Neanderthals had ancestral Microcephalin gene

Evans et al. had previously proposed that the derived MCPH1 allele had entered the modern human gene pool by Neandertals. This paper tests this by looking at a 50,000 year BP Neandertal, finding them to have the ancestral allele, thus weakening the case for introgression.

The authors write:

Evans and colleagues proposed that haplogroup D originated from a lineage separated from modern humans for 1.1 million years and introgressed into the human gene pool by 37,000 years ago, probably from a Neanderthal stock [4].

However, simulation approaches have shown that two key hypotheses of this model, namely positive selection and admixture, can be relaxed as long as Eurasia was settled from an African population that was both subdivided and under expansion [5]. Interestingly, variation in neurocranial geometry have recently suggested significant levels of geographic structure among early modern humans from Africa [6]. In addition, no direct empirical evidence supports a third key component of the model, ie. that Neanderthals carried alleles of the D haplogroup.

This is a great paper in view of the recent controversy about modern human-Neandertal admixture. I have been on the skeptic camp, and this certainly strengthens my African structure thesis.

Here is how the authors try to explain the deep divergence between the ancestral and derived haplotypes:

There is a broad agreement that the contribution of archaic Homo populations to the modern gene pool, if any, must have been very limited [33], [34]. Different lines of evidence concur to suggest that the dispersal of anatomically modern humans from Africa was accompanied by repeated founder effects [35]–[38]. If these founder effects were drastic, most or all gene genealogies should actually be shallow, and hence the occurrence of ancient splits would imply some degree of introgression from archaic human forms. However, different consequences would be expected if only mild founder effects occurred when anatomically modern humans moved out of Africa. Under these conditions, gene trees would have a strong random component, and a certain fraction thereof, even in the absence of selection, would show two highly divergent major lineages [39]. The likelihood of finding gene genealogies with a very old common ancestor and very differentiated lineages would be even higher if the source African population was subdivided and structured genetically before dispersal, which is what most studies clearly suggest [40]–[43]. These theoretical considerations are actually matched by consistent results in simulation studies [5], [34], [44] and by variation in neurocranial geometry, suggesting significant levels of geographic structure among early modern humans from Africa [6].

One more piece of evidence in favor of the idea that seemingly archaic DNA in modern Eurasians is not due to the more fashionable "Neandertal introgression" but to ancient African population structure.

PLoS ONE 10.1371/journal.pone.0010648

The Microcephalin Ancestral Allele in a Neanderthal Individual

Martina Lari et al.

Background
The high frequency (around 0.70 worlwide) and the relatively young age (between 14,000 and 62,000 years) of a derived group of haplotypes, haplogroup D, at the microcephalin (MCPH1) locus led to the proposal that haplogroup D originated in a human lineage that separated from modern humans >1 million years ago, evolved under strong positive selection, and passed into the human gene pool by an episode of admixture circa 37,000 years ago. The geographic distribution of haplogroup D, with marked differences between Africa and Eurasia, suggested that the archaic human form admixing with anatomically modern humans might have been Neanderthal.

Methodology/Principal Findings
Here we report the first PCR amplification and high- throughput sequencing of nuclear DNA at the microcephalin (MCPH1) locus from Neanderthal individual from Mezzena Rockshelter (Monti Lessini, Italy). We show that a well-preserved Neanderthal fossil dated at approximately 50,000 years B.P., was homozygous for the ancestral, non-D, allele. The high yield of Neanderthal mtDNA sequences of the studied specimen, the pattern of nucleotide misincorporation among sequences consistent with post-mortem DNA damage and an accurate control of the MCPH1 alleles in all personnel that manipulated the sample, make it extremely unlikely that this result might reflect modern DNA contamination.

Conclusions/Significance
The MCPH1 genotype of the Monti Lessini (MLS) Neanderthal does not prove that there was no interbreeding between anatomically archaic and modern humans in Europe, but certainly shows that speculations on a possible Neanderthal origin of what is now the most common MCPH1 haplogroup are not supported by empirical evidence from ancient DNA.

Link

Allele surfing vs. Positive Selection

Continental human populations have very high allele frequency differences in several loci. One explanation for this phenomenon is that after their arrival in new lands, humans underwent selection for alleles that were appropriate in the new environments. An alternative explanation is that the frequencies were due to allele surfing, a process in which a small subset of individuals at the frontier of the expansion expands and multiplies into previously unsettled territory, causing their particular alleles to increase in frequency there.

