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Tip revision: becc7b948123f8683c49ed41480ca2682d979a7f authored by Yan Wong on 09 December 2022, 18:50:12 UTC
Update docs/mutations.md
Tip revision: becc7b9
msGCHOT.c
/* compile with gcc -o msHOT msGCHOT.c streecGCHOT.c rand1.c -lm */
/*same as ms.c but with mutliple crossover and geneconv hotspots addition */

/***** ms.c     ************************************************
*
*       Generates samples of gametes ( theta given or fixed number 
*						of segregating sites.)
*	Usage is shown by typing ms without arguments.   
        usage: ms nsam howmany  -t  theta  [options]
		or
	       ms nsam howmany -s segsites  [options] 

	   nsam is the number of gametes per sample.
	   howmany is the number of samples to produce.
	   With -t the numbers of segregating sites will randomly vary 
		from one sample to the next.
	   with -s segsites,  the number of segregating sites will be
		segsites in each sample.

           Other options: See msdoc.pdf or after downloading and compiling, type ms<CR>.


*	  Arguments of the options are explained here:

           npop:  Number of subpopulations which make up the total population
           ni:  the sample size from the i th subpopulation (all must be 
		specified.) The output will have the gametes in order such that
		the first n1 gametes are from the first island, the next n2 are
		from the second island, etc.
           nsites: number of sites between which recombination can occur.
           theta: 4No times the neutral mutation rate 
           rho: recombination rate between ends of segment times 4No
	   f: ratio of conversion rate to recombination rate. (Wiuf and Hein model.)
	   track_len:  mean length of conversion track in units of sites.  The 
		       total number of sites is nsites, specified with the -r option.
           mig_rate: migration rate: the fraction of each subpop made up of
                 migrants times 4No. 
           howmany: howmany samples to generate.

	Note:  In the above definition, No is the total diploid population if
		npop is one, otherwise, No is the diploid population size of each
		subpopulation. 
	A seed file called "seedms" will be created  if it doesn't exist. The
		seed(s) in this file will be modified by the program. 
		So subsequent runs
		will produce new output.  The initial contents of seedms will be
		printed on the second line of the output.
        Output consists of one line with the command line arguments and one
	 	line with the seed(s).
		The samples appear sequentially following that line.
		Each sample begins with "//", then the number of segregating sites, the positions
		of the segregating sites (on a scale of 0.0 - 1.0). On the following
		lines are the sampled gametes, with mutants alleles represented as
		ones and ancestral alleles as zeros.
	To compile:  cc -o ms  ms.c  streec.c  rand1.c -lm
		or:  cc -o ms ms.c streec.c rand2.c -lm
	 (Of course, gcc would be used instead of cc on some machines.  And -O3 or 
		some other optimization switches might be usefully employed with some 
		compilers.) ( rand1.c uses drand48(), whereas rand2.c uses rand() ).

*
*   Modifications made to combine ms and mss on 25 Feb 2001
*	Modifications to command line options to use switches  25 Feb 2001
*	Modifications to add // before each sample  25 Feb 2001
	Modifications to add gene conversion 5 Mar 2001
	Added demographic options -d  13 Mar 2001
	Changed ran1() to use rand(). Changed seed i/o to accomodate this change. 20 April.
	Changed cleftr() to check for zero rand() .13 June 2001
	Move seed stuff to subroutine seedit()  11 July 2001
	Modified streec.c to handle zero length demographic intervals 9 Aug 2001
	Corrected problem with negative growth rates (Thanks to D. Posada and C. Wiuf) 13 May 2002
	Changed sample_stats.c to output thetah - pi rather than pi - thetah.  March 8 2003.
	Changed many command line options, allowing arbitrary migration matrix, and subpopulation
	   sizes.  Also allows parameters to come from a file. Option to output trees.  Option to
	   split and join subpopulations.   March 8, 2003. (Old versions saved in msold.tar ).
	!!! Fixed bug in -en option.  Earlier versions may have produced garbage when -en ... used. 9 Dec 2003
	Fixed bug which resulted in incorrect results for the case where
             rho = 0.0 and gene conversion rate > 0.0. This case was not handled
	    correctly in early versions of the program. 5 Apr 2004.  (Thanks to
	    Vincent Plagnol for pointing out this problem.) 
	Fixed bug in prtree().  Earlier versions may have produced garbage when the -T option was used.
		 1 Jul 2004.
	Fixed bug in -e. options that caused problems with -f option  13 Aug 2004.
	Fixed bug in -es option, which was a problem when used with -eG. (Thanks again to V. Plagnol.) 6 Nov. 2004
	Added -F option:  -F minfreq  produces output with sites with minor allele freq < minfreq filtered out.  11 Nov. 2004.
	Fixed bug in streec.c (isseg() ).  Bug caused segmentation fault, crash on some machines. (Thanks
	    to Melissa Jane Todd-Hubisz for finding and reporting this bug.)
	Added -seeds option 4 Nov 2006
	Added "tbs" arguments feature 4 Nov 2006
***************************************************************************/


