Abstract
Since the first genomes were sequenced in the late 1970s, there has been a vast progression in the knowledge and understanding of genome evolution and scientists have been studying the differences and similarities between the various genomes of different species. Sex is determined genetically in mammals, birds and reptiles; mammal chromosomes are XX for female, XY for male and birds/reptiles are ZW for female, ZZ for male. Genes that are lost from specifically sex chromosomes can be found on the partner chromosome in a single copy in one sex and in two copies in the other, this can cause issues in equilibrating gene products between the sexes and interactions with genes on other chromosomes, i.e. Autosomes. The aim of this study is to examine the genes of the human and avian sex chromosomes in order to identify the homologous regions between them. whether there is any direct homology between the sex chromosomes in Mammals/Primates and Birds and if the sex chromosomes between these two species, could have originated from homologous chromosomes from their last common ancestor. This will allow us to also compare the evolutionary changes to the rate of recombination in vertebrates and to address the dosage compensation mechanisms and degradation of the sex-specific human Y chromosome and Chicken W chromosome. There are selective pressures causing the recombination of the chromosomes in birds and mammals. There is a clear difference in the rate of recombination in mammals and birds, with mammals showing more changes to the sex chromosomes and birds showing more changes to their autosomes. Therefore implying, G. gallus shares more with the common ancestor and the H. sapien autosomes than the sex chromosomes.
Introduction
Genome evolution is the process by which a genome structure alters over time; through mutation, gene transfer and/or sexual reproduction (Otto, 2002). Since the first genomes were sequenced in the late 1970s, there has been a vast progression in the knowledge and understanding of their evolution and scientists have been studying the differences and similarities between various genomes (Otto, 2002). The field is constantly changing and evolving due to the growing number of sequenced genomes, both prokaryotic (single celled organisms) and eukaryotic (Humans, nonhuman animals) available to not only the scientific community but also the public.
Sex is determined genetically in mammals, birds and reptiles; XX for female, XY for male in mammals and ZW for female, ZZ for male in birds/reptiles (Graves, 2006). Sex chromosomes evolved independently and are derived from ordinary autosomes; they are separated from autosomes by their sex determining genes and from each other by genes that are attained for either male or female determining function (Graves, 2016). All embryos are first female and in those where sexual determination is hormonal, the development of hormones causes them to become male (Graves, 2016). There are two classes of sexual hormone, Oestrogens, which allow the development of female sexual characteristics and Androgens, which cause the development of male sexual characteristics by triggering development for the testis (Graves, 2016) these hormones belong to a chemical group called sterols, which are the reason for sex chromosomes.
Synteny is the term given to the order in which a genome is in a sequence, Figure 1 shows how an autosome pair originally acquires a sex-determining allele on a male determining factor or a female determining factor, it also shows how degeneration occurs.
Sex chromosome evolution has provoked great curiosity over the last hundred years since Muller (1914) put forward the theory that the X and Y chromosomes may have evolved from a homologous pair (a chromosome with the same sequence as another) of autosomes (Livernois et al., 2012). Muller's thoughts correspond with that of Graves (2016), he proposed that one member of the pair developed a testis-determining factor, and there was selection for subdual of recombination to hold the sex-specific group of genes together (Livernois et al., 2012). In the absence of recombination, the Y degrades due to genetic drift, this is known as Muller's ratchet (Livernois et al., 2012). Drift is intensified by the reduced size of Y and selection is inefficient as it acts on the Y chromosome as a whole, rather than individual loci (Livernois et al., 2012). Muller's ratchet is a theory based on the effect of accumulation of vaguely harmful DNA changes in a population over generations which could lead to the extinction of species and is thus of considerable biological interest (Suh, et al. 2011).
Gene dosage imbalance
The term karyotype, refers to the full set of chromosomes from an individual; genetic testing allows the comparison of a questioned karyotype against a 'normal' copy of a species karyotype. Ploidy is the name given to the number of chromosomes in a biological cell, Antonarakis, Et al (2004) defined genomic aneuploidy as an 'abnormal number of copies of a genomic region' and it is a common cause of human genetic disorders (Antonarakis, Et al., 2004). Humans normally have 46 chromosomes in each cell which divide into 23 pairs; Two copies of chromosome 21, one inherited from each parent, form one of the pairs, chromosome 21 is the smallest human autosome (Makalowski, 2001).
