Discuss
The Potential Significance Of Differences In Hominoid Chromosome Number In
Human Evolution
Archaeological Genetics essay, Algis Kuliukas, March 2001
Full version. (An
abridged version also submitted)
Abstract
Assuming that speciation relies on reproductive
isolation, creating the opportunity for genetic barriers against gene flow to
evolve, this thesis argues that chromosomal rearrangements are the most
important factor involved in this process. Considering that humans and/or great
apes have undergone several such aberrations since the last common ancestor
with the Hominoidae (including, most notably, a reduction in human
chromosome number from 48 to 46) this study investigates the significance of
these phenomena and scenarios for how and when they might have occurred.
It concludes that the chromosome number change, when it arose, not only
caused our own speciation event but probably also created a severe barrier
against interbreeding between the nascent Homo sapiens and the majority
of other extant hominids species at the time. It is postulated that the most
plausible scenario that could have resulted in a sufficient number of viable
individuals with this new chromosomal arrangement is a hybridisation of two
populations of hominids at the most 3.7 million years ago but possibly as
recent as 200,000 years before present.
Contents
2. What made us Human? Speciation &
the Role of Reproductive Isolation
2.1 What is a human being, what is a
species?
2.2 The Morphological Species
Concept
2.4 Reproductive Isolation and
Chromosomes
3. Human & Hominoid Karyotypes
3.1 What actually are chromosomes?
3.2 Chromosome identification and
classification
3.3 Chromosomal aberrations in
Meiosis
3.4 What are the chromosomal
differences of the Hominoidae?
4. Chromosome Numbers: Variation in
Primates and its Implications
4.1 A review of chromosome numbers
generally
4.3 Implications for postzygotic
reproductive isolation.
5. Scenarios for Chromosome Number
Change
5.1 Current theories of chromosome
number reduction and other rearrangements
5.2 Criticisms of the existing
models
5.3 A model for chromosome reduction
based on natural hybridization
6. Implications & Scenarios for
Human Evolution
7. Questions & Ideas for further
study
1. Introduction
Perhaps one of the most often quoted scientific facts in the last few years has been the one highlighting how genetically close humans are to chimpanzees. ‘More than 98% of our genes are identical’ is typical of the kind of statement found in both popular and scientific literature. Indeed, the sequence homology of both coding and noncoding DNA in humans is very similar to chimpanzees, (for example see Goodman et al. 1998) as it is to bonobos, gorillas and orang-utans. This is hardly surprising, however. Considering that perhaps as much as 40% of the genome in every living organism codes for proteins that are essential for general intracellular function, it is little wonder that a group of closely related mammals should have a very high percentage of common genes.
There is another even simpler, numeric, genetic fact about humans and chimpanzees that is not so often cited. Instead of emphasising our similarities it actually differentiates Homo sapiens from the other hominoids: It is the number of chromosomes.
All the great apes, that is both major taxa of Pan, P. paniscus (bonobo) and P. troglodytes (‘common’ chimpanzee) as well as the subspecies of Gorilla and the subspecies of Pongo (orang-utan) have 48 chromosomes whereas we have 46.
Applying the simplest principles of parsimony to this
observation it would seem fairly obvious that the last common ancestor of the Hominoidae
(that is the great apes and the hominids) had 48 chromosomes too. A simple
cladogram of this indicates that 48 (often written 2n = 48) chromosomes
is the primitive condition and that descended from that ancestor only
humans have the derived condition of 46.
This essay aims to investigate the significance of this phenomenon in understanding what happened to the hominid line. Specifically the objective is to review the existing models that have been used to explain how macromutations (chromosomal rearrangements) occur generally and chromosome numbers change specifically and to apply those to the hominoid situation to see what implications they might have for understanding our evolutionary past.
Before attempting that, however, some background material must be covered. The essay starts with the thorny issue of what species are and the role that reproductive isolation generally and chromosomal differences specifically may play in their evolution. Before we can discuss hominoid evolution we should be clear on the different taxa contained in the family and be clear on what distinguishes them genetically.
A very short review of the role of chromosomes in meiosis will be presented to aid this understanding as well as a summary of chromosomal terminology and systematics. This review will include a summary of known chromosome aberrations, emphasising those thought to have played a role in evolution.
The essay then zooms into a discussion of molecular genetics to review how chromosome numbers change according to current genetic theory. This involves scenarios that explain both how mutations cause such changes in the first place and how the new chromosome number can become fixed in populations. This discussion leads onto theories of chromosomal speciation including those that argue that chromosome number change might well be an essential requirement of it.