#define UN_EXTERN
#include <stdio.h>
#include <stdlib.h>
#include <math.h>
#include <assert.h>
#include <string.h>
#include "ms.h"
#include "eca_funcsHOTmulti.h"

#define SITESINC 10 

unsigned maxsites = SITESINC ;

struct node{
	int abv;
	int ndes;
	float time;
	};

struct segl {
	int beg;
	struct node *ptree;
	int next;
	};

double *posit ;
double segfac ;
int count, ntbs ;
struct params pars ;	

main(argc,argv)
        int argc;
        char *argv[];
{
	int i, k, howmany, segsites ;
	char **list, **cmatrix(), **tbsparamstrs ;
	FILE *pf, *fopen() ;
	double probss ;
	void seedit( const char * ) ;
	void getpars( int argc, char *argv[], int *howmany )  ;
	int gensam( char **list, double *probss ) ;


	ntbs = 0 ;   /* these next few lines are for reading in parameters from a file (for each sample) */
	tbsparamstrs = (char **)malloc( argc*sizeof(char *) ) ;

#ifndef SUPPRESS_OUTPUT
	for( i=0; i<argc; i++) printf("%s ",argv[i]);
#endif

	for( i =0; i<argc; i++) tbsparamstrs[i] = (char *)malloc(30*sizeof(char) ) ;
	for( i = 1; i<argc ; i++)
			if( strcmp( argv[i],"tbs") == 0 )  argv[i] = tbsparamstrs[ ntbs++] ;
	
	count=0;

	if( ntbs > 0 )  for( k=0; k<ntbs; k++)  scanf(" %s", tbsparamstrs[k] );
	getpars( argc, argv, &howmany) ;   /* results are stored in global variable, pars */
	
	if( !pars.commandlineseedflag ) seedit( "s");
	pf = stdout ;

	if( pars.mp.segsitesin ==  0 ) {
	     list = cmatrix(pars.cp.nsam,maxsites+1);
	     posit = (double *)malloc( (unsigned)( maxsites*sizeof( double)) ) ;
	}
	else {
	     list = cmatrix(pars.cp.nsam, pars.mp.segsitesin+1 ) ;
	     posit = (double *)malloc( (unsigned)( pars.mp.segsitesin*sizeof( double)) ) ;
	     if( pars.mp.theta > 0.0 ){
		    segfac = 1.0 ;
		    for(  i= pars.mp.segsitesin; i > 1; i--) segfac *= i ;
		 }
	}

#ifdef SUMMARY_STATS
    /* print out the header*/
    printf("t\tnum_trees\tre_events\tca_events\tgc_events");
    int N = pars.cp.npop;
	struct devent *event ;

    for (event = pars.cp.deventlist; event != NULL; event = event->nextde) {
        if (event->detype == 's') {
            N++;
        }
    }

    for (i = 0; i < N * N; i++) {
        printf("\tmig_events_%d", i);
    }
    printf("\tbreakpoints");
    printf("\n");
#endif

    while( howmany-count++ ) {
	   if( (ntbs > 0) && (count >1 ) ){
	         for( k=0; k<ntbs; k++){ 
			    if( scanf(" %s", tbsparamstrs[k]) == EOF ){
			       if( !pars.commandlineseedflag ) seedit( "end" );
				   exit(0);
				}
			 }
			 getpars( argc, argv, &howmany) ;
	   }
	   
