2004). A new allele of this gene that increases intelligence arose about 37,000 ya (the confidence limit is very wide -- 60,000 - 14,000 BP; Evans, 2005). This allele is common in Eurasians but rare in Africans and absent in chimpanzees.
Both the newly-discovered ASPM and microcephalin alleles were strongly selected for and spread rapidly through the Eurasian populations. These genes have been associated chronologically with two of the most revolutionary changes in human affairs - an explosion of hand-crafts in the Upper Paleolithic era (40,000 ya), and the development of sophisticated cities and the beginning of major trade routes. 1 However, so far a correlation between IQ and the presence of these alleles has not been found. (Woods, 2006; Rushton, 2007a).
DCDC2 (“double cortin domain containing 2”), Chromosome 6. This gene affects the formation of brain circuits that make it possible to read. (Weiss, 2005). One allele can result in dyslexia. 2
NQO2 (“Homo sapiens quinone oxidoreductase2”), Chromosome 6. This gene clearly has effects on brain activity and might affect IQ, but that information and its population distribution are not yet published. 3
IGF2R (“insulin-like growth factor 2 receptor”), Chromosome 6. This was the first gene discovered for intelligence; possession of one of the alleles of this gene increases IQ by about 4 points. (Chorney, 1998).
DTNBP1 (“dystrobrevin binding protein 1”), Chromosome 6. It is associated with schizophrenia and has recently been linked to intelligence. (Burdick, 2006).
CHRM2 (“cholinergic receptor, muscarinic 2”), Chromosome 7, activates signaling pathways in the brain; some alleles can increase IQ 15 to 20 points. (Dick, 2007; Gosso, 2006).
FoxP2 (“forkhead box P2”), Chromosome 7. This gene affects language skills, including grammar, as well as IQ. Although many animals also have the gene, humans acquired an allele within the last 200,000 yrs that was strongly selected because the superior communications and creativity it made possible were a major advantage.
EMX2 (“Empty spiracles-like protein”), Chromosome 10, codes for the development of the cortex into specialized areas. Mismatched areas lower performance. (Leingärtner, 2007).
FADS2 (“fatty acid desaturase 2”), Chromosome 11, is involved in processing omega 3 fatty acids to produce nutrients for the brain. An allele of this gene raises the IQ of children by about 6 to 10 IQ points if they are breast-fed. (Caspi, 2007).
DARPP-32 (“dopamine- and cyclic AMP-regulated phosphoprotein”), Chromosome 17. One allele of this gene optimizes the brain's thinking circuitry, but increases the risk of schizophrenia. (Meyer-Lindenberg, 2007).
MAPT (“microtubule-associated protein tau”), Chromosome 17. Mutations in this gene can cause neurodegenerative disorders. The H2 haplotype of this gene may have come from the Neanderthals. (Hardy, 2005). Also, physicist and mathematician Roger Penrose proposed that consciousness is a quantum effect that arises in these microtubules. (Shadows of the Mind, 1996).
PDYN (“prodynorphin”), Chromosome 20. It codes for a precursor molecule for neuropeptides, which affects perception, behavior, and memory. (Balter, 2005).
HAR1 RNA (“human accelerated region 1”), Chromosome 20. This gene codes for an RNA protein that develops neurons in the neocortex of the brain. This gene is different in the brains of humans and chimpanzees and is rapidly evolving in humans. (Pollard, 2006). Also see HAR1F, which is active in special cells that appear early in embryonic development and help form the human cerebral cortex; HAR1 produces RNA that does not produce protein. (Smith, K., 2006; Pollard, 2006).
EST00083 (“expressed sequence tag”) is an mtDNA polymorphism found more often in high IQ groups. It is particularly common in Europe (less so in Asia), where it is associated with a lineage that dates back 35,000 yrs. (Thomas, 1998).
PER2 (period homolog 2, Dosophila), Chromosome 2, "is a key component of the mammalian circadian clock machinery." "[A] high and significant difference in the geographic distribution of PER2 polymorphisms was observed between Africans and non-Africans." (Cruciani, 2008)
ADH (“alcohol dehydrogenase”), Chromosome 4. Mutations in this gene cause Asians to have a more intense response to alcohol, including facial flushing. (Duranceaux, 2006).