Finally it is argued that the strongest of the current models explaining chromosome number change are those that allow the possibility of hybridisation. Evidence for hybridisation is briefly reviewed both generally in nature, and specifically for the theory that Homo sapiens is the result of the hybridisation of two hominids. The essay concludes by considering the implications of such a hybridisation event on our understanding of human evolution.
2. What made us Human? Speciation & the Role of
Reproductive Isolation
2.1 What is a human being, what is a species?
The most basic of biological problems, that of defining what a species is, continues to cause difficulty (some would say “elude us”) even to this day.
Løvtrup (1979, p 388) summed up the predicament when he wrote “The unit of evolution is the terminal taxon, the interbreeding population which is an objective reality. All living beings belong to a terminal taxon, but whether or not a given species is a terminal taxon is unpredictable, being dependent of future discovery.”
If we aren’t clear what a species is we shall surely struggle to understand what happened to our ancestors to make us different from chimpanzees.
As far as this study is concerned the aim in defining ‘species’ is simply to establish the importance of the reproductive isolation generally and chromosomal incompatibilities specifically. The goal is to see what significance there may be in chromosome number difference between humans and the great apes.
2.2 The Morphological Species Concept
The earliest concepts of species were closely tied to taxonomy. The Linnaean naming system was an attempt to categorise the vast numbers of species into some order for our convenience. The only real basis upon which this was attempted was on the structure, or morphology, of the species.
Among the criticisms of this concept was the obvious point that often conspecifics have greater morphological differences (for instance manifested as sexual dimorphism) than members of closely related species. More seriously, as far as this argument goes, the concept ignores the issue of breeding compatibility.
Despite these criticisms the concept remains important to the general public and probably always will be. To the layman’s eye there is little doubt that humans, chimpanzees, gorillas and orang-utans are all different species, for instance.
Coming up with a definition of “species” which satisfies the critical minds of scientists has proved much more difficult.
It is beyond the scope of this essay to review the different ‘species concepts’ in detail. The reader might like to see White (1978) for a full account or King (1993) to see the particular points covered in this essay discussed more fully. However it is important, for the logic of this argument, to establish the importance of reproductive isolation in speciation.
2.3 Other Species Concepts
2.3.1 What is a species?
Species concepts, like species themselves, have been categorised in various ways. Like the species they try to define they are often blurred at the edges and the result of a splitting from or merging together of previous ones.
Most seem to have been formulated to tackle the particular biological problems of the scientists behind them. For instance in the study of evolution the concept of temporally sequential species is very important but was not perceived to be covered by existing concepts and so Simpson (1961) came up with The Evolutionary Species Concept which was then modified and improved by Wiley (1978.)
It is more difficult to place species on the basis of their fossils than from observing them alive in the field and in paleoanthroplogy there is huge controversy about such placements. For example, there is debate about whether Homo erectus should include Homo ergaster in the same paleo-species or be placed separately.
In searching for common ground, all the concepts require an
element of reproductive isolation in them although they differ in degree and
how they see that isolation arising. Some (e.g. recognition species concept –
Chimpanzees and bonobos are categorised as separate species
even though genetically they are only as diverse as the chimpanzee sub-species P.
t. verus, P. t. schweinfurthii, P. t. troglodytes are from each other, as
graphically shown by Gagneux (2000.) There is reproductive isolation between
them in the field, but only in the form of the main branch of the
To cut a long story short it will be argued here that Mayr’s (1969) modified definition of the BSC that “Species are groups of interbreeding populations which are reproductively isolated from other such groups” is still as good a definition as we have and it’s emphasis is the one that will be used in this study.
The BSC seems to have stood the test of time despite some problems and criticisms of it putting too much emphasis on reproductive isolation. Sokal and Crovello (1970) for instance, pointed out that if a hybrid of two ‘species’ is able to successfully backcross with either of the two parental populations then it would imply, if the BSC is applied strictly, that the two parental populations must belong to the same species. Bonobos and chimpanzees have been known to have produced viable offspring in captivity (Sommer 2000 pers. comm.) providing evidence that according to strict adherence to BSC they should not be classified as separate species.
The problem appears to be that reproductive isolation is not a binary condition. There are degrees of isolation and a full range of variability between extremes. Also there is variability in the viability of the F1 and F2 generations and their ability to backcross with the parental populations. Hybrids might well be less fit (negatively heterotic) than their parents but still able to reproduce.