From the paper:

The survey of the HGDP database on human polymorphisms reveals that large allele frequency differences between continental regions are extremely common. Indeed as much as 30% of loci show very large allele frequency differences between continents. These differences are unlikely to have been created by positive selection, but are more likely the result of neutral demographic processes such as the surfing phenomenon. Because the erosion of large allele frequency differences by mutation is slow, even for large mutation rates, the surprisingly large number of strongly differentiated STR alleles also do not need to be explained by the action of positive selection. Africa and the Americas show a much larger extent of differentiation than Eurasia or East Asia, which is certainly due to changes in allele frequencies during the colonisation of the Eurasian and the American continents. Disentangling the effects of selection and neutral demographic processes on genome diversity remains an important challenge of future human evolution studies.

This is a serious challenge to the selectionist paradigm and should be answered by its proponents. I would say that, from now on, the "gold standard" of positive selection should be concrete evidence that the proposed selected alleles actually do something that could have been selected, e.g., lactase persistence, where allele frequency differences are combined with a specific trait, which in turn is correlated with a particular selective influence (milk consumption after weaning). Statistical inference of selection without a comprehensive explanation is no longer intellectually convincing.

For example, ASPM and MCPH1 are loci that generated a lot of excitement as selection targets due to their large inter-group frequency differences. However, followup work has not found any substantial associations between them and anything of value: Has ASPM been the target of recent selection?, ASPM, MCPH1, CDK5RAP and BRCA1 and general cognition, reading or language. Were they really selected, or did they ride the wave of human advance?

Annals of Human Genetics doi: 10.1111/j.1469-1809.2008.00489.x

Large Allele Frequency Differences between Human Continental Groups are more Likely to have Occurred by Drift During range Expansions than by Selection

T. Hofer et al.

Several studies have found strikingly different allele frequencies between continents. This has been mainly interpreted as being due to local adaptation. However, demographic factors can generate similar patterns. Namely, allelic surfing during a population range expansion may increase the frequency of alleles in newly colonised areas. In this study, we examined 772 STRs, 210 diallelic indels, and 2834 SNPs typed in 53 human populations worldwide under the HGDP-CEPH Diversity Panel to determine to which extent allele frequency differs among four regions (Africa, Eurasia, East Asia, and America). We find that large allele frequency differences between continents are surprisingly common, and that Africa and America show the largest number of loci with extreme frequency differences. Moreover, more STR alleles have increased rather than decreased in frequency outside Africa, as expected under allelic surfing. Finally, there is no relationship between the extent of allele frequency differences and proximity to genes, as would be expected under selection. We therefore conclude that most of the observed large allele frequency differences between continents result from demography rather than from positive selection.

Link

Varki et al. (2008) on Human Uniqueness in Nature Reviews Genetics

From the paper:

Remarkable similarities of known human and chimpanzee protein sequences initially led to the suggestion that significant differences might be primarily in gene and protein expression, rather than protein structure6. Further analysis of alignable non-coding sequences affirmed this ~1% difference. However, the subsequent identification of non-alignable sequences that were due to small- and large-scale segmental deletions and duplications21–23 showed that the overall difference between the two genomes is actually ~4%.

...

Why are coding-sequence changes in brain genes under a larger degree of purifying selection than in other tissues? The reason for this is not immediately clear as a wide range of brain function supports life to reproductive age in humans.

...

But this notion, which is based on single nucleotide changes in protein-coding sequence, has to be reconciled with the CNV data, because CNVs in humans seem to be enriched among genes involved in neurodevelopmental processes.

...

However, connecting such genes involved in disorders of human cognition to the specific phenotypes undergoing selection poses significant challenges. A salient example involves two genes, abnormal spindle homologue microcephaly associated (ASPM) and microcephalin (MCPH1), the adaptive evolution of these genes in humans was claimed to be related to normal variation in brain size, on the basis of the fact that Mendelian mutations in each results in microcephaly in humans152,153. However, not all investigators have found evidence for the adaptive evolution of ASPM or MCPH1 (ref. 154). Also, neither gene is likely to contribute significantly
to normal variation in human brain size155. This case illustrates the challenges of interpreting genetic data in the face of complex phenotypes, especially those that are poorly understood.