PAX6 (“paired box gene 6”), Chromosome 11, controls development of the iris. A mutation of this gene is linked to impulsiveness and poor social skills, which is discernable by the appearance of the iris. (Larsson, 2007).
DRD4 (“dopamine receptor D4”), Chromosome 11, controls sex drive. (Zion, 2006). Some studies found that an allele is associated with novelty-seeking personality traits in two European populations (Benjamin, 1996), but other studies did not confirm this.
ACTN3 (“alpha-actinin-3”), Chromosome 11, codes for fast twitch muscle fibers. The R allele encodes a functional copy of the protein but the X allele does not produce the protein; 25% of Asian populations are deficient, 18% of Europeans, but less than 1% of the African Bantu population. (Yang, 2003).
AVPR1a (arginine vasopressin 1a receptor), Chromosome 12, influences social bonding and altruism in humans and some animals. People with a long promoter of the RS3 allele are more altruistic than persons with a short promoter. (Knafo, 2007).
ACE (“angiotensin I-converting enzyme”), Chromosome 17. It converts angiotensin I to angiotensin II, but is also involved in athletic ability. Racial differences are not yet known.
MAOA (“monoamine oxidase A”), X Chromosome. This gene codes for an enzyme which sits on mitochondrial membranes in neurons and degrades several important neurotransmitters, including several believed to be important in the regulation of aggression and impulsivity. (Moran, 2006). People with the short version of MAOA were found to be more violent and generally more antisocial than those with the long version. Also, people with low levels of the enzyme who were mistreated as children have significantly higher crime rates. (Moffitt, 2005; Meyer-Lindenberg, 2006). Different ethnic groups have different alleles. (Wikipedia, “Monoamine Oxidase”).
Skin, Hair,& Eyes
EDAR (“ectodysplasin A receptor”), Chromosome 2, controls hair thickness. East Asians have two copies of an allele that gives them thick hair. (Am. Soc. of Human Gen., Annual Meeting, Oct. 23-27, 2007).
MATP (“melanoma antigen transporter protein”), Chromosome 5, affects skin color. “The L374F mutation was present at an allele frequency as high as 0.96 in the German population, whereas it was completely absent in the Japanese population.” (Yuasa, 2004). There are at least 118 genes associated with skin pigmentation (Lao, 2007).
AIM1 (“absent in melanoma 1”), Chromosome 6, influences skin color. The 272K allele is common in Asian populations, such as Chinese (43.4%), Sinhalese (20.4%), and Tamils (12.1%), but is rare in Europeans (2.5%), Xhosans (Bushmen, 3.4%), and Ghanaians (4.1%). The 374F allele is exclusively found in Europeans (91.6%), but not in the other five populations (0%–1.9%). (Soejima, 2006).
TYR (“Tyrosinase”), Chromosome 11. This gene and the MATP gene have a predominant role in the evolution of light skin in Europeans but not in East Asians, who evolved light skin independently. (Norton, 2006).
KITLG (“KIT legand”), Chromosome 12. About 20% of the differences in pigmentation between people of African and northern European descent is due to different alleles of this gene. (Miller, 2007).
OCA2 (“oculocutaneous albinism II”), Chromosome 15. This gene can cause albinism, but the genetics are different in Caucasians and African Americans. (Lee, 1994). It also affects eye color. (Duffy, 2007).
HERC2, (“HECT domain and RCC1-like domain-containing protein 2”), Chromosome 15, can reduce the production of dark pigment (melanin) by adjacent gene OCA2, resulting in blue eyes, blond hair, and light skin; 97% of blue-eyed people have the same allele. The high frequency of the blue-eyed allele in Scandinavia implies that allele significantly increased reproductive success. (Eiberg, 2008).
SLC24A5 (“solute carrier family 24, member 5,” aka the “golden pigmentation gene”), Chromosome 15. An allele of this gene that changes a single amino acid in a protein plays a major role in giving Eurasians lighter skin than Africans. (Lamason, 2005). The European allele is not the same as the Asian allele. (Norton, 2006). This gene is also expressed in the brain. 4
MC1R (“melanocortin-1 receptor”), Chromosome 16. There are over thirty alleles for this gene. The gene helps determine hair and skin color, but not eye color. (Mueller, 2006). Africans (and tropical indigenous people in general) have an ancestral allele for this gene and only synonymous alleles (i.e., alleles that code for the same amino acids) of this gene; the alleles are ancient and code for eumelanin, which results in black skin and hair. (Harding, 2000). Europeans have alleles for blond, red, brown, and black hair.
