Author : Wahid Ahmad
What makes us truly human?
Is it our upright, hairless bodies or our highly organized brains, our
sophisticated culture, or our ability to articulate complex ideas through
precise symbols? Fascinatingly, we share many of these remarkable traits with Neanderthals,
our closest and most intriguing evolutionary cousins. Yet, many anthropologists
argue that Neanderthals are a distinct species, pointing to unique physical
characteristics. While modern humans have a rounded braincase, a small divided
brow ridge, and a narrow pelvis, Neanderthals display a longer skull, a
prominent continuous brow ridge, and wider hipbones. These differences are significant
to categorise Neanderthals and modern humans as separate species. Genetic data
indicates that our lineages diverged over 500,000 years ago, though we
occasionally interbred, leaving a fascinating legacy in our shared history.
Until a few years ago,
scientists thought that while Homo sapiens started spreading out from Africa at
least 60,000 years ago, they didn't reach Europe until much later, around
41,000 years ago. This delay was believed to be due to the need for adaptations
to Europe's colder climate or because Neanderthals successfully kept modern
humans out for many millennia.
However, recent research has
shown that early Homo sapiens and late Neanderthals likely coexisted in Europe
for a longer period than previously thought. Additionally, DNA evidence reveals
that these two groups interbred multiple times both in Europe and Asia.
Modern human genetic diversity patterns have
been shaped by past demographic events and interactions. As humans migrated out
of Africa, a series of events like geographic isolations, population
replacement, gene flow and selective pressures created a gradient of genetic
diversity, with populations farther from Africa genetically less diverse.
Recent research highlights that modern humans
also carry genetic legacies from admixture with archaic humans, including
Neanderthals and Denisovans. Neanderthal ancestry is found in Eurasia, Oceania,
the Americas, and North Africa, while Denisovan ancestry is mainly in Asia, the
Americas, and Oceania. Additional archaic ancestry has been identified in
African populations. Archaic ancestry levels vary with about 1% in Africans, 2%
in Eurasians, and up to 6% in Oceania.
Neanderthals evolved in Europe for at least
400,000 years. In the Atapuerca hills of northern Spain, the Sima de los Huesos
cave contains many early human skeletons dating from about 430,000 years ago.
These bones were identified as early Neanderthals, a conclusion supported by
ancient DNA analysis.
Genetic data from these fossils and later
Neanderthals suggest that Neanderthals and modern humans began to diverge about
600,000 years ago. This challenges previous beliefs about the last common
ancestor of Neanderthals and Homo sapiens, which was thought to be Homo
heidelbergensis or rhodesiensis. Fossils of this species are found in Europe
and Africa and were believed to have started splitting into Neanderthals and
modern humans about 500,000 years ago.
However, new dating of the Kabwe cranium
belonging to Homo rhodesiensis indicates it is only about 300,000 years old,
much younger than expected. Additionally, studies show that rhodesiensis had a
facial structure less likely to be ancestral to modern humans. Therefore, there
isn't enough evidence to determine the exact nature or location of our last
common ancestor with Neanderthals from around 600,000 years ago.
If our evolution goes back about 600,000
years, where are the early fossils of our species? Until recently, scientists
thought the oldest Homo sapiens fossils were from Ethiopia, dating back 150,000
to 200,000 years. These fossils named Omo Kibish and Herto, have features typical of modern
humans. However, there is a large time gap between these fossils and our
ancient common ancestor with Neanderthals.
In 2017, fossils from Jebel Irhoud in
Morocco, dating back 300,000 years, suggested early members of the Homo sapiens
lineage. These fossils have a mix of ancestral and more modern features, along
with evidence of complex behaviors like controlled use of fire and advanced
stone tools.
At around 300,000 years ago, there were other
human species in Africa like Homo naledi in South Africa.
Pan-African model of human origin is now
widely accepted, as early Homo sapiens were diverse and widely spread across
Africa. Changing climates caused different populations to evolve, merge, or
disappear over hundreds of thousands of years, eventually leading to modern
humans.
About 60,000 years ago, Homo sapiens began to
spread from Africa, with Neanderthals disappearing in the following 20,000
years of the dispersal. New discoveries show that these two events may be
connected, revealing interactions and interbreeding between the species 40,000
to 60,000 years ago.
Although Neanderthals and Homo sapiens
evolved mainly in separate regions, they exchanged some genes about some 250,000
years ago, possibly due to brief migrations of early Homo sapiens into Eurasia.