Nature Reviews Genetics doi:10.1038/nrg2428

Human uniqueness: genome interactions with environment, behaviour and culture

Ajit Varki et al.

Abstract

What makes us human? Specialists in each discipline respond through the lens of their own expertise. In fact, 'anthropogeny' (explaining the origin of humans) requires a transdisciplinary approach that eschews such barriers. Here we take a genomic and genetic perspective towards molecular variation, explore systems analysis of gene expression and discuss an organ-systems approach. Rejecting any 'genes versus environment' dichotomy, we then consider genome interactions with environment, behaviour and culture, finally speculating that aspects of human uniqueness arose because of a primate evolutionary trend towards increasing and irreversible dependence on learned behaviours and culture — perhaps relaxing allowable thresholds for large-scale genomic diversity.

Link

ASPM, MCPH1, CDK5RAP and BRCA1 and general cognition, reading or language

See also:

• Microcephalin and ASPM do not Account for Brain Size Variability
• ASPM and the alphabet
• Has ASPM been the target of recent selection? (*)
• ASPM and Microcephalin don't make people smarter

It seems that about three years after the much publicized discovery of ASPM and MCPH1 variants thought to be under selection, the reason for their selection has yet to be discovered. Is this because these genes influence a human property that we can't measure or haven't thought of measuring, or is it perhaps that the supposed selection signatures are in fact not evidence of selection as an early skeptic (*) suggested?

Intelligence doi:10.1016/j.intell.2008.04.001

Recently-derived variants of brain-size genes ASPM, MCPH1, CDK5RAP and BRCA1 not associated with general cognition, reading or language

Timothy C. Bates et al.

Abstract

Derived changes in genes associated with primary microcephaly (MCPH) have been suggested to be “currently sweeping to fixation” i.e., increasing in frequency in most populations, with the likely outcome that the derived allele will completely displace the ancestral allele over time. Possible causes for this sweep include effects on human reasoning and language. Here we test the hypothesis that these derived alleles are associated with current variation in spoken or written language and related traits. The association of derived alleles of the ASPM, MCPH1, CDK5RAP2 and BRCA1 genes was tested against well-validated measures of dyslexia, specific language impairment, working memory, IQ, and head-size in a family-based association study of over 1776 subjects from 789 families of twins. No evidence for association was found for any gene to any trait. The results strongly did not support the hypothesis that derived alleles in MCPH-related genes are related to the evolution of human language or cognition. Results were compatible with the alternate hypothesis, suggesting that adaptations in these genes associated with a dramatic increase in brain size have long since reached fixation and are now maintained by stabilizing selection.

Link

Microcephalin haplotype from Neanderthals

Bruce Lahn continues his work on the Microcephalin haplogroup D. In a new paper in PNAS he and his team suggest that this brain gene may have introgressed into the modern human gene pool ~37kya from a separate Homo lineage, possibly the Neanderthals. Note that this is an open access article.

UPDATE (May 15, 2010): Neandertals had ancestral MCPH1 allele; hence this paper's inference is essentially falsified.

Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0606966103

Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage

Patrick D. Evans et al.

At the center of the debate on the emergence of modern humans and their spread throughout the globe is the question of whether archaic Homo lineages contributed to the modern human gene pool, and more importantly, whether such contributions impacted the evolutionary adaptation of our species. A major obstacle to answering this question is that low levels of admixture with archaic lineages are not expected to leave extensive traces in the modern human gene pool because of genetic drift. Loci that have undergone strong positive selection, however, offer a unique opportunity to identify low-level admixture with archaic lineages, provided that the introgressed archaic allele has risen to high frequency under positive selection. The gene microcephalin (MCPH1) regulates brain size during development and has experienced positive selection in the lineage leading to Homo sapiens. Within modern humans, a group of closely related haplotypes at this locus, known as haplogroup D, rose from a single copy {approx}37,000 years ago and swept to exceptionally high frequency ({approx}70% worldwide today) because of positive selection. Here, we examine the origin of haplogroup D. By using the interhaplogroup divergence test, we show that haplogroup D likely originated from a lineage separated from modern humans {approx}1.1 million years ago and introgressed into humans by {approx}37,000 years ago. This finding supports the possibility of admixture between modern humans and archaic Homo populations (Neanderthals being one possibility). Furthermore, it buttresses the important notion that, through such adminture, our species has benefited evolutionarily by gaining new advantageous alleles. The interhaplogroup divergence test developed here may be broadly applicable to the detection of introgression at other loci in the human genome or in genomes of other species.