Another difficulty is perhaps the natural desire that definition of species should tie in with the understanding of a word we have used already for so many years. So rather than accept the logical conclusion that the successful hybridisation of two populations seen as separate ‘species’ proves that parental populations had actually been from the same species technically, the tendency is to shy away and, instead, conclude that something is wrong with the definition. We forget that the word ‘species’ is a man-made term even though the concept underlying it is an objective reality. Perhaps we just don’t yet fully understand the concept.
Possibly the most counter-intuitive feature of the BSC is that it deals exclusively with sexually reproducing organisms. Only “interbreeding” populations can be defined as species according to the definition. It feels wrong to deny those organisms that reproduce asexually entry to the ‘species club’ and this was one of the main motivations for scientists to look for better concepts. But could it be that it is our perception that is wrong, not the concept? Perhaps the species concept really is one that has exclusively arisen out of sexually reproduction and that the problem of asexually reproducing organisms (where genetic barriers to interbreeding are always there by default) is a special case that needs treating separately.
Even if the BSC is deficient in not dealing with asexually reproducing organisms there undoubtedly appears to be some kind of link between speciation and the process of meiosis. It is a link that suits the argument of this essay. This will become apparent in the next sections as we move on to examine the mechanisms that might enforce permanent genetic barriers to reproduction.
2.3.2 How are species formed?
Along with the concepts which define ‘species’ there are a related set of theories about how speciation occurs. Most widely known and referred to are allopatric, parapatric and sympatric speciation (Where genetic changes leading to speciation occur in isolation, across an environmental grade in the same zone or without a grade in the same zone, respectively.) See section 5.1 for more on this.
2.3.3 Allopatric speciation and genetic distance
The classical view of allopatric speciation (where two populations gradually diverge and eventually speciate after becoming geographically isolated from each other for a period of time) is, according to King (1993 p 31,) due to the accumulation of genetically based differences. “Nevertheless,” he writes “the precise means by which this occurs remains as the most controversial aspect of this mode of speciation.”
Several workers have tried to tackle the problem by studying the rate of evolution of specific loci. For example, both Ayala’s (1975) and Lewontin’s (1974) work on Drosophila willistoni used protein electrophoresis to judge the genetic distance between two populations and looked for a correlation between this and hybrid viability. Both proposed that genetic changes occurred in distinct phases after reproductive isolation had been attained but differed in when they saw the most significant changes.
It would seem that their phases were rather arbitrarily defined however. Phase 1 for Lewontin, where little genetic change was detected, is different from phase 1 for Ayala, where a great deal of change was reported. Also there would seem to be a problem with using protein electrophoresis data as evidence for genetic barriers to gene flow. These barriers may arise on very specific isolated loci even though generally protein structure might be very similar. If such an analysis was done on haemoglobin, for instance, very little difference would be found between humans and chimpanzees even though the two species have quite significant genomic differences.
As Forsdyke (1999) put it… “it was apparent from the outset that the form of reproductive isolation likely to apply most generally to initial species divergence (hybrid sterility), would depend on differences, not in ‘primary’ information (‘genic’), but in ‘secondary’ information (‘chromosomal’).”
His paper proposed two levels of information stored in DNA and that it was changes in the chromosomal (‘packaging’) level that was most likely to cause barriers to gene flow, not genic ones.
So what conclusions might be drawn in this area?
It would seem clear that, when considering allopatric speciation, the amount of time that the two populations have been separated is of crucial importance.
It must be true that if two populations of the same species became separated for only a short period of time (say as little as 50,000 years – the estimated time since the last common ancestor of Europeans and Australians,) sufficient genetic drift would not have occurred to result in any barrier to gene flow between the populations. Their hybrids in both F1 and F2 generations would be viable and fertile both with each other and when backcrossed with the parental groups. Essentially they would have remained the same species.
Equally irrefutable is that if two populations became separated for a very great amount of time (say 130 million years – the estimated time since the last common ancestor of the kangaroo and the common British shrew) there would undoubtedly be more than enough time for sufficient genetic changes to have arisen to cause a permanent barrier to gene flow even if a hybridisation of the two species was attempted in the laboratory.