Most people have two copies of chromosome 21, those with three copies of chromosome 21 have a genetic condition called Down syndrome, also known as "trisomy 21" (Antonarakis, et al., 2004) this is a prime example of dosage compensation. 'Trisomy' is the coping of whole chromosomes and monosomy is term given to the absence of chromosomes. For example, Down syndrome (Trisomy 21) occurs in 1 in 750 births, and is the most frequent trisomy event (Antonarakis, et al., 2004). Partial trisomies, that involve a genomic region of more than one chromosomal band are less common than whole-chromosome trisomies and they are usually the product of abnormal meisosis and isolation in individuals with balance chromosomal rearrangement (Antonarakis, et al. 2004).
Antonarakis et al (2004) suggested that "The completion of the high-quality nucleotide sequence of chromosome 21 can now provide the basis for the molecular analysis of trisomy 21". Mittwoch (1967) states that molecular evolution across different phytogenic groups is not consistent. Though gene mapping studies are consistent with primate chromosome morphology (Clark, 1996). Morphological changes can influence the perception of a species, though rearrangements to chromosomes are the most robust generators of reproductive isolation.
Sex linked disorders
Genes which are lost from sex-specific chromosomes are present on the partner chromosome in a single copy in one sex and in two copies in the other, this can cause issues in equilibrating gene products between the sexes and interactions with genes on other chromosomes, i.e. Autosomes. (Graves, et al., 2012) Different lineages and mechanisms compensate to a greater or reduced extent for the 2:1 gene dosage difference between the sexes. Graves (2015) referred to sex chromosomes as "dumb design: systems that make no functional sense but that can be understood in terms of evolution", through research it can be said that when the system works as it should, it is a highly intelligent structure, but it so easily goes wrong for no apparent reason.
All embryos are female until a hormone is introduced that is required to turn them male; in an article written by Callaway for New science (2009), it is described how a female in Switzerland was born with a copy of the Y chromosome; She had a normal chromosome count of 46 and should be male. According to published research (Antonarakis, et al., 2004) this should cause abnormalities such as shriveled testis or at least some developmental defects, however the girl had fully functioning, female reproductive organs with no abnormalities (Callaway, 2009). The extremely unique condition would not have been detected if not for the tests performed on the mother before birth to check for a variety of genetic defects, such as Down's syndrome. All performed tests came back negative and indicated the child would be a boy, this is an example of how simplistic our understanding of this process is, and why more research is necessary.
There is also speculation about the disappearance of the Y chromosome and its implications on the sex-chromosomes of men; The loss of Y occurs in up to 17 percent of men and is evidently more likely to be found in older men and men who smoke (Dumanski, 2016). In a study by Cell Press, Dumanski (2016) expands on the idea that the loss of the Y chromosome, is recognised risk factor for cancer and revealed that men who lack the Y chromosome have been linked to be more susceptible to Alzheimer's disease (Dumanski, 2016). Though this is only a theory and has not yet been scientifically proven, it is a thought-provoking concept as Alzheimer's affects up to 1 in 9 people over the age of 65 (Newman, 2016). This study also stands as a possible reason as to why men, on average, live shorter lives than women.
As previously stated, the Y chromosome contains multiple genes that are key to testes information; though the X chromosome preserved its size throughout evolution, with about 2000 genes; the Y chromosome lost a large amount of its genetic material early in its evolution, retaining less than 100 of those original genes (Graves, 2015). This led to some scientists hypothesising that the chromosome is largely unessential and could shrink away. Bellot et al (2016) compared the Y chromosome of eight mammals and discovered that the overlap was not only in the genes that are known to determine the sex of an embryo. Numerous diverse genes stood out as being highly similar between the species; The genes had extensive functions including controlling the expression of genes in many other areas of the genome (Bellot et al., 2016). The fact that species have retained their genes despite massive overall changes to the Y chromosome, insinuates that they're crucial to mammalian survival. Graves (2001) stated that the X and Y chromosome are thought to have evolved from an ordinary pair of autosomes that stopped recombining after acquiring a sex-determining role.