#ifndef SUPPRESS_OUTPUT
       fprintf(pf,"\n//");
	   if( ntbs >0 ){
			for(k=0; k< ntbs; k++) printf("\t%s", tbsparamstrs[k] ) ;
		}
		printf("\n");
#endif
        segsites = gensam( list, &probss ) ; 
#ifndef SUPPRESS_OUTPUT
        if( (segsites > 0 ) || ( pars.mp.theta > 0.0 ) ) {
           fprintf(pf,"segsites: %d\n",segsites);
	       if( (pars.mp.segsitesin > 0 ) && ( pars.mp.theta > 0.0 )) 
		       fprintf(pf,"\nprob: %g", probss ) ;
		   if( segsites > 0 )	fprintf(pf,"\npositions: ");
		   for( i=0; i<segsites; i++)
              fprintf(pf,"%6.4lf ",posit[i] );
           fprintf(pf,"\n");
	       if( segsites > 0 ) 
	          for(i=0;i<pars.cp.nsam; i++) { fprintf(pf,"%s\n", list[i] ); }
	    }
#endif
    }
	if( !pars.commandlineseedflag ) seedit( "end" );

}



	int 
gensam( char **list, double *pprobss ) 
{
	int nsegs, h, i, k, j, seg, ns, start, end, len, segsit ;
	struct segl *seglst, *segtre_mig(struct c_params *p, int *nsegs ) ; /* used to be: [MAXSEG];  */
	double nsinv,  tseg, tt, ttime(struct node *, int nsam), ttimemf(struct node *, int nsam, int mfreq) ;
	double *pk;
	int *ss;
	int segsitesin,nsites;
	double theta, es ;
	int nsam, mfreq ;
	void prtree( struct node *ptree, int nsam);
	int make_gametes(int nsam, int mfreq,  struct node *ptree, double tt, int newsites, int ns, char **list );
 	void ndes_setup( struct node *, int nsam );


	nsites = pars.cp.nsites ;
	nsinv = 1./nsites;
	seglst = segtre_mig(&(pars.cp),  &nsegs ) ;
	
	nsam = pars.cp.nsam;
	segsitesin = pars.mp.segsitesin ;
	theta = pars.mp.theta ;
	mfreq = pars.mp.mfreq ;

	if( pars.mp.treeflag ) {
	  	ns = 0 ;
	    for( seg=0, k=0; k<nsegs; seg=seglst[seg].next, k++) {
#ifndef SUPPRESS_OUTPUT
	      if( (pars.cp.r > 0.0 ) || (pars.cp.f > 0.0) ){
		     end = ( k<nsegs-1 ? seglst[seglst[seg].next].beg -1 : nsites-1 );
		     start = seglst[seg].beg ;
		     len = end - start + 1 ;
		     fprintf(stdout,"[%d]", len);
	      }
	      prtree( seglst[seg].ptree, nsam ) ;
#endif
	      if( (segsitesin == 0) && ( theta == 0.0 ) ) 
	  	      free(seglst[seg].ptree) ;
	    }
	}

    if( (segsitesin == 0) && ( theta > 0.0)   ) {
	  ns = 0 ;
	  for( seg=0, k=0; k<nsegs; seg=seglst[seg].next, k++) { 
		if( mfreq > 1 ) ndes_setup( seglst[seg].ptree, nsam );
		end = ( k<nsegs-1 ? seglst[seglst[seg].next].beg -1 : nsites-1 );
		start = seglst[seg].beg ;
		len = end - start + 1 ;
		tseg = len*(theta/nsites) ;
		if( mfreq == 1) tt = ttime(seglst[seg].ptree, nsam);
                else tt = ttimemf(seglst[seg].ptree, nsam, mfreq );
		segsit = poisso( tseg*tt );
		if( (segsit + ns) >= maxsites ) {
			maxsites = segsit + ns + SITESINC ;
			posit = (double *)realloc(posit, maxsites*sizeof(double) ) ;
			  biggerlist(nsam, list) ; 
		}
		make_gametes(nsam,mfreq,seglst[seg].ptree,tt, segsit, ns, list );
		free(seglst[seg].ptree) ;
		locate(segsit,start*nsinv, len*nsinv,posit+ns);   
		ns += segsit;
	  }
    }
   else if( segsitesin > 0 ) {