The interesting question is what happens in between? Somewhere in between these extremes there is undoubtedly going to be a situation when the two species have separated long enough for hybridisation to be problematic but possible. The hybrids might be negatively heterotic and most may not be viable but some may be. The question is what genetic factors would contribute to the success or otherwise of the hybrids of such parents? And what resulting genetic variation might one expect to see in such individuals?
It is to this question that we will now turn.
2.4 Reproductive Isolation and Chromosomes
According to King (1993, p 30) “the most functionally obvious difference between biological species is the attainment of reproductive isolation.” There are many factors that may cause this isolation. Some, like geographical, seasonal, behavioural, mechanical or physiological, are prezygotic. Other barriers are postzygotic and largely based around hybrid non-viability
However it could be argued that only postzygotic mechanisms are ‘real’ and permanent. For example geographical barriers can disappear. Some human ‘races’ are a good example of this. Whilst geographically separated for thousands of years gene flow between some populations was all but stopped. But even that was not enough for speciation to have occurred, and viable hybrids (possibly even fitter than their parents) have resulted now that technology has brought the species so close together again.
Prezygotic reproductive isolation creates an opportunity for speciation but something more is needed for it to actually occur and become fixed. Even species recognition and other, e.g. morphological, pre-mating barriers in the field may potentially be overcome in the laboratory.
It is important to keep in mind, however, that in the field
these barriers are real. King (1993
p 208) himself, a chief proponent of chromosomal speciation, reminds us
that “chromosome change is not a sin
qua non for speciation.”
Central to issue of genetic reproductive isolation is the viability of hybrids. King (1993, p 32-33) specifies the importance of including the absence of F2 generation or backcross hybridisation in defining this barrier and promotes Key’s (1981 p 455) definition of reproductive isolation.
“.. the relationship between two populations that do not
hybridise in the field, although in contact with each other, or, if they do,
whose F1 hybrids leave no progeny of reproductive age, i.e. are infertile
interse and in every backcross.”
Before we investigate how chromosome change may result and how it might effect the interbreeding of populations we must first get a background to their function and how they are organised. To do so we will focus in on the organisation of the human genome.
3. Human & Hominoid Karyotypes
In order to investigate the differences between the chromosomal structure of humans and our nearest relatives in the animal kingdom it would be logical to first get an understanding of how genetic material is organised in humans. This section will outline some basic chromosomal terminology whilst describing how chromosomes are organised in human beings. We will then be in a good position to contrast the differences at this level between us and the other hominoids.
3.1 What actually are chromosomes?
Chromosomes are structures which wrap very long, thin DNA molecules up into highly compressed packages at those times in the cell’s life cycle when it undergoes cell division.
They do so in a very complex way, using a set of very evolutionarily conservative proteins, called histones. This elaborate structure is beautifully illustrated in Fig 1 overleaf.
Fig 1 Chromosome Structure
Normally chromosomes exist in the nucleus of the cell in a diploid (or paired) state. However during cell division they sometimes split into a haploid (or single chromosome state.)
The detailed structure of chromosomes is not the subject of this essay but it is important, to understand some of the theories discussed later, to get a brief overview of some of the terminology used to describe their features.
3.2 Chromosome identification and classification
3.2.1 Early Classification
According to Strachan & Read (1999 p 44) it was only when banding techniques were developed in the early 1970s that individual chromosomes could be unambiguously identified.
Before that the karyotype of an organism (the
description of its compliment of chromosomes, including their number, size,
shape and internal arrangements) could still be determined from images taken
from cells in metaphase. The resulting paired chromosomes were then arranged
and numbered accord to their size and shape but distinguishing between
chromosome pairs was much more problematic than it is now. The techniques that
were used to do this are clearly outlined by Bender & Chu (1963 p 261.)
Pairs of chromosomes observed in this way are clearly
connected via a common centromere and were classified according to the
shape this made in relation to the arms of the chromosomes leading away from
it.
Metacentric chromosomes have a centromere in the middle, whereas the term submetacentric indicates that the centromere is not central. acrocentric chromosomes have them close to one end and telocentric chromosomes are joined right on the tips.
3.2.2 New Banding Techniques
Before sophisticated staining techniques revealed complex banding patterns, however, individual chromosomes were difficult to tell apart. Since then various banding techniques have revealed a much greater detail of chromosome structure making them much easier to identify.
For example G-banding produces a high resolution, high contrast image of chromosomes. They are subject to controlled digestion with trypsin before staining with Giemsa (a DNA binding dye.) Q-banding uses Quinacrine as a dye. Chromosomes treated in this way have to be viewed with uv fluorescence but show essentially the same banding as G bands. R-banding shows the reverse pattern of G banding. By carefully applying these dyes, sub-bands and sub-sub-bands can be identified.