Due to the absence of recombination, these formerly homologous chromosomes continue to differentiate. The molecular characterisation of several Y chromosomes that derived between 1 and 10 million years ago, has begun in both plants and animals such as Drosophilia Miranda (Bachtrog, 2006) the most widely studied Y chromosome to date is that of D. Miranda; Although extensive progress has been made in identifying just how Y chromosomes degenerate and an important question to be answered is why they do so (Graves, 2016).
In this project the evolutionary implications of genomic evolution in relation to sex chromosome in vertebrates will be discussed at karyotype level, the original human sequence contains more info on the X chromosome than the Y, and this could be due to the vast information on the X and not the Y. The 'unguarded X heterogametic sex' hypothesis is based on the fact that, in mammals, males are the heteromorphic sex as they have one X and one Y, whereas females are homomorphic as they have two X (Bachtrog, 2006). Whereas in contrast, the female in birds/reptiles is heteromorphic having one Z and one W and males are homomorphic with two Z. The occurance of a female's two X's can prevent phenotypic exposure of a sex-linked deleterious allele whereas males have no second copy in order to compensate (Bachtrog, 2006). These are just a select few studies that focus on the consequences of those affected by the evolutionary changes in sex chromosomes.
First human genome sequence.
The first sequence of the human genome was published in 2001, two groups decoded it successfully and published their articles on the same date in separate journals; Nature (International Human Genome Sequencing consortium, 2001) and Science (Vetner, et al. 2001). Decoding the DNA of human (Homo sapien) genome was the key to understanding not only human evolution, but the causation of disease and the relationship between the environment and heredity in defining the human condition (Vetner, et al., 2001). The project of nucleotide sequence of the human genome was first proposed in 1985.
In 1977, Sanger (1977) reported a method for determining the order of nucleotides of species DNA using chain-terminating analogs, the first human genome was isolated in the same year. The project was first proposed in 1985 and was referred to as the 'nucleotide sequence of the human genome' (Sanger, et al., 1977).
Expressed sequence tagging (EST) led to the discovery and mapping of human genes;
The institute for genomic research (TIGR) developed an algorithm that allowed assembly and analysis of hundreds of thousands of ESTs. The algorithm allowed characterisation and annotation of human genes on the basis of 30,000 EST assemblies (Vetner, et al. 2001).
Avian species
Alfoldi (2011) stated that "the evolution of the amniotic egg was one of the great evolutionary innovations in the history of life" freeing vertebrates from life in water and therefore permitting the occupation of terrestrial environments. The amniote lineage evolved and divided into the ancestral lineages of mammals and reptiles 320 million years ago (Organ, et al. 2008). Today, the surviving members of those lineages are mammals, consisting of around 4,500 species, and reptiles, consisting of an estimated 17,000 species (Ballot. et al. 2017). Within the reptiles, the two major clades diverged 280 million years ago: the lepidosaurs, which contains lizards (including snakes) and the tuatara; and the archosaurs, containing crocodilians and birds (Burt et al., 1999). The thousands of existing bird species belong to two major subclasses, the Ratitae and the Carinitae, both of which evolved about 80 million years ago. Graves (2011) states that overtime reptiles separated from amphibians, which studies show, evolved from a branch of the bony fish 350-400 million years ago. Two of the major branches of reptiles, anapsids, e.g. turtles, and diapsids e.g. snakes and lizards and the ancestors of birds, are conventionally thought to have evolved between 300-350 million years ago, though recent evaluations of DNA sequence similarity show that despite the differences in their anatomy, turtles may truly originate from branch of the diapsids (Graves and Shetty, 2001). Birds and mammals shared their last common ancestor in the vicinity of around 300 million years ago, see figure 3. When birds diverged from mammals the ancestral autosomes evolved into sex chromosomes (Ballot. et al. 2017). The genome of a bird is less than half the size of the human genome with 38 chromosome pairs and 2 sex chromosomes, Z and W. In birds, females are homozygous (ZZ) and males are heterozygous (ZW). Avian W evolved at the same rate with mammalian Y, preserving ancestral genes through selection to sustain the dosage of largely expressed regulators of key cellular developments (Bellot, 2017). The avian species involved in this study is Gallus gallus a Galliform, domesticated form of the red Jungle fowl, native to Asia.