        pk = (double *)malloc((unsigned)(nsegs*sizeof(double)));
        ss = (int *)malloc((unsigned)(nsegs*sizeof(int)));
        if( (pk==NULL) || (ss==NULL) ) perror("malloc error. gensam.2");


	  tt = 0.0 ;
	  for( seg=0, k=0; k<nsegs; seg=seglst[seg].next, k++) { 
		if( mfreq > 1 ) ndes_setup( seglst[seg].ptree, nsam );
		end = ( k<nsegs-1 ? seglst[seglst[seg].next].beg -1 : nsites-1 );
		start = seglst[seg].beg ;
		len = end - start + 1 ;
		tseg = len/(double)nsites ;
               if( mfreq == 1 ) pk[k] = ttime(seglst[seg].ptree,nsam)*tseg ;
               else pk[k] = ttimemf(seglst[seg].ptree,nsam, mfreq)*tseg ;
                 tt += pk[k] ;
	  }
	  if( theta > 0.0 ) { 
	    es = theta * tt ;
	    *pprobss = exp( -es )*pow( es, (double) segsitesin) / segfac ;
	  }
	  if( tt > 0.0 ) {
          for (k=0;k<nsegs;k++) pk[k] /= tt ;
          mnmial(segsitesin,nsegs,pk,ss);
	  }
	  else
            for( k=0; k<nsegs; k++) ss[k] = 0 ;
	  ns = 0 ;
	  for( seg=0, k=0; k<nsegs; seg=seglst[seg].next, k++) { 
		 end = ( k<nsegs-1 ? seglst[seglst[seg].next].beg -1 : nsites-1 );
		 start = seglst[seg].beg ;
		 len = end - start + 1 ;
		 tseg = len/(double)nsites;
		 make_gametes(nsam,mfreq,seglst[seg].ptree,tt*pk[k]/tseg, ss[k], ns, list);

		 free(seglst[seg].ptree) ;
		 locate(ss[k],start*nsinv, len*nsinv,posit+ns);   
		 ns += ss[k] ;
	  }
	  free(pk);
	  free(ss);

    }
	for(i=0;i<nsam;i++) list[i][ns] = '\0' ;
	return( ns ) ;
}

	void 
ndes_setup(struct node *ptree, int nsam )
{
	int i ;

	for( i=0; i<nsam; i++) (ptree+i)->ndes = 1 ;
	for( i = nsam; i< 2*nsam -1; i++) (ptree+i)->ndes = 0 ;
	for( i= 0; i< 2*nsam -2 ; i++)  (ptree+((ptree+i)->abv))->ndes += (ptree+i)->ndes ;

}

	int
biggerlist(nsam,  list )
	int nsam ;
	char ** list ;
{
	int i;

/*  fprintf(stderr,"maxsites: %d\n",maxsites);  */	
	for( i=0; i<nsam; i++){
	   list[i] = (char *)realloc( list[i],maxsites*sizeof(char) ) ;
	   if( list[i] == NULL ) perror( "realloc error. bigger");
	   }
}
	   


/* allocates space for gametes (character strings) */
	char **
cmatrix(nsam,len)
	int nsam, len;
{
	int i;
	char **m;

	if( ! ( m = (char **) malloc( (unsigned) nsam*sizeof( char* ) ) ) )
	   perror("alloc error in cmatrix") ;
	for( i=0; i<nsam; i++) {
		if( ! ( m[i] = (char *) malloc( (unsigned) len*sizeof( char ) )))
			perror("alloc error in cmatric. 2");
		}
	return( m );
}



	int
locate(n,beg,len,ptr)
	int n;
	double beg, len, *ptr;
{
	int i;

	ordran(n,ptr);
	for(i=0; i<n; i++)
		ptr[i] = beg + ptr[i]*len ;