Along with the improved resolution of detail came new naming standards based on the different lengths of the arms of the chromosome extending away from the centromere. The shorter arm is always termed the p arm (p for ‘petit’) whilst the longer arm is termed q (the next letter of the alphabet.)
According to the standard, distinctive regions of chromosomes are numbered, counting out from the centromere, p1, p2, p3 or q1, q2, q3 etc., depending on which arm of the chromosome the band is on. The chromosome is indicated too, so 12p3 is the 3rd band on the small arm of chromosome 12. Within the regions bands are numbered in a rather unusual hierarchical way. Bands are numbered p11, p12, p13 etc. but sub-bands are labelled p11.1, p11.2, p11.3 etc.
The complete systematic map of human banding patterns is shown below in fig 2. (Taken from Strachan & Dean 1999 p 46.)
Having been reminded of the function of chromosomes and introduced to their classification and labelling and having established, earlier, the importance of meiosis in speciation and specifically in postzygotic reproductive barriers, it is now time to tie these two strands together and begin to examine how chromosomal rearrangements may interfere in meiosis and potentially contribute to speciation events generally, and humans in particular.
3.3 Chromosomal aberrations in Meiosis
For most of the cell’s life cycle it is in a state called interphase. Although this is not actually a period of genetic inactivity, it appears so because it is the part of the cell cycle where the chromosomes pairs, as defined above, are not visible. At this stage much of the DNA in chromosomes is unravelled in a form called chromatin.
There are two types of cellular division where chromosomes do appear: mitosis (normal cell division retaining the diploid number of chromosomes) and meiosis (a special, more complex, type of cell division in sexually reproducing organisms which produces gametes (sperm and egg cells) with a haploid number of chromosomes.)
It is the process of meiosis that is most strongly implicated in producing genetic variation therefore, as it is also the process responsible for producing gametes in sexually reproducing organisms, it is also logically the most likely place to find the mechanisms that create barriers to gene flow between populations.
3.3.1 Meiotic phases where chromosomal aberrations may occur.
The process of meiosis is highly complex and intricate and it is not surprising that it includes a number of phases that are well known to give rise changes in gross chromosomal structure. In particular, the prophase of meiosis I the sub-phase called pachytene, where ‘crossing over’ occurs, is prone to mutations.
Another phase with potential problems is anaphase of meiosis I, meiosis II or the mitotic division, where the process of disjunction may not work properly.
Finally, the phase called synapsis, where the haploid chromosomes of the gametes fuse together again, is also a potential problem area.
There will now follow a brief review of the main known chromosomal anomalies in meiosis.
3.3.2 Segmental aberrations
3.3.2.1 Deletions.
Deletions are where a chromosome breaks in one or more places. There are two main types of deletion. A terminal deletion is simply where an end of one chromosome breaks off and an intercalary deletion involves two breaks in a loop of DNA resulting in a deficiency in the middle of a strand. Deletions are most likely thought to occur during the crossing over (pachytene) phase.
According to Klug & Cummings (1997 p 264) “a deficiency [or deletion] need not be very great before the effects become severe.” This may, at first sight seem surprising because it is likely that it would be paired with a normal and complete homolog. However it could be that the deletion may ‘unmask’ another damaging gene on that homolog. Alternatively it may be due to related problems during the fusion of haploid DNA in fertilization. Heterozygote chromosomes pairing with homologs with intercalary deletions may ‘buckle out’ into what are called compensatory loops. This loop might prevent the heterozygote (normal) genes from being expressed properly.
3.3.2.2 Duplications.
Duplications are said to have occurred when a part of genetic material is repeated. This aberration is also believed to arise during crossing over in meiosis, specifically where an unequal crossing over between synapsed (fused) chromosomes has occurred resulting on one chromosome with a deletion and one with a duplication.
Because duplications may also cause compensatory loops when fused with a normal heterozygote, they also have the potential to be very harmful.
However, duplications are also thought to be a potential mechanism for generating genetic variation. Ohno (1970) suggested that duplications of essential may have been tolerated or even increasing the fitness of the individual in the short term. Over a longer term he suggested that slight mutations in these duplicated genes may then give rise to new gene products that gave adaptive advantage. A body of genetic and molecular evidence backs up the idea. Genes with substantial similarities often code for similar but distinct proteins indicating that they may well have evolved in this way.