A dominant-active ovary determinant may be carried on the W chromosome, though alternatively, the dosage of a Z-linked gene may mediate sex determination, two doses being required for male development (ZZ). Smith et al (2009) conducted a research study on the avian Z-linked gene 'DMRT1' and its requirement in male sex determination. During this study, RNA interface (RNAi) to "knock down DMRT1 in early chicken embryos". It was found that the reduction of DMRT1 protein expression in ovo leads to the feminisation of the gonads in genetically male embryos. Males that were affected showed signs of partial sex reversal, thus being an area of interest for this study. The results of the study indicated that DMRT1 is key to testis development and therefore sex determination in G. gallus, it has orthologues to H. sapien where the DMRT1 gene is on chromosome 9.
Aims and objectives
The aim of this study is to examine the genes of the Primate and Avian sex chromosomes and to identify the homologous regions between them. The first question to be addressed is whether there is any direct homology between the sex chromosomes in Primates and Birds, if not, then we will investigate if the sex chromosomes between these two species, could have originated from homologous chromosomes from their last common ancestor. This will allow us to also compare the evolutionary changes to the rate of recombination in vertebrates and to address the dosage compensation mechanisms and decrease in size of the sex-specific human Y chromosome and Chicken W chromosome.
Sexual reproduction with some degree of gamete dimorphism is nearly universal among eukaryotes as a collective and for this to occur a male and female of the same species must be present, their sex determination relying on sex chromosomes and this study aims to investigate the synteny between genes in two different vertebrate classes, Human and Chicken in order to reveal whether the genes are homologous.
Hypothesis 1 – There is evidence of different evolutionary pressures in sex chromosomes in birds and humans.
Hypothesis 2 – There is degeneration of the heteromorphic sex chromosome in both species.
Methods
Collection of data
Data was obtained from 'Ensembl' database (see figure 4). The Ensembl project (http://www.ensembl.org) created and distributed genome annotations and provides united views of valuable genomic data for supported chordate genomes.
Primate sex chromosomes X/Y were mapped against Gallus gallus genome, and Avian Z/W were mapped against Homosapien genome. Species were first located using the drop-down search mechanism on the main page, selecting the "view Karyotype" button to reveal a view of the whole genome. The chromosomes were then located and selected (X/Y in H. sapien and Z/W in G. gallus). Clicking on the chosen chromosome. (Eg. X in H. sapien) gives you an option to 'jump to region view' or view the chromosome summary. Selecting 'jump to region view' takes you to a more in detail view of the chromosome and using the location search box, the start and end search points, also known as break points, can be entered.
Chromosomes X vs Y
The X chromosome consists of 155 million base pairs; Y has 80 million with information only on the first 40 million genes.
To view the genes orthologous to the respective species, I right clicked on a protein coding gene, this causes an information menu to pop up and selecting the 'Ensembl' name for the gene. Eg. ENSG00000102038. (see figure 5) Taking you through to a page of information on the chosen gene.
As the data was collected, the genes on chromosome X were compared with those on chromosome Y in order to inspect synteny. Genes with orthologous links between species and within species were investigated. It was noted that certain genes on chromosome Y were in the same location on chromosome X, these genes were investigated further, their function was then identified in order to see if the function was the same on both chromosomes.
Chromosomes Z vs W
Genes with an orthologous link to G. gallus from chromosome Z were then compared with those on chromosome W in order to inspect possible synteny and to later compare against the results of chromosome X and Y. The information found was documented in a separate excel sheet to the chromosome X and Y information, in order to avoid confusion.