KRT41P, aka KRTHAP1 (“keratin 41 pseudogene”), 5 Chromosome 17. This gene is present in chimpanzees, gorillas, and man, and codes for body hair. It was turned off in man about 240,000 ya. (Klein, 2002, p. 203).
EYCL1 (“eye color 1” aka “gey”), Chromosome 19, codes for green and blue eye color; EYCL2 (“bey1”), Chromosome 15, codes for brown eyes, and EYC3 (“bey2”), Chromosome 15, codes for brown and blue eyes. (Wikipedia, "Eye Color"). Five to ten genes may be involved in eye color.
ASIP (“agouti signaling protein”), Chromosome 20. The 8818G allele is associated with darker skin color in Africans and African Americans; since the allele also is found in African apes, it is “ancestral” in Africans. (Norton, 2006,).
Health & Disease
LCT (“lactase gene”), Chromosome 2, codes for lactase, an enzyme that catalyzes the digestion of lactose, milk sugar. An allele that enables adults to digest milk sugar arose in northern Europe only recently, between 5480 BC and 5000 BC. The allele was strongly selected and its possession by over 90% of northern Europeans may help explain how Indo-Europeans were able to spread so suddenly about 4000 ya. The vast majority of Asians and Africans do not have it, but the Tutsis more recently independently evolved a lactose-tolerant allele. (Burger, 2007). Since all children are lactose-tolerant and most adults are not, “lactose tolerance may be considered a form of neoteny.” (Wikipedia, “Lactose Intolerance”).
CCR5 (“chemokine (C-C motif) receptor 5”), Chromosome 3. The delta 32 deletion of this gene appeared more than 5,000 ya in southern Finland and may have provided some protection against smallpox. Today, only a small percentage of Europeans have this deletion (1%, though 10% of European Jews have it), but it protects them from the AIDS virus (Zimmer, 2001, p. 222-225), though it increases their risk of illness from flaviviruses, such as West Nile virus; it is not found in Asians or Africans. (Smith, 1997; Stephens, 1998).
PDE4 (“pyridoxine-dependent epilepsy”), Chromosome 5. An allele of this gene is involved in cardiovascular disease and lung cancer susceptibility. Blacks who smoke up to a pack a day are far more likely to develop lung cancer than whites who smoke similar amounts. Blacks may have less protection against lung cancer because they were subjected to less smoke, as fire is not needed as much in the tropics. (Garte, 2001).
CYP3A5 (“cytochrome”), Chromosome 7, acts to retain salt in the kidneys. It is common in Africans, who live in a hot climate where salt is lost through sweat and is not easily available. The CYP3A5*3 allele, which is non-functional, is far more common in Eurasians (96% for the Basques in the Pyrenees Mountains) than in Africans (6% in Nigeria). Thus, Africans who live in white civilizations retain too much salt, leading to cardiovascular problems. Another gene, AGT M235, which is also involved in salt retention, has a similar distribution. (Thompson, 2004; Roy, 2005).
CASP12 (“cysteinyl aspartate proteinase”), Chromosome 9. Having the non-functional version of this gene better prevents sepsis (infection of the blood and tissues by bacteria). The loss of function occurred 51,000 to 74,000 ya. (Wang, X., 2006). This gene HBB (“hemoglobin beta chain”) on Chromosome 11, codes for the beta strand of hemoglobin. A single copy of an allele of this gene protects against malaria, but two copies cause sickle cell anemia; 6 it is found mostly in people living in malarial regions of Africa and India.
CD4 (“cell development”), Chromosome 12. The 7R allele was probably very ancient in Neanderthals, but may be only 30,000 yrs old in Hss. It is a receptor for HIV. (Hanna, 1989).
BRCA1 (“breast cancer”), Chromosome 17. This gene has an allele that is involved in breast cancer. Of Ashkenazi Jewish women, 1 in 40 carries alleles of the BRCA1 and the BRCA2 gene that give them a 4 out of 5 chance of having breast cancer.
LTA4H (“leukotriene A4 hydrolase”), Chromosome 17. An allele of this gene increases the risk of a heart attack in African Americans by more than 250%, but only by 16% in whites and Asians. The gene boosts inflammation as a way to fight infections and is generally not found in Africans. Although 30% of whites have the allele, they have evolved other genes to counteract it, but the 6% of the African Americans, who acquired it by breeding with whites, have not. (Helgadottir, 2006).