}


  void
getpars(int argc, char *argv[], int *phowmany )
{
	int arg, i, j, sum , pop , argstart, npop , npop2, pop2 ;
	double migr, mij, psize, palpha ;
	//struct params p;
	void addtoelist( struct devent *pt, struct devent *elist ); 
	void argcheck( int arg, int argc, char ** ), commandlineseed( char ** ) ;
	void free_eventlist( struct devent *pt, int npop );
	struct devent *ptemp , *pt ;
	FILE *pf ;
	char ch3 ;
	

  if( count == 0 ) {
	if( argc < 4 ){ fprintf(stderr,"Too few command line arguments\n"); usage();}
	pars.cp.nsam = atoi( argv[1] );
	if( pars.cp.nsam <= 0 ) { fprintf(stderr,"First argument error. nsam <= 0. \n"); usage();}
	*phowmany = atoi( argv[2] );
	if( *phowmany  <= 0 ) { fprintf(stderr,"Second argument error. howmany <= 0. \n"); usage();}
	pars.commandlineseedflag = 0 ;
	pars.cp.r = pars.mp.theta =  pars.cp.f = 0.0 ;
	pars.cp.track_len = 0. ;
	pars.cp.npop = npop = 1 ;
	pars.cp.mig_mat = (double **)malloc( (unsigned) sizeof( double *) );
	pars.cp.mig_mat[0] = (double *)malloc( (unsigned)sizeof(double *));
	pars.cp.mig_mat[0][0] =  0.0 ;
	pars.mp.segsitesin = 0 ;
	pars.mp.treeflag = 0 ;
        pars.mp.mfreq = 1 ;
	pars.cp.config = (int *) malloc( (unsigned)(( pars.cp.npop +1 ) *sizeof( int)) );
	(pars.cp.config)[0] = pars.cp.nsam ;
	pars.cp.size= (double *) malloc( (unsigned)( pars.cp.npop *sizeof( double )) );
	(pars.cp.size)[0] = 1.0  ;
	pars.cp.alphag = (double *) malloc( (unsigned)(( pars.cp.npop ) *sizeof( double )) );
	(pars.cp.alphag)[0] = 0.0  ;
	pars.cp.nsites = 2 ;
  }
  else{
	npop = pars.cp.npop ;
	free_eventlist( pars.cp.deventlist, npop );
  }
  	pars.cp.deventlist = NULL ;

	/*  Eric's stuff for hotspots and ascertainment -- initializations */
	gNumHotSpots = 0;
	//gHotSpots = NULL;
	//gHSRates = NULL;
	gHSRates = NULL;
	gHotSpotStart = NULL;
	gHotSpotEnd = NULL;

	gNumHotSpotsGC = 0;
	gHSRatesGC = NULL;
	gHotSpotStartGC = NULL;
	gHotSpotEndGC = NULL;

	arg = 3 ;