X+ Y vs Gallus gallus
On the right side of the page, is a list of options to view within the gene, selecting orthologues (see figure 6) and scroll down to find if this gene has an orthologue with the chicken genome. If not, then the process was redone with other protein coding genes until two orthologues genes were found within the selection locations. Two protein coding genes with orthologues to G, gallus from every 10 million base pairs (bp) were documented from X and two from every 5 million bp in Y, due to lack of gene information on Y.
Z+W vs Homo sapien
The same method was used in order to inspect the H. sapien genes with orthologues to Z and W. Two protein coding genes were recorded from every 10 million bp in Z and two genes were recorded from every 1 million bp in W. Once orthologous genes were found the data was then documented using Excel, the gene ID, start and end point of location were recorded in separate sheets for each sex chromosome, in order to avoid confusion.
Results
Chromosomes X vs Y
Y START END X START END
PLCXD1 276,322 303,356 PLCXD1 276,322 303,356
GTPBP6 304,529 318,819 GTPBP6 304,529 318,819
AL732314.4 419,157 421,980 AL732314.4 419,157 421,980
SHOX 624,344 659,411 SHOX 624,344 659,411
AL672277.1 990,221 994,364 AL672277.1 990,221 994,364
CRLF2 1,187,503 1,212,740 CRLF2 1,187,503 1,212,740
CSF2RA 1,268,800 1,310,381 CSF2RA 1,268,800 1,310,381
MIR3690 1,293,918 1,293,992 MIR3690 1,293,918 1,293,992
IL3RA 1,336,616 1,382,689 IL3RA 1,336,616 1,382,689
SLC25A6 1,386,152 1,392,724 SLC25A6 1,386,152 1,392,724
AKAP17A 1,591,593 1,602,514 AKAP174 1,591,593 1,602,514
DHRSX 2,219,516 2,502,805 DHRSX 2,219,516 2,502,805
ZBED1 2,486,414 2,500,967 ZBED1 2,486,414 2,500,967
Genes highlighted in red have orthologous links to G. gallus.
PLCXD1 – phosphatidylinositol specific phospholipase C X domain containing 1 [Source:HGNC Symbol;Acc:HGNC:23148]
GTPBP6 – GTP binding protein 6 (putative) [Source:HGNC Symbol;Acc:HGNC:30189]
SHOX – short stature homeobox [Source:HGNC Symbol;Acc:HGNC:10853]
IL3RA – interleukin 3 receptor subunit alpha [Source:HGNC Symbol;Acc:HGNC:6012]
CSF2RA – colony stimulating factor 2 receptor alpha subunit [Source:HGNC Symbol;Acc:HGNC:2435]
SLC25A6 – solute carrier family 25 member 6 [Source:HGNC Symbol;Acc:HGNC:10992]
AKAP17A – A-kinase anchoring protein 17A [Source:HGNC Symbol;Acc:HGNC:18783]
DHRSX – dehydrogenase/reductase X-linked [Source:HGNC Symbol;Acc:HGNC:18399]
Z vs W
No synteny was found when investigating the genes on the Avian sex chromosome pair, genes were unique to their chromosome and had individual locations.
4. Discussion
While speciation from a common ancestor can be explicated by allelic mutations at already known gene loci, when evolution at the sub phylum vertebrata is considered, allelic mutations are therefore no longer enough to account for all the changes that have occured during the past 300 million years. Ohno (1967) stated that "Gene duplication now emerges as the prime factor of evolution" the stands today with authors such as Graves (2001) quoting and agreeing with the statement. Ohno (1967) acknowledged how gene duplication can be achieved through the following four methods: 1) By an unequal exchange between the two sister chromatids of one chromosome, 2) by the regionally redundant duplication of DNA molecules, 3) by the inadequate crossing-over between the two homologous chromosomes during meiosis, and 4) by polyploidization (Graves and Shetty, 2012).
While comparative gene mapping suggests that the primate XY and the bird ZW pairs are entirely non-homologous, differentiation of the sex chromosome pair appears to have kept to comparable pathways in mammals, birds and also in snakes (Graves, 2001). From observations on the Z, W sex chromosome pair in a study on snakes many decades ago, Ohno (1967) suggested that the W may have evolved from the Z by gradual degradation within non-recombining sex-specific regions (Graves, 2001). This hypothesis may also account for the different levels of ZW homology in various bird groups.
