Mulitcellular Organisms

What Makes Us Human?

The question of "What makes us human?" has been pondered by philosophers and others since time immemorial. The answer is usually implied in the charateristics of humans. We can draw up a list of differences: bodily differences such as the plantigrade (flat to the floor) foot, opposable thumbs, bipedal gait and big brains; mental differences in intelligence, speech, imagination, tool manufacture and use, fire and cooking; and social differences in culture, religion, music, art, reason, use of

Figure 10-34a Human and other Primates [view large image]

medicine, social learning and the formation of social groups. Such list would separate us more or less from the other animals (Figure 10-34a). Table 10-05 lists some different characteristics between human and other species.

Characteristics	Other Species	Human	Function(s)
Cooperation	Few	Common in human societies	Better chance of success in difficult tasks
Science	No	Involving abstract concept	Study of the material world
Etiquette	Unknown	Manners in social contact	Keep microbes away from each other to show good will
Play	Limited	Devoting lot of time and involving many friends	Learning and social development
Rules	Pecking Order	Set of rules for members in a society	Maintenance of stable society
Monogamousness	< 10%	Most common mating arrangement	Reduce efforts in keeping the dominant position
Intercourse	Open copulation	In privacy	Hiding infidelity
Gossip	Grooming	Grooming with language	Maintenance of personal relationship

Table 10-05 Different Characteristics between Human and Other Species

Figure 10-34b shows the steps leading to human starting from 6 million years ago with the split of the chimp and human lineages.

Figure 10-34b Becoming Human [view large image]

Figure 10-34c is a pictorial portray of the human evolution in various body parts (edited from an image in the September 2014 issue of "Scientific American"). The dates are color coded as shown in right edge of the image. It is apparent that most of the changes in walking gait occurred earlier between 4 - 2 million years ago (mya) in the lower limbs; while the changes in the upper limbs for "tool use" happened from 3 - 1 mya. The exception is in the opening of the spinal cord under the skull, it had been moved forward much earlier at 7 mya. Figure 10-34d depicts the evolution of locomotion, tool use, and brain size. It shows the first tool use and striding gait occurred in about the same time at 2 mya. The brain size was doubled with the emergence of more sophisticated tools at about 1 mya. There was another doubling in brain size when fire, clothing, ... were invented by Homo Sapiens about 500,000 mya.


Figure 10-34c Becoming Human in Picture [view large image]	Figure 10-34d Evolution of Locomotion, Tool Use, and Brain Size [view large image]

Genetically, recent study in 2004 by comparing the sequence of chimpanzee chromo-some 22 with the equivalent human chromosome 21 reveals that 1.5% of the former consists of single-base substitutions, in addition to nearly 68000 insertions or deletions. That's sufficient to generate changes in most proteins and appearance. Table 10-06 lists a few of the known mutations in human genes and the consequence.

Gene	Mutation in Human	Function
AMY1	More copies	Digestion of starch
ASPM	Several bursts of change	Brain size
DARC	Single point mutation on "Duffy Antigen Receptor"	Suppress expression of DUFFY to block malaria infection
DUF1220	Lot of duplicated copies	High cognitive function
EDAR	EDAR Single nucleotide polymorphism (SNP)	Straight black hair
FOXP2	In 2 locations of the amino-acid sequence	Speech and Language
HAR1	Substantial change	Fetal brain tissue development
HAR2	Second most changes (after HAR1)	Wrist and thumb development
LCT	Mutation on chromosome 2	Digestion of milk sugar in adulthood
MYH16	Tiny mutation	Affecting jaw muscle leading to smaller jaw
SLC24A5	Different versions in exons of the SLC24A5 gene	Difference in skin colour
TRIM5	Single base change	For combating the PtERV1 virus

Table 10-06 Gene Mutations in Human

The small difference in genes suggests that it also depend on molecular switches that tell genes when and where to turn on and off. These molecular switches lie in the noncoding regions of the genome once known as junk DNA. Much of the genome's junk DNA is the residue of evolutionary events long forgotten and no longer relevant. But a subset of them known as functional noncoding DNA, comprising <

some 3% to 4% of the genome and mostly embedded within and around the genes, is crucial. It seems to govern a lot of what we actually see. A new study has found the strongest evidence yet in the brain's right prefrontal cortex that sets humans apart from other primates. This is the site where we understand the mental processes of others - the basis of our socialization and what makes us human. It gives rise to our capacity to feel empathy, sympathy, understand humor and when others are being ironic, sarcastic or even deceptive. It is the cumulative result of 300,000 years of tool-making evolution, which requires the ordering of sequences and the hierarchical assembly of the same components into different configurations (to make tools of different functions). As makers of single-component tools, we progressed at a remarkably slow pace starting about 2.5 million years ago. But with the appearance of composite tools, near-modern brain size anatomy and perhaps of grammatical language 300,000 years ago, the pace quickened exponentially.

Figure 10-35a Human-like Consciousness in Other Animals [view large image]

We became long-range planners and grammatical speakers. Eventually, we possess all the prefrontal capacities - working memory, our sense of self, and theorizing about other people's minds. The so-called intentionality now constitutes the essential ingredient for the new definition of humans. However, it is still not completely distinctive. Human children cannot distinguish between their own intentions and those

of others until the age of four. Such ability develops gradually over the years, continuing well into adolescence. It is known that some parts of the brain are still developing in that age. They are responsible for many problems associated with teenagers' unique behavioural traits. Figure 10-35a shows some elements of the supposedly unique human-like consciousness shared by other animals.