Link

Microcephalin and ASPM do not Account for Brain Size Variability

Related to these recent papers, a new study on Microcephalin and ASPM, the "brain genes" under recent selection.

Human Molecular Genetics (Advance Access published online on May 10, 2006)

Normal Variants of Microcephalin and ASPM Do Not Account for Brain Size Variability

Roger P. Woods et al.

Abstract

Normal human brain volume is heritable. The genes responsible for variation in brain volume are not known. Microcephalin (MCPH1) and ASPM (abnormal spindle-like microcephaly associated) have been proposed as candidate genes since mutations in both genes are associated with microcephaly and common variants of each gene are apparently under strong positive selective pressure. In 120 normal subjects, we genotyped these variants and measured brain volumes using magnetic resonance imaging. We found no evidence that the selected alleles were associated with increases or decreases in brain volume. This result suggests that the selective pressure on these genes may be related to subtle neurobiological effects or to their expression outside the brain.

Link

Recent positive selection in humans

Yet another study on positive selection in modern humans; you can find many many more by searching for "recent selection" or "positive selection" via the site search on the right sidebar.

The findings are reported in PLoS Biology (free text). Nicholas Wade also covers the study in the New York Times:

Providing the strongest evidence yet that humans are still evolving, researchers have detected some 700 regions of the human genome where genes appear to have been reshaped by natural selection, a principal force of evolution, within the last 5,000 to 15,000 years.

The genes that show this evolutionary change include some responsible for the senses of taste and smell, digestion, bone structure, skin color and brain function.

Many of these instances of selection may reflect the pressures that came to bear as people abandoned their hunting and gathering way of life for settlement and agriculture, a transition well under way in Europe and East Asia some 5,000 years ago.

From the new paper:

A fully rigorous estimation of the ages of the candidate sweeps is difficult with the current data. However, making the simplistic assumption of a star-shaped genealogy for the favored haplotypes and assuming a generation time of 25 y, suggests average ages of ≍6,600 years and ≍10,800 years in the non-African, and African populations, respectively (Materials and Methods).

...

Some of the strongest signals of recent selection appear in various types of genes related to morphology. For example, four genes involved in skin pigmentation show clear evidence of selection in Europeans (OCA2, MYO5A, DTNBP1, TYRP1). All four genes are associated with Mendelian disorders that cause lighter pigmentation or albinism, and all are in different genomic locations, indicating the action of separate selective events. One of these genes, OCA2, is associated with the third longest haplotype on a high frequency SNP anywhere in the genome for Europeans. A fifth gene, SLC24A5, has recently been shown by another group to impact skin pigmentation and to have a derived, selected allele near fixation in Europeans [45]. Though iHS has reduced power for alleles near fixation, SNPs near this gene also show strong iHS signals in Europeans (Table S2).

Various genes involved in skeletal development have also been targets of recent selection. Three related proteins involved in bone morphogenesis show signals of selection in Europeans (BMP3 and BMPR2) and in East Asians (BMP5). In addition, GDF5, a gene in which mutations cause skeletal malformations, shows strong signals of selection in both Europeans and East Asians. Other morphological features also appear to be targets of selection, including hair formation and patterning in Yoruba (the keratin cluster near 17q12; and FZD6).

An important type of selective pressure that has confronted modern humans is the transition to novel food sources with the advent of agriculture and the colonization of new habitats [19,21]. As noted above, we see a strong signal of selection in the alcohol dehydrogenase (ADH) cluster in East Asians, including the third longest haplotype around a high frequency allele in East Asians. A variety of genes involved in carbohydrate metabolism have evidence for recent selection, including genes involved in metabolizing mannose (MAN2A1 in Yoruba and East Asians), sucrose (SI in East Asians), and lactose (LCT in Europeans). Processing of dietary fatty acids is another system with signals of strong selection, including uptake (SLC27A4 and PPARD in Europeans), oxidation (SLC25A20 in East Asians) and regulation (NCOA1 in Yoruba and LEPR in East Asians). The latter gene (LEPR) is the leptin receptor and plays an important role in regulating adipose tissue mass.