3.3.2.3. Inversions.
Another class of structural rearrangement is the inversion, where a segment of a chromosome is cut out, rotated through 180˚ and stuck back in again.
Again this is thought to be most likely to occur during the crossing over phase of meiosis, where a loop of chromosome undergoes four breaks but then rejoins the wrong way around.
If the centromere is part of the inverted segment it is said
to be a pericentric inversion and may result in the p, q arm lengths
changing. If the centromere is not inverted the arm lengths are not altered.
This is called a paracentric inversion.
Although theoretically no genetic data is lost through inversions they can still have profound effects. The consequences of inversions during gamete formation are quite complex. Inversion heterozygotes (where one chromosome has an inverted segment whilst its homolog is normal) can only pair if they form what is called an inversion loop.
The main feature of the inversion loop is that it is particularly sensitive to cross overs. In paracentric inversions it may result in chromosomes that are dicentric (with two centromeres) and acentric (with none). Even in pericentric inversions it may produce chromosome products that are fatally flawed.
The evolutionary consequence of this is that inversions are thought to maintain sets of specific alleles adjacent to each other. If these give a survival advantage to an individual the inversion may be net beneficial to the survival of its descendants.
3.3.2.4 Translocations.
Translocations are where a segment of a chromosome changes position and is placed somewhere else. Often this is a reciprocal translocation, where two non-homologous chromosomes swap a slice of their DNA.
Like inversions, translocations do not result in loss of genetic data and they also may result in unorthodox synapses during meiosis.
A special and quite common case of translocation is called a Robertsonian translocation or centric fusion. This is where two nonhomologous acrocentric (with centromeres towards one end) chromosome pairs undergo simultaneous breaks in their p (short) arms. The breaks are at the ends proximal to the centromere. The short acentric fragments are lost and the larger segments fuse at their centromeric region producing a new metacentric or submetacentric chromosome.
3.3.3 Whole chromosomal aberrations
In this section more severe chromosomal aberrations are considered. Polyploidy, where more than two whole haploid sets of chromosomes are present, is treated very quickly. Aneuploidy, where one or more (usually just one, but never a complete set) chromosomes is gained or lost is considered more fully.
First are those aberrations which change the basic chromosome number.
3.3.3.1 Chromosome fusion and fission
This first category of aberration has rather arbitrarily been separated from the segmental aberrations simply because they do result in a different number of chromosomes. However they could just as correctly been placed with the previous section.
As far as this study has been able to ascertain there are two recognised mechanisms for chromosomal fusion according to current genetic theory: The centric fusion and the tandem fusion.
‘Robertsonian’ Centric Fusions
Michael J. D. White (1978 p 53) describes the essence of what has become the most commonly held genetic mechanism behind chromosome number reduction in an authoritative but rather user-unfriendly way...
A great many cytotaxonomic differences between closely related species are of the so-called Robertsonian type (after W. R. B. Robertson, Kansas cytogeneticist, who in 1916 described some instances of centric fusions in grasshoppers), where a metacentric, V-shaped chromosome in one species is represented by two acrocentric, rod-shaped chromosomes in the other. This may lead to centric fusion between two acrocentrics (leading to the decrease in chromosome number) in one species or dissociation (producing an increase in chromosome number) in the other.
Such a concept could have been illustrated much simpler in a diagram but White made no such attempt in his book.
The following figure, taken from King (1993) which was redrawn in part from John and Freeman (1975) illustrates the concept of centric fusion much clearer and also shows the different types…
Fig 2 (from King 1993
p 76)
Summary of six of the possible forms of Robertsonian fusion.
Tandem fusions
Tandem fusions are those involving a direct union of one chromosome’s telomeric region with another’s. It is also possible that the fusion is telomeric-centromeric. Little genic loss is associated with this kind of fusion but they are thought to be quite harmful.
Nonetheless King (1993 p 74) lists a number of papers that have shown that several species can be distinguished by tandem fusions.
In fact since 1991 it has been thought that human chromosome 2 is the result of a telomere-telomere fusion (See section 3.4.1.) of two ancestral hominid chromosomes.
It is not known how viable such an individual would be with such a dramatic chromosomal aberration but there is some recent evidence that suggests that it might not have been totally inviable. Zneimer & Stewart (1999) published a case of a child born with a syndrome that was found to be a telomere-telomere fusion of chromosomes 7 and 22.