Evidence of this contact includes shared technology and fossils like those
found in Apidima Cave from Greece. One sapiens-like braincase from this site is
dated to at least 210,000 years ago.
This fossil called Apidima 1 has features
typical of Homo sapiens, such as a high and rounded braincase, suggesting an
early population of Homo sapiens in Greece by 210,000 years ago. This group was
likely related to similar populations in the Levant and was later replaced by
Neanderthals around 170,000 years ago.
If the Apidima analyses are correct, Homo
sapiens entered Europe over 150,000 years earlier than previously thought. The
most likely route from Africa was through the Levant and Turkey. Evidence of
early DNA exchanges between Neanderthals and Homo sapiens supports this theory.
There are signs of other early excursions of
Homo sapiens from Africa, such as fossils in Israel at sites like Skhul,
Qafzeh, and Misliya dating over 100,000 years ago. These remains show that
later Homo sapiens were present in the region between 100,000 to 130,000 years
ago.
Recent finds at Nesher Ramla in Israel
suggest there was significant human variation in the region, possibly including
co-existence of Homo sapiens and Homo neanderthalensis.
Interbreeding with archaic humans introduced
new genetic variants into modern humans. Over time selective forces shaped
these archaic genome segments, influencing their current distribution among
modern humans.
Neanderthal DNA makes up about 2% of the
genomes of all non-African populations today. Different individuals carry different
Neanderthal variants, and these variants can vary significantly in frequency
among populations. A smaller number of Neanderthal-derived variants are also
found in sub-Saharan Africa due to gene flow from Europe and Western Asia after
the Neanderthals disappeared.
The consistent 2% Neanderthal DNA in
present-day genomes suggests that most Neanderthal contributions occurred about
60,000 years ago when populations left Africa and became ancestors to all
non-Africans. However, some Neanderthals also contributed locally to early
European modern human groups, such as a 40,000-year-old individual from Romania
and three 45,000-year-old individuals from Bulgaria. These early populations
did not leave many descendants that contributed genetic variants to present-day
populations, so their impact was limited.
The genetic changes that accumulated on
archaic and modern human lineages impacted the physiology of Neanderthals,
Denisovans, and modern humans, with the first two becoming extinct.
When modern humans interbred with
Neanderthals, their offspring had one set of modern human chromosomes and one
set of archaic chromosomes. Over 2,000 generations, these archaic DNA segments
became shorter due to recombination, resulting in scattered fragments in
today's genomes.
Typically, an archaic DNA segment today is
about 50 kilobases long. However, the actual lengths vary, reflecting past
recombination events. For a fragment to be confidently identified as archaic
and from about 2,000 generations ago, it must be of substantial length.
Some DNA segments in humans are similar to
Neanderthal or Denisovan DNA not because of recent gene flow, but because these
segments have persisted since the common ancestor of modern and archaic humans.
These segments are usually shorter than 12 kb due to longer recombination
periods.
The size of archaic DNA fragments also
depends on local recombination rates, which vary across the genome, among
populations, and over time.
A typical 50 kb segment of Neanderthal DNA
will carry about 16 unique variants from mutations that occurred on the
Neanderthal lineage. Modern humans have accumulated a similar number of unique
variants independently. Thus, archaic DNA segments often stand out because they
carry more single nucleotide variants than surrounding regions.
The way Neanderthal segments are spread
across modern human genomes suggests interbreeding occurred between 50,000 and
60,000 years ago, before East Asians and Europeans split into distinct groups.
The genome of an ancient individual called
Ust’-Ishim, who is equally related to modern East Asians and Europeans, has
similar levels of Neanderthal DNA as present-day Eurasians. This supports a
single episode of interbreeding around 52,000–58,000 years ago.
Several ideas try to explain why East Asians
have more Neanderthal DNA. It could be due to stronger natural selection in
Europe reducing Neanderthal DNA over time, or because a population without
Neanderthal genes mixed with Europeans later on. Another possibility is that
interbreeding happened multiple times: initially into the ancestors of both
East Asians and Europeans, followed by additional mixing with East Asians after
the populations had diverged.
Scientists analysed Neanderthal DNA fragments
in modern human genomes, found that East Asians have more Neanderthal ancestry compared
to Europeans with arround 19.6% enrichment in East Asians.
By studying Neanderthal DNA fragments in
Europeans and East Asians, strong evidence supporting multiple episodes of
interbreeding between Neanderthals and humans.