Recent articles have proposed that genes involved in brain development and function may have been important targets of selection in recent human evolution [8,9]. While we do not find evidence for selection in the two genes reported in those studies (MCPH1 and ASPM), we do find signals in two other microcephaly genes, namely, CDK5RAP2 in Yoruba, and CENPJ in Europeans and East Asians [46]. Though there is not an overall enrichment for neurological genes in our gene ontology analysis, several other important brain genes also have signals of selection, including the primary inhibitory neurotransmitter GABRA4, an Alzheimer's susceptibility gene PSEN1, and SYT1 in Yoruba; the serotonin transporter SLC6A4 in Europeans and East Asians; and the dystrophin binding gene SNTG1 in all populations.

PLoS Biology Volume 4 | Issue 3 | MARCH 2006

A Map of Recent Positive Selection in the Human Genome

Benjamin F. Voight1, Sridhar Kudaravalli1, Xiaoquan Wen1, Jonathan K. Pritchard1*

The identification of signals of very recent positive selection provides information about the adaptation of modern humans to local conditions. We report here on a genome-wide scan for signals of very recent positive selection in favor of variants that have not yet reached fixation. We describe a new analytical method for scanning single nucleotide polymorphism (SNP) data for signals of recent selection, and apply this to data from the International HapMap Project. In all three continental groups we find widespread signals of recent positive selection. Most signals are region-specific, though a significant excess are shared across groups. Contrary to some earlier low resolution studies that suggested a paucity of recent selection in sub-Saharan Africans, we find that by some measures our strongest signals of selection are from the Yoruba population. Finally, since these signals indicate the existence of genetic variants that have substantially different fitnesses, they must indicate loci that are the source of significant phenotypic variation. Though the relevant phenotypes are generally not known, such loci should be of particular interest in mapping studies of complex traits. For this purpose we have developed a set of SNPs that can be used to tag the strongest ∼250 signals of recent selection in each population.

Link

Stop the presses... huge papers on brain evolution in recent humans

I am very sure that a set of new papers (one two) in Science will generate a huge amount of buzz. I will blog in more detail about them later, but for now, this Red Nova story covers the findings pretty well. The interesting part:

The team also observed geographic differences. For haplogroup D of ASPM, they found that it occurs more frequently in Europeans and surrounding populations including, North Africans, Middle Easterners, and South Asians, and at a lower incidence in East Asians, New World Indians and sub-Saharan Africans. For microcephalin, the researchers found that haplogroup D is more abundant in populations outside of sub-Saharan Africa.

For now, from the papers:



Fig. 3. Global frequencies of Microcephalin haplogroup D chromosomes (defined as having the derived C allele at the G37995C diagnostic SNP) in a panel of 1184 individuals.



Fig. 1. Worldwide frequencies of ASPM haplogroup D chromosomes (defined as having the derived G allele at the A44871G diagnostic polymorphism), based on a panel of 1186 individuals.

UPDATE

Here is what these studies mean:

• Microcephalin and ASPM are genes involved in regulating brain size
• A variant of Microcephalin has reached very high frequencies in non-Sub-Saharan Africans in the last 37,000 years.
  
• A variant of ASPM has reached very high frequencies especially in Caucasoids but also in some southern Mongoloids and Australoids in the last 5,800 years.
  
• It is almost inconceivable that these two factors were caused by random factors (drift). Therefore selection has acted on these two genes, favoring the new Microcephalin variant in non-Sub-Saharan Africans and the ASPM especially in Caucasoids, but also to a lesser extent in some southern Mongoloid and Australoid groups.
• We know absolutely nothing about what the new Microcephalin and ASPM variants actually do. What we do know is that they confer some substantial advantage that has caused them to grow in numbers. Perhaps, they confer some cognitive or behavioral ability.
  

These are the facts. The interpretation of the facts must wait until we have more information. However, the dates for the expansion of the two variants are extremely suggestive.

In a recent article, Erik Trinkaus has surveyed the human paleoanthropological record, and wrote that:

The earliest candidates for human anatomical modernity, those between ca. 150,000 and 195,000 years B.P. in Africa, are best considered as bridging a morphological gap between late archaic and early modern humans.

...

The spread of modern humans thoughout Africa and into Eurasia occurred after 50,000 years B.P. and probably after 40,000 years B.P., 100,000 years after their appearance.

Now, it may be a coincidence that the spread of humans throughout Africa and into Eurasia happened at around the same time that the new Microcephalin variant appeared, but the timing is certainly suggestive.