A similar pathway for mammal sex chromosomes X and Y differentiation is shown by evaluation of the similarities between the content of genes on the X and Y chromosomes, but this is made difficult in eutherian mammals by the expansions of both sex chromosomes due to the addition of autosomal segments. The differences in gene dosage in mammals between XX females and XY males are counterweighted by the inactivation on a large-scale, of one X in mammals, and this dosage compensation mechanism does seem to have an avian counterpart (Graves and Shetty, 2001). Therefore, presenting the question of how, two completely unique chromosomal sex determining mechanisms could have evolved independently and determined sex chromosome evolution on similar but individual pathways?
The three existing major mammal groups, the subclass Theria which contains, Eutheria "placental mammals" and Metatheria "masupials" diverged around 130-170 million years ago, in addition, Theria diverged from the Subclass Prototheria which are egg-laying monotremes who evolved even earlier in the 200-million-year history of the evolution of mammals (Graves and Shetty, 2001).
The mammal X and Y chromosomal pair and birds/reptiles Z and W pair are parallel with eachother, having one member remaining large and gene-rich and the other reducing in size, heterochromatic and lacking genetic development (Graves and Shetty, 2001).
The relationship between mammal and bird sex chromosome is still heavily researched, though the male is heterogamic in mammals and the female is heterogamic in birds, this does not mean they are unalike, given that it is feasible to develop a male dominant system for male heterogametry in mammals, and a dosage-related system for female heterogamety from the same chromosomal pair (Graves and Shetty, 2001).
Orthologues of G. gallus sex-linked genes are found on H. sapien autosomes 5,9 and 18, while the orthologues of human sex-linked genes are found on chicken autosomes 1 and 4. Orthologues of sex-linked genes are found on separate autosomes in different species, like fish, signifying that the sex chromosomes of birds and mammals evolved individually from what were once autosomes in their common ancestor (Bellot, et al 2016).
Chromosomes X vs Y
The human X chromosome contains around 1670 genes (http://www.ensembl.com) and is approximately 155 Mb, representing about 5% of the haploid, human genome (Livernois et al., 2012: Ross et al., 2005). Livernois et al (2012) states that though it is known as the 'female' sex chromosome, the X chromosome is not devoted to 'femaleness'; it encodes an assortment of widely expressed housekeeping genes, as well as genes retaining specialised functions such as visual pigments and blood clotting factors (Livernois et al., 2012). However, compared to the autosomes, there is an elevated frequency of genes with sex and reproduction-related functions (Saifi and Chandra, 1999). It has been suggested that the male advantage genes on the H. sapien X chromosome are the result of "rapid selection" in the hemizygous male (Livernois et al., 2012). Livernois et al (2012) indicates that "A new recessive allele will be expressed in males; as they only have one copy", thus, if it is a beneficial function within the sperm or gonads, it will be selected immediately. This will occur despite the function in females as there will be no phenotypic effect on the heterozygous females, the proportion of homozygous females will be minimal (Graves, 2006). In contrast to the X, the H. sapien Y is small at approximately 60 Mb (Results show that genes were found only on the first 24 Mb), it is gene poor and largely heterochromatic (Livernois et al., 2012). The male-specific region of the Y displays 156 genes which includes 78 protein coding genes though many of these are amplified meaning they collectively code for only 27 distinct protein coding genes (Shaletsky et al., 2003) aligning with other studies conducted on the H. sapien sex chromosomes, illustrating the degeneration of the Y chromosome.