After an initial mixture when humans first
entered Eurasia, there were subsequent pulses of Neanderthal DNA introgression
into both European and East Asian populations. This on-going mixing likely
contributed to the higher level of Neanderthal ancestry observed in East Asians
compared to Europeans.
These findings contrast with theories
proposing that differences in Neanderthal ancestry between Europe and Asia are
solely due to dilution in Europe from a population called basal Eurasians, who
lacked Neanderthal ancestry. While dilution may have played a role, results
indicate that multiple admixture events were crucial in shaping Neanderthal DNA
patterns across Eurasia.
Neandertal genes in modern humans can affect how our bodies process food
and drugs. For instance, some Neandertal DNA on chromosome 17 alters how a
liver protein handles fats and sugars, making people more prone to type 2
diabetes. Other Neandertal genes increase the risk of protein and calorie
deficiencies and can affect how medications are metabolized in the body.
Neandertal genes affect how we feel pain and handle pregnancies today.
On chromosome 2, a piece of Neandertal DNA changes a protein (SCN9A) that
controls how sensitive we are to pain. Neandertals had versions of this protein
that made them more sensitive to pain. Today, about 0.4% of people in the UK
carry this Neandertal version and say they feel more pain than others. This
sensitivity might have helped Neandertals avoid danger.
On chromosome 11, another piece of Neandertal DNA affects the
progesterone receptor, important for pregnancy. This gene variant is linked to
a higher risk of premature in modern humans. But it also seems to protect
against bleeding and miscarriages early in pregnancy. This trade-off suggests
that these genetic differences from Neandertals have influenced our health
today, showing how ancient genes still play a role in our lives. Notably, two
different versions of the Neandertal progesterone receptor gene have been
contributed to modern humans, and both have risen in frequency, as shown by an
increase in their occurrence in skeletal remains of individuals over the past
10,000 years. Both Neandertal versions result in a higher progesterone effect
during pregnancies. This is compatible with the finding that progesterone
administration lowers miscarriage rates in women who previously experienced
miscarriages.
Archaic humans like Neandertals left genetic marks in our immune systems
that still affect us today. They had gene variants that helped them fight
infections, likely because diseases were a big threat back then. Some of these
Neandertal genes are still with us and influence how our immune systems respond
to infections.
For example, on chromosome 4, there's a DNA segment from Neandertals
that boosts our immune response by increasing the expression of receptors on
cells that recognize and fight microbes. This likely helped Neandertals resist
certain infections, like Helicobacter pylori. Today, these genetic variants are
found in different frequencies across human populations, which suggests they
were influenced by local diseases over time.
Another Neandertal DNA segment on chromosome 3 affects our risk from
severe infections like SARS-CoV-2. People with this segment have a higher risk
of needing mechanical ventilation or dying from such infections. However, this
segment also reduces the risk of getting infected with HIV, possibly by
affecting the expression of a gene called CCR5.
These genetic differences show how ancient humans adapted to their
environments, including the diseases they faced. It's similar to how modern
humans adapted to diseases like malaria, which shaped the prevalence of traits
like sickle cell anemia. Studying these Neandertal genes gives us insights into
our evolutionary history and why our immune systems vary across different
populations today.
Complex traits in humans, like height or cognitive abilities, are
influenced by many genetic variants scattered across the genome, as well as
environmental factors. Understanding how genes from archaic humans affect such
traits is challenging because each genetic change typically has a small effect.
Researchers don't directly link individual archaic variants to specific
traits like height or intelligence. Instead, they analyze whether the
collective presence of Neandertal or Denisovan genes in a population tends to
influence traits in a certain direction or contributes to the variability in
the risk of complex diseases.
For instance, studies have found that Neandertal DNA contributes
significantly to variations in the risk of conditions like depression and
sun-induced skin lesions. However, when looking across a wide range of traits,
it's been observed that archaic genes have less impact than initially expected.
Among 405 complex traits studied, dermatological traits showed the most
influence from Neandertal ancestry, while cognitive traits were least affected.
This aligns with the understanding that Neandertal genetic influence is less
pronounced in brain-related genes compared to genes influencing other parts of
the body.
Gene expression levels play a crucial role in influencing many complex
traits. Studies have shown that Neandertal genetic variants tend to be
expressed at lower levels compared to modern human variants in individuals who
carry both types of genes. This difference is particularly noticeable in
tissues like the testis and parts of the brain such as the cerebellum and basal
ganglia. It suggests that there has been strong evolutionary pressure against
Neandertal regulatory sequences in these specific tissues, which aligns with
the limited impact of Neandertal genes on cognitive traits.