3.3.3.3 Aneuploidy
Where the addition or loss of one or more (but not an entire set) of whole individual chromosomes occurs it is aneuploidy. The loss of a chromosome is called monosomy, the gain of one, trisomy.
The table below (taken from Klug & Cummins 1997 p 252) gives a full list of terms.
|
Term |
Explanation |
|
Aneuploidy |
2n ± chromosomes |
|
Monosomy |
2n – 1 |
|
Trisomy |
2n + 1 |
|
Tetrasomy, pentasomy etc. |
2n + 2, 2n + 3 etc. |
|
Euploidy |
Multiples of n haploid sets of chromosomes |
|
Diploidy |
2n |
|
Polyploidy |
3n, 4n, 5n, … |
|
Triploidy |
3n |
|
Tetraploidy |
4n |
|
Autoployploidy |
Multiples from same genome |
|
Allopolyploidy |
Multiples from different genomes (hybrid) |
Polyploidy is discussed in the next section.
The most common cause of aneuploidy is thought to be from nondisjunction when chromosomes fail to separate during segregation in anaphase.
Several syndromes have been identified in humans where this happens. Some, for instance Klinefelter syndrome and Turner syndrome, involve the gain or loss of one of the sex chromosomes whilst others involve autosomes (chromosomes other than X and Y.)
Monosomy, the loss of a chromosome, is almost always lethal which is thought to be due to the unmasking of other lethal alleles.
Generally trisomy, the addition of a single chromosome, produces more viable individuals than monosomy but rarely viable enough to survive for long. Studies (Carr, 1970) of spontaneously aborted human foetuses have shown trisomies for all 23 human chromosomes. No monosomies were found in the study, suggesting that gametes lacking a chromosome are so impaired they do not survive to fertilization or that the embryo dies very early in development.
The only syndrome involving autosomal aneuploidy in humans in which a significant number of people survive longer than their first year is Down syndrome, otherwise known as trisomy 21, where three copies of chromosome 21 exists. (Hence it is designated 47, + 21.)
Like other trisomies, it is thought to occur through the nondisjunction of this chromosome during either anaphase I or anaphase II of meiosis. This creates a gamete with n + 1 chromosomes which, when fused with a normal gamete, forms the trisomy situation.
Although people with Down syndrome are known to be able to live happy lives their life expectancy is significantly shortened and they are prone to several illnesses, for example leukaemia and respiratory diseases.
The fact that of all the 23 chromosomes only trisomy 21 produces people that live beyond one year shows how sensitive organisms are to such macromutations. As Klug & Cummings (1997 p 258) put it… “The prenatal mortality of most aneuploids provides a barrier against the introduction of a variety of chromosome based genetic anomalies into the human population.”
Even relatively small mutations on the genome, such as CLN2, a deletion to a gene located on 11p15 of 6.65kb, causes one form of the lethal children’s disease of Neuronal Ceroid Lipofuscinoses (NCL or Batten Disease) when exposed as a homozygote condition. (Williams et al 1999 p 46.)
Bearing in mind all this sensitivity to chromosomal mutations, it is a wonder that chromosome number ever changes at all. Clearly they do. The ancestral hominoid 24 x 2n karyotype has indeed evolved into the 23 x 2n we find in humans today.
3.2.4 Whole set aberrations: Polyploidy
Most cells contain two complete sets of homologous chromosomes. This state is called diploid meaning ‘two sets of chromosomes’. The gametes have half of this number, hence haploid. There are situations, however, when a cell has an entire extra set of chromosomes, (triploid) or perhaps even more (tetraploid, pentaploid etc.)
Polyploidy is relatively common in plants. In fact, according to Arnold (1997 p 11) “it has been estimated that from 30% to 70% of all angiosperm species are polyploid relative to one of their ancestral lineages.” Allopolyploidy (the increasing of one or more, usually two, haploid sets through hybridisation) is a normal and accepted mode of speciation. However in animals, where species recognition is much more controlled, it is much rarer. Nevertheless, according to Strachan & Dean (1999 p 48) in humans between 1 and 3% of pregnancies are triploid.
Animal polyploidy is thought to occur through the multiple fertilization of a single egg or dispermy. Triploids very rarely survive to term and the condition in lethal.