Whilst comparing genes located on chromosome X with those located on chromosome Y, several genes were found in the exact same locations on both chromosomes, the protein coding genes can be seen in Table 1. These results are supported by Waters et al (2005), who states that of the 27 genes, 20 have partners on the X from which is hypothesised they evolved. Though for this study only the protein coding genes were studies, the further partnered genes can be found in the appendix. All that remains of the once broad homology with the X chromosome are these X/Y shared genes; unlike the X, there is a significant variation of the Y chromosome structure and content between eutherian species due to autonomous degradation in different lineages, for which can be seen in the results has stemmed to different but corrosponding subsets of genes on the Y chromosome with the X (Graves, 2006). These results therefore show synteny within the species. Several protein coding genes in the same location on X and Y were found to have orthologous to G. gallus see figure 8. showing synteny as genes map to similar location.
Chromosomes Z vs W
In birds, chromosome Z compromises an unchanging 7% of the haploid genome in different families, it is similar in size and morphology, and chromosome painting reveals molecular homology (Livernois et al., 2012: Shetty et al., 1999) but the W fluctuates (Graves and Shetty, 2001). Graves and Shetty (2001) also state that cross species chromosome painting with the Chicken Z chromosome reveals a non-hybridizing segment of the Emu W chromosome, that possibly consists of repetitive elements not present on the Z. As previously stated, Carinate birds have a small heterochromatic W, widely varying in size between different orders. For example, the chicken W consists of only around 1.5% of the entire genome (Clinton and Haines, 1999), and pairs with chromosome Z only over a small pseudoautosomal region at the tip of the short arm, which contains only a single recombination nodule (Graves and Shetty, 2001).
Comparing genes on chromosome Z with chromosome W showed no avian counterpart to the synteny found in chromosome X and Y. Consequently, showing no synteny within the species, therefore meaning that although they shared a common ancestor, we can see that the chromosomes have evolved and recombined; the synteny between H. sapien sex chromosomes show they originated in the same place on the same chromosome whereas the avian sex chromosomes showing no synteny, imply they are from different parts of the same chromosome.
As of yet, it is not fully clear whether the ZZ male: ZW female chromosome system works via a female determining gene on the W, or dosage variances in a gene on the Z (Graves and Shetty, 2001). However, studies of chimeric (genetically merged species) birds with a variable quantity of ZZW triploid cells showed that the occurrence of a W chromosome did have a feminizing effect, though conversely, Z dosage had a male effect (Graves and Shetty, 2001). Therefore, both dosages of a Z-borne gene or a dominant W-borne switch gene could both operate in birds to initiate sex determination. The recent identification of the previously mentioned DMRT1 gene, involved in testis differentiation in all vertebrates located on G. gallus Z, has raised speculation that this may be the 'true' sex determining gene in avian species.
X+Y vs Gallus gallus
As seen in figure 7, the H. sapien sex chromosomes map to ten (1,2,3,4,9,10,12,13,14,21) G. gallus autosomes, showing little recombination from the original ancestors. The H. sapien X shares homology with the G. gallus chromosomes 4 and 1 (Livernois et al., 2012). Graves and Shetty (2001) state that despite the differences in size and gene content between heteromorphic sex chromosomes in mammals and birds, there is strong evidence that they originally evolved from an ordinary autosomal pair in the common ancestor. This hypothesis has been put forward previously by Ohno (1967) on the basis of observations of intermediate stages in the variation of the Z and W chromosomes in different snake families. Furthermore, Ohno (1967) suggested that the snake Z chromosome preserved its original size and gene content, however, the W chromosome had degenerated gradually; In turn, this is also a conceivable theory for the avian sex chromosomes. Graves and Shetty (2001) add that the mammalian X has maintained the gene content of an original autosome similarly to the avian Z, but the Y represents a degraded artefact of its original form, comparable to the W. Comparative mapping supports this hypothesis and can demonstrate how sex chromosome differentiation in mammals and birds has occurred independently (Graves and Shetty, 2001).
It has been suggested that the mammalian Y and the avian W were fundamentally unstable due to their repetitive structure, or their low representation in the population, however this was recently disproven by the finding of greater interspecies variation in mammal Y genes than in bird W genes. This implies that the variation is essentially male-driven, more than likely due to the many mitotic divisions that the mammal Y is subjected to in the testis but not the chicken W (Graves and Shetty, 2001).