Archaic variants that are older seem to have been more tolerated among
modern humans compared to more recent ones. Variants shared between different
Neandertal individuals or between Neandertals and Denisovans are likely older.
In terms of gene regulation, older archaic variants that increase gene
expression are less common in present-day populations, except for those shared
between Neandertals and Denisovans. This suggests that variants persisting in
archaic groups for longer periods might have had less harmful effects on modern
humans, possibly because they were better adapted to ancestral conditions or
underwent more rigorous selection processes over time.
Denisovans are less studied due to the limited availability of
high-quality genomes. However, one significant Denisovan genetic contribution
is a 33-kb DNA segment on chromosome 2 found in over 80% of Tibetans but rare
in other Asian populations. This segment contains the EPAS1 gene, which helps
in adapting to low oxygen levels at high altitudes. Denisovans likely adapted
to life on the Tibetan plateau and passed on this genetic advantage to modern
humans who migrated to the region.
Genetic variants inherited from Neandertals affect how genes are turned
on and off in modern humans. Studies show that Neandertal variants tend to be
expressed less than modern human variants, especially in tissues like the brain
and testis. Older Neandertal variants are better tolerated in modern
populations, possibly because they had more time to undergo natural selection.
Newer variants may have more detrimental effects since they haven't been
refined through evolution as much. These insights help explain how Neandertal
genes influence traits and diseases in present-day humans.
Ancestral genetic variants that were once thought absent in present-day
humans are now being discovered in diverse populations worldwide. These
variants either persisted since the common ancestors of modern and archaic
humans around 600,000 years ago, especially prevalent in African populations
with high genetic diversity, or were introduced by interbreeding with
Neandertals and Denisovans. Populations like those in Oceania, with higher
levels of archaic ancestry, show particularly elevated levels of reintroduced
ancestral variants. As genomic studies expand to include more diverse
populations, more of these ancient genetic variants, previously considered
lost, are likely to be uncovered. This broader data will enhance our
understanding of how these variants influence human traits and health.
The presence of rare ancestral genetic variants in modern humans
challenges how we define modernity genetically. Paleoanthropologists define
Neandertals based on skeletal features like robustness, prominent brow ridges,
and certain skull shapes, most of which are distinctive to Neandertals.
However, some modern humans exhibit similar skeletal traits. Yet, only
Neandertals possess a combination of all or most of these features.
Similarly, modern human genetics can be understood as a mix of derived
genetic features, not universally present in all individuals today. Some modern
traits exist in their ancestral forms in certain people due to persistence from
common ancestors with archaic humans or through interbreeding with Neandertals
and Denisovans. Conversely, some modern genetic traits are found in late
archaic humans, showing they were introduced from modern humans.
Certain modern human traits are nearly fixed across all populations,
such as specific genetic changes that are absent in Neandertals and Denisovans.
Studying these unique genomic regions can provide insights into what makes
modern humans distinct genetically.
The genomes of Neandertals and Denisovans reveal they shared common
ancestors with modern humans around 600,000 years ago, while the ancestor of
all present-day humans existed about 300,000 years ago. Only a small fraction
of the genome, about 1.5% to 7%, differs significantly between modern and
archaic humans. These regions contain genetic variants where frequencies vary
greatly between the two groups, influencing the modern human phenotype.
From a genetic standpoint, modern humans are defined by a combination of
genetic features, where each person carries most but not necessarily all of
these traits. This "combinatorial view" acknowledges that some
genetic changes may have had more significant functional impacts than others.
The emergence of these changes likely occurred in a population ancestral to modern
humans, setting them apart from other contemporaneous human forms.
Studying gene flow between archaic and modern humans helps us understand
the physiological effects of these genetic variants. Archaic variants
introduced into modern human populations through interbreeding are often rare,
making them challenging to study. Increasing diversity in biobanks, with
participants from various ancestries, will be crucial for studying these rare
variants, as they may have reached higher frequencies in smaller, isolated populations.
It's essential to recognize that ancestral variants associated with
developmental or adult effects are not inherently "primitive" or
"pathological." These variants functioned effectively in healthy
archaic humans for hundreds of thousands of years, closely related to modern
humans, and likely continue to function well in people today.