APOH (“apolipoprotein H”), Chromosome 17. This gene is a major autoantigen for the production of antiphospholipid antibodies (APA) in autoimmune diseases. The APOH*3B allele is present only in blacks and is identical to the wild type APOH in chimpanzees. (Kamboh, 2004).
NOS2 (“nitric oxide synthase”), Chromosome 17, encodes an enzyme that produces nitric oxide. An allele possessed by Africans in malaria areas causes increased production of nitric oxide, which protects against the symptoms of the disease. Caucasians do not have that allele. (Keller, 2004).
CNDP1 (“carnosine dipeptidase 1”), Chromosome 18. A trinucleotide repeat sequence on this gene protects Caucasian Europeans, white Americans, and Arabs, but not blacks, from diabetic end-stage kidney failure. (Freedman, B.I., 2007).
APOE (“apolipoprotein E”), Chromosome 19. This gene plays a role in transporting cholesterol and is involved in Alzheimer’s disease. It is possible that some people may not have this gene at all which, if true, would raise some interesting questions. (Miller, 2006).
PDHA1 ("pyruvate dehydrogenase (lipoamide) alpha 1"), X Chromosome. The tree for this gene is estimated as 1.86 mya and the split between Africans and non-Africans as 200,000 yrs. There are no haplotypes shared between the Africans and the non-Africans and one site (544) is fixed in the non-African lineage (i.e., every non-African tested has the same allele, which suggests it is advantageous and ancient). (Harris, 1999.).
The reader may have noticed that genes that code for one trait may affect other, seemingly unrelated traits (e.g., PAX6, CCR5, and PAX6) and that some alleles (“ancestral” alleles) are found in blacks and chimpanzees, but not other races (NQ02, ASIP, APOH*3B, MC1R) or, vice versa, (ASPM, MCPH1).
Men and women differ by only a single chromosome (Y in men, X in women), yet the differences in that chromosome extensively affect their anatomy, physiology, and behavior. Figure 13-1 (Yang, 2006) shows how genes are expressed in the livers of female (top) versus male mice. Red corresponds to more gene expression, green to less. Even though one might think that the differences between males and females would be limited to reproduction-related differences on the X and Y chromosomes, this map shows that the differences have a large effect on genes that are expressed in the liver, which has little to do with reproduction. Thus, we should not be surprised if racial differences in genes affect much more in the body than the obvious differences in appearance.
At the present time, studies of racial genetic differ-ences have been mostly limited to mtDNA and coding nuclear DNA. Yet humans have more “junk” DNA than any other animal, and the functions of junk DNA are just beginning be discovered. Important racial differences can also be expected to be found in it as well, in the number of copies of genes, and in the gene regulators, the genetically-inherited “switches” that determine whether and when a gene is read.
Table of Contents
1. See (Evans, 2005) for Microcephalin and (Mekel-Bobrov, 2005) for ASPM. Back
2. (Meng, 2005). “The allele frequency of the A allele rs2274305 of the dyslexia-gene DCDC2 is about 0.28 among Eurasians and 0.99 among Yorubas from Nigeria, about 0.80 among African-Americans.” (Weiss, 2005). Back
3. “If we align the genetic code of Homo sapiens and the chimpanzee, Pan troglodytes, in both species NQO2 is coded by 231 amino acids. However, at the position 47 of rs2756081 [a particular allele] human Blacks are coding FF (phenylalanine) [the same] as chimps and a number of other mammals, and Eurasians with an above average IQ are coding LF or LL (leucine), [and] below IQ 100 FF.” “The allele frequency of the C allele rs2756081 of NQO2 is about 0.25 among Eurasians (0.41 in Tokyo in a sample, which is not in Hardy-Weinberg equilibrium) and 0.00 among Yorubas from Nigeria, about 0.02 among African-Americans.” (Strassburg, 2002). Back
4. (GeneCard for protein coding SLC24A5 GC15P046200). Back
5. A pseudogene is an inactivated gene. Back
6. When having two copies of the same allele, “AA” or “BB,” is disadvantageous compared to having one of each, “AB,” it is called “heterozygote advantage.” Right-handedness may be another example. (Corballis, 1991, p. 95). Back