With the publication of the draft DNA sequence of the chimpanzee genome in the summer of 2005, more data are now available for understanding human biology and evolution. Although the human and chimpanzee genomes are very similar, there are about 35 million nucleotide differences, 5 million indels (insertions or deletions) and many chromosomal rearrangements to take into account. Most of these changes will have no significant biological effect, so identification of the genomic differences underlying such characteristics of "humanness" as large cranial capacity, bipedalism and advanced brain development remains a very difficult task. Given the short time since the human-chimpanzee split, it is likely that a few mutations of large effect are responsible for part of the current physical (phenotypic) differences that separate humans from chimpanzees and other great apes.

Figure 10-35b Gene Evolution

Protein evolution - Natural selection is commonly thought to operate mainly at the protein level. For this reason, nucleotide changes in protein-coding regions are usually classified into two groups: "synonymous changes" K_S (which do not cause any change in amino-acid) and "non-synonymous changes" K_A (which do cause amino-acid changes). It is found that protein-coding regions with K_A/K_S > 1 (which means a lot of non-synonymous changes) are not involved in processes related to supposed humanness traits. They are mostly related to host-pathogen interaction, immunity and reproduction. Such pattern is also found in rats, mice and other mammals. However, some regions with small K_A/K_S may actually have produced dramatic consequence. For example, two amino-acid changes alone in the highly conserved FOXP2 protein (a gene-transcription factor) might have contributed to the human capacity for speech.
Less -is-more - This hypothesis posits that loss-of-function changes relative to the "prototypical ape" traits are characteristic of certain humanness traits - for example, lack of body hair, preservation of some juvenile traits into adulthood and expansion of the cranium. Such loss-of-function changes could be caused by non-synonymous substitutions, indels, loss of coding regions and deletions of entire genes. The comparisons to the chimpanzee have unveiled 53 human genes with disruptive indels in the coding regions, and genes in this category may be associated with intriguing phenotypes. Small indels could plausibly be major contributors to human-chimpanzee phenotypic differences, especially given that these mutations can also influence the two other hypotheses for the evolution of humanness (see triple overlapped area at the center of Figure 10-35b).
Gene-regulatory evolution - There is a long-standing hypothesis that the phenotypic differences between humans and chimpanzees primarily arise from changes in gene-regulatory regions - the promoter regions. The current analyses do not address this issue in detail, because it is still notoriously difficult to identify such regions. This hypothesis is the hardest to test, yet it may be the most promising one.

Figure 10-35b depicts each of the three hypotheses by a circle, with note of the mechanisms or processes that could underlie the evolutionary change. A missense mutation causes an amino-acid change; a nonsense mutation causes a sense codon to change into a stop codon, resulting in premature termination of DNA transcription; and exons are coding sequences.

It is found that one gene contains a protein-coding domain that is repeated 212 times in people, compared with 37 repeats in chimps, 30 in macaques and one in mice and rats. This protein domain is active in human brain cells and other tissues. Genomic study of the patients with brain dysfunctions found that of the 290 cases with unexplained mental retardation, one patient had a deletion in the same region of the relevant gene.
Mutating the relevant genes in mice indicates that they could enlarge mouse brains by inducing fetal mice to over-express the regulatory chemical -catenin. That suggested the chemical might regulate pathways that control human brain size.
By comparing the human and chimp genomes, one gene is found to evolve rapidly during the transition from chimps to people. This gene is expressed at 7 - 19 weeks of human fetal development, when neurons are know to be forming and moving throughout the brain.

There are many riddles during the course of human evolution, Table 10-07 below lists a few of them together with the estimated time period (in MYA - Million Years Ago) or first appearance (FA), and tentative explanation(s).

Time (MYA)	Riddle	Tentative Explanation(s)
6 (last common ancestor)	There's only 1% difference between the genomes of humans and chimps	Difference in gene expressions with culture feed back loop (to be discovered)
~ 4.2 (FA), 1.7 (descending to savannah)	Transition to bipedal requires anatomical changes and clumsy trial period	Package of advantages including freed hands to perform tasks, long distant traveling, ...
2.6 - 0.5	It took a long time for technological advance from stone flakes to hand axes	The development requires bigger brain and more complicated neural connections
~ 2	Evolution to a big brain, which consumes a lot of energy	Single mutation weakened the jaw muscles, which constrained the growth of the brain
1.6 - 0.6	It is not known exactly when did language evolve	The quoted time interval is between the appearance of neural connections in chest/diaphragm and change in voice box
~ 0.2	Humans shed hair which is so useful for insulation by all mammals	A possibility is to get rid of parasites (harboring in fur) that spread disease
1.8 (1st wave) - 0.065 (3rd wave)	The cause(s) of global migration from Africa	Overcrowding in the Horn of Africa pushed our ancestors to look for living space
0.024	Who or what is responsible for the extinction of Neanderthals?	Finger points to the crime of H. Sapiens, but it could be climate change as well.

Table 10-07 Riddles of Human Evolution

See "New Scientist", 24-30 March 2012 for more details.