Z+W vs Homo sapien
There has been practically no gene mapping in any bird species except G. gallus. Through my research I have found that the vast majority of the genes on the G. gallus Z chromoomes map to the H. sapien chromosome 9. Graves and Shetty (2001) support my findings stating that their results show the same outcome. During the study Graves and Shetty (2001) noted that they found only four genes mapped to the small, heterochromatic chicken W chromosome, and all had homologues on the Z chromosome, once more corresponding with my findings that the genes had homologues (Figure 10) however their research delved further into the genome having been able to inspect every gene on both sex chromosomes of both species. Baverstock et al., (1982) noted that from early studies of enzyme dosage, there is no evidence of dosage compensation on chromosome Z, but recent quantification of the mRNA transcribed by Z linked genes shows distinct dosage compensation (McQueen et al., 2001). The two Z chromosomes in males replicate synchronously, implying the absence of an inactivation mechanism similar to that of X inactivation (Graves and Shetty, 2001).
The question could therefore possibly be simpler to answer by observation of the phenotypes of ZO and ZZW diploid birds, but only one has ever been described, despite extended search. Their absence suggests that, unlike mammals in which most X-borne genes are active in a single dose in both sexes, two copies of at least some W-Z shared genes are vital in birds (Graves and Shetty, 2001). The avian sex chromosomes show less rearrangement than their H. sapien counter parts, mapping only to H. sapien chromosomes, 5, 9 and 18 (figure 9).
Once more, Graves' (2001) research supports my results as it displays how the Z-borne bird candidate sex determining gene DMRT1 has a homologue in mammals that lies on human chromosome 9. Therefore, the autonomous evolution of XY and ZW sex chromosomes from different autosome pairs must have evolved from different sex determining mechanisms. Although the starting autosome pair and the sex determining allele were different, the process of sex chromosome evolution in mammals has been completely parallel in birds, involving attainment of an allele which controls a step-in gonad differentiation, inhibition of recombination around a cluster of sex specific genes, and the degradation of this non-recombining region (Graves and Shretty, 2001). The avian SOX3 gene which is homologous to mammalian SRY gene is autosomal in other avian species such as the Emu (Shetty, 2001).
Thus meaning the avian system shows further recombination from the common ancestor than H. sapien.
There are selective pressures causing the recombination of the chromosomes in birds and primates. There is a clear difference in the rate of recombination in primates and birds, with primates showing more changes to the sex chromosomes and birds showing more changes to their autosomes. Therefore implying, G. gallus shares more with the common ancestor and the H. sapien autosomes than the sex chromosomes
Conclusion
Ohno's (1967) hypothesis predicted that the Y chromosome, and all the genes on it, was derived from the original X, and that the W, and all the genes on it, was derived from the original Z over the last 200-300 million years (Graves and Shetty, 2001). Comparisons between X and Y-borne homologues, or Z and W-borne homologues may reveal changes in the structure of genes and the sequence that accompanied the acquisition of testis-specific expression and sex-specific function of SRY in mammals, and DMRT1 in birds, and help deduce how these sex-determining systems are related to each other.
The Primates X and Y are very similar except for length, while Z and W are very different and may not be homologous, but show similarities in the chromosomes that they map to, they may have once been very similar, or perhaps they were even different parts of the same chromosomes. Though I am unable to tell whether human sex chromosomes or avian autosomes have a stronger link to common ancestor, though avian has further recombination's on autosomes.
In conclusion sex chromosomes in different vertebrate groups evolved in independent ways from different regions of the conserved vertebrate genome of a common ancestor. Sex chromosomes differentiate be degradation of a male specific Y or female X. Comparisons of genomes and sex chromosomes in mammals and birds are beginning to fill in details of how dosage compensation is achieved, therefore presenting a picture of great diversity (Graves, 2016). The hypotheses of this study make predictions about the sex-linked genes in Homosapien and Gallus gallus. If the autosomal pair that became the therian X. Given how broad the subject is if I'd had more time I'd delve further into the subject, including more examples of primate and avian/reptile species in order to get a better view of the results. Whether this outcome, results are solely the results of G. gallus vs H. sapien or whether this information stands for all mammals compared to avian species sex chromosome evolution.