The question is: why did the new variant not get selected in Sub-Saharan Africans? There are only two possible explanations:

• There is something in the Sub-Saharan African environment which did not allow the variant to be selected; in other words: the variant did not confer an advantage in Africa itself.
• The gene pool of most Sub-Saharan Africans did not possess the new Microcephalin variant. Hence the variant did not get selected because it was lacking in the Sub-Saharan African gene pool.
  

Now, it is well known that the greatest difference in modern human genetic variation is between Sub-Saharan Africans and non-Sub-Saharan Africans. This is the result of the fact that humans originated in Africa, and possess only a subset of the variation that exists there.

As I have written before, there is good reason to believe that a human group originated in eastern Africa ("Afrasians") and came to colonize the rest of the world in relatively recent times. But, the rest of the African continent was already inhabited by pre-existing anatomically modern humans ("Paleoafricans") since at least 150,000 years in the past. These "Paleoafricans" were separated from the "Afrasians", as evidenced by the fact that typical "Paleoafrican" markers, originating long before the 40,000BP cutoff date, such as Y-haplogroups A and B and mtDNA haplogroups L0-L2 are not found in Eurasia.

If my theory is correct, then we don't need to propose some unquantifiable peculiarity of the African environment. Rather, the new Microcephalin variant has a low frequency in Sub-Saharan Africans precisely because it emerged in the Afrasians of eastern Africa that started colonizing the world around 40,000BP and was later added to the Paleoafrican populations of Sub-Saharan Africa. It simply has not had enough time to spread in most of Africa!

The second variant (of ASPM) is even more impressive, because it started to spread only 5,800 years ago, although the confidence margins are wide. The only movement which could have affected so many populations of Eurasia, regardless of language, in the last few millennia is the Neolithic expansion, followed by population growth in the first civilizations of the Near East and China.

It seems all by certain that the variant first appeared in Western Eurasia. It could have been carried easily to the east by the Near Eastern Neolithic people who reached India. It would only take a small step to make the jump to the Mongoloid world; once introduced into the population, it would also undergo the same selection process that made it so frequent among Caucasoids. However, agriculture begins much later among Mongoloids and even later among Australoids. So, the low frequency of the new variant in these populations is a consequence of the fact that it has had less time to spread among these populations.

The new ASPM variant is lacking in Sub-Saharan Africans and Native Americans. These results can be easily explained:

• Sub-Saharan African agriculture is late, and moreover there has been almost no gene flow from Eurasia into Sub-Saharan Africa, with a few occasional exceptions. So, the ASPM variant did not exist in the Sub-Saharan African gene pool, and could thus have not been selected.
• Native Americans migrated into the New World in Paleolithic times. Naturally, the ASPM variant was not present in their ancestral gene pool yet, so it could not have been selected.

The importance of these new papers is that cognitive evolution in Homo sapiens did not stop after our lineage became anatomically modern, and it did not stop when a subet of anatomically modern humans set out to colonize the world 40,000 years ago from eastern Africa, and it did not stop when Neolithic man appeared 10,000 years ago. Evolution has continued, and the proof for it is in the genetic variation of living human populations.

Science, Vol. 309 No. 5741

Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans

Patrick D. Evans et al.

The gene Microcephalin (MCPH1) regulates brain size and has evolved under strong positive selection in the human evolutionary lineage. We show that one genetic variant of Microcephalin in modern humans, which arose ~37,000 years ago, increased in frequency too rapidly to be compatible with neutral drift. This indicates that it has spread under strong positive selection, although the exact nature of the selection is unknown. The finding that an important brain gene has continued to evolve adaptively in anatomically modern humans suggests the ongoing evolutionary plasticity of the human brain. It also makes Microcephalin an attractive candidate locus for studying the genetics of human variation in brain-related phenotypes.

Link

Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens

Nitzan Mekel-Bobrov et al.

The gene ASPM (abnormal spindle-like microcephaly associated) is a specific regulator of brain size, and its evolution in the lineage leading to Homo sapiens was driven by strong positive selection. Here, we show that one genetic variant of ASPM in humans arose merely about 5800 years ago and has since swept to high frequency under strong positive selection. These findings, especially the remarkably young age of the positively selected variant, suggest that the human brain is still undergoing rapid adaptive evolution.

Link