3.4 What are the chromosomal differences of the Hominoidae?
Humans and great apes have very similar genomes. According to Strachan & Dean (1997 p 345.) They are of similar size (estimated at 3,000 Mb and between 65,000 and 80,000 genes.) Gene families (where genes appear to have evolved from others through duplication) appear similar across all four species. The genomes exhibit the well publicised sequence homology described earlier, at over 98%, and telomeric repeat sequences appear to be highly conserved among them all. But perhaps the most striking similarities, and obvious differences, come to light when comparing chromosomal banding patterns.
Yunis and Prakash (1982) studied the karyotypes of humans and the other great apes. By using banding techniques they were able to compare their chromosomes and attempt to trace the major chromosomal aberrations that appear to have happened in the evolutionary history of the hominoidea.
Perhaps not surprising, bearing mind how closely related we are to the great apes, 20 of the 23 chromosomes appeared almost identical.
They found aberrations on only three: chromosomes 2, 5 and 6.
3.4.1 Chromosome 2: A fusion of ancestral chromosomes 2 & 3.
The most significant gross chromosomal difference between humans and chimpanzees is reduction by one of the haploid chromosome number.
What appears to have happened is that at some time since the Pan/Homo split, two chromosomes of a primate ancestor fused into one. It is most parsimonious to assume that this happened since the split with the apes because Gorilla and Pongo have the same, ancestral chromosomal structure.
The fusion of what might be termed ancestral chromosome 2 & 3, appears to have occurred on both p arms, close to the telomere, losing one of the centromeres and some genic material, from the two p arm tips, in the process.
According to the visible evidence of banding patterns, the modern human chromosome is fused at the point 2q13.
Although this was originally believed to be the result of a centric fusion, Ijdo et al. (1991) found that the fusion resulting in human chromosome 2 was a telomere-telomere (tandem) fusion.
3.4.2 Chromosome 5: A pericentric inversion and a reciprocal translocation
The chimpanzee chromosome 5 is very similar to humans’ except for one significant aberration: a pericentric inversion (one including the centromere.) The inverted segment is very large – from 5p13 to 5q13.
Also a reciprocal translocation appears to have taken place between chromosome 17 and the chromosome 5, but this is only apparent when human and gorilla karyotypes are compared. The translocation is not apparent when comparing human and chimpanzee chromosomes, or those of the orang-utan. Because the pericentric inversion, discussed previously, is only apparent when comparing human and chimpanzee (and not gorilla) chromosome 5, it would appear that the reciprocal translocation occurred independently on the gorilla line since the Pan-Homo split.
3.4.3 Chromosome 6: A small terminal deletion
Finally, on chromosome 6 a relatively small deletion of telomeric heterochromatin (DNA that remains condensed even during interphase and is therefore thought to be predominantly noncoding) on the p arm appears to have happened.
Surprisingly this aberration is also on Pongo but not Gorilla, indicating that it happened twice (once on the hominid line and once on the Pongo line.) The alternative explanation – that Homo and Pongo split since the two split from Pan/Gorilla is contradicted by the two other macromutations discussed here, and most other genetic and molecular evidence. (again see Goodman et al. 1998)
The chromosomal rearrangements are summarised below.
Fig 3 - Human chromosome banding patterns compared to the great apes (From Strachan & Dean 1998 p 344)
Notes H, C, G, O for Human, Chimpanzee, Gorilla and Orang-utan respectively. Chromosomes 2, 5 & 6 shown only.
4. Chromosome Numbers: Variation in Primates and its
Implications
Earlier on in this discussion we considered what genetic barriers might have arisen that led to speciation events generally and our own specifically. Now, it would seem, we have found some. The first two (at least) of the three major aberrations discussed above would appear likely to contribute to, if not guarantee, reproductive isolation between populations. But do they? What is the evidence that chromosomal rearrangements such as this do stop gene flow between populations?
4.1 A review of chromosome numbers generally
As White (1978 p 45) put it “Not all species differ in their karyotype, but most of them certainly do.”
Throughout the amazing diversity of living organisms on the
planet there would appear to be little correlation between the number of
chromosomes and the organisms themselves. The number of chromosomes appears to
vary quite randomly across families, genera and taxa. Certainly there would
appear to be no selective advantage in having a greater or lesser number of
them generally. This is exactly what would be predicted if one assumed that the
only function of chromosomes was for genic (genetic information) packaging.
The following table, taken from Klug & Cummings (1997 p 23) illustrates the
point.
The Haploid
Number of Chromosomes for Diverse Organisms
|
Common Name |
Scientific Name |