	while( arg < argc ){
		if( argv[arg][0] != '-' ) { fprintf(stderr," argument should be -%s ?\n", argv[arg]); usage();}
		switch ( argv[arg][1] ){
			case 'f' :
				if( ntbs > 0 ) { fprintf(stderr," can't use tbs args and -f option.\n"); exit(1); }
				arg++;
				argcheck( arg, argc, argv);
				pf = fopen( argv[arg], "r" ) ;
				if( pf == NULL ) {fprintf(stderr," no parameter file %s\n", argv[arg] ); exit(0);}
				arg++;
				argc++ ;
				argv = (char **)malloc(  (unsigned)(argc+1)*sizeof( char *) ) ;
				argv[arg] = (char *)malloc( (unsigned)(20*sizeof( char )) ) ;
				argstart = arg ;
				while( fscanf(pf," %s", argv[arg]) != EOF ) {
					arg++;
					argc++;
					argv = (char **)realloc( argv, (unsigned)argc*sizeof( char*) ) ;
				        argv[arg] = (char *)malloc( (unsigned)(20*sizeof( char )) ) ;
					}
				fclose(pf);
				argc--;
				arg = argstart ;
				break;
			case 'r' : 
				arg++;
				argcheck( arg, argc, argv);
				pars.cp.r = atof(  argv[arg++] );
				argcheck( arg, argc, argv);
				pars.cp.nsites = atoi( argv[arg++]);
				if( pars.cp.nsites <2 ){
					fprintf(stderr,"with -r option must specify both rec_rate and nsites>1\n");
					usage();
					}
				break;		
			case 'c' : 
				arg++;
				argcheck( arg, argc, argv);
				pars.cp.f = atof(  argv[arg++] );
				argcheck( arg, argc, argv);
				pars.cp.track_len = atof( argv[arg++]);
				if( pars.cp.track_len <1. ){
					fprintf(stderr,"with -c option must specify both f and track_len>0\n");
					usage();
					}
				break;		
			case 't' : 
				arg++;
				argcheck( arg, argc, argv);
				pars.mp.theta = atof(  argv[arg++] );
				break;
			case 's' : 
				arg++;
				argcheck( arg, argc, argv);
				if( argv[arg-1][2] == 'e' ){  /* command line seeds */
					pars.commandlineseedflag = 1 ;
					if( count == 0 ) commandlineseed(argv+arg );
					arg += 3 ;
				}
				else {
				    pars.mp.segsitesin = atoi(  argv[arg++] );
				}
				break;
			case 'F' : 
				arg++;
				argcheck( arg, argc, argv);
				pars.mp.mfreq = atoi(  argv[arg++] );
                                if( (pars.mp.mfreq < 2 ) || (pars.mp.mfreq > pars.cp.nsam/2 ) ){
                                    fprintf(stderr," mfreq must be >= 2 and <= nsam/2.\n");
                                    usage();
                                    }
				break;
			case 'T' : 
				pars.mp.treeflag = 1 ;
				arg++;
				break;
			case 'I' : 
				arg++;
			    if( count == 0 ) {
				    argcheck( arg, argc, argv);
					pars.cp.npop = atoi( argv[arg]);
			        pars.cp.config = (int *) realloc( pars.cp.config, (unsigned)( pars.cp.npop*sizeof( int)));
				    npop = pars.cp.npop ;
				}
			    arg++;
				for( i=0; i< pars.cp.npop; i++) {
				   argcheck( arg, argc, argv);
				   pars.cp.config[i] = atoi( argv[arg++]);
				   }
				if( count == 0 ){
				   pars.cp.mig_mat = (double **)realloc(pars.cp.mig_mat, (unsigned)(pars.cp.npop*sizeof(double *) )) ;
				   for(i=0; i<pars.cp.npop; i++) pars.cp.mig_mat[i] = (double *)realloc(pars.cp.mig_mat[i],
					   (unsigned)( pars.cp.npop*sizeof(double)));
				   pars.cp.size = (double *) realloc( pars.cp.size, (unsigned)( pars.cp.npop*sizeof( double )));
				   pars.cp.alphag = (double *) realloc( pars.cp.alphag, (unsigned)( pars.cp.npop*sizeof( double )));
				}
				for( i=1; i< pars.cp.npop ; i++) {
					 (pars.cp.size)[i] = (pars.cp.size)[0]  ;
					(pars.cp.alphag)[i] = (pars.cp.alphag)[0] ;
				}
				if( (arg <argc) && ( argv[arg][0] != '-' ) ) {
				  argcheck( arg, argc, argv);
				  migr = atof(  argv[arg++] );
				}
				else migr = 0.0 ;
				for( i=0; i<pars.cp.npop; i++) 
				    for( j=0; j<pars.cp.npop; j++) pars.cp.mig_mat[i][j] = migr/(pars.cp.npop-1) ;
				for( i=0; i< pars.cp.npop; i++) pars.cp.mig_mat[i][i] = migr ;
				break;
			case 'm' :
			     if( npop < 2 ) { fprintf(stderr,"Must use -I option first.\n"); usage();}
			     if( argv[arg][2] == 'a' ) {
				    arg++;
				    for( pop = 0; pop <npop; pop++)
				      for( pop2 = 0; pop2 <npop; pop2++){
					     argcheck( arg, argc, argv);
					     pars.cp.mig_mat[pop][pop2]= atof( argv[arg++] ) ;
					  }
				    for( pop = 0; pop < npop; pop++) {
					  pars.cp.mig_mat[pop][pop] = 0.0 ;
					  for( pop2 = 0; pop2 < npop; pop2++){
					    if( pop2 != pop ) pars.cp.mig_mat[pop][pop] += pars.cp.mig_mat[pop][pop2] ;
					  }
				    }	
				}
			    else {
		             arg++;
			         argcheck( arg, argc, argv);
		             i = atoi( argv[arg++] ) -1;
			         argcheck( arg, argc, argv);
		             j = atoi( argv[arg++] ) -1;
			         argcheck( arg, argc, argv);
		             mij = atof( argv[arg++] );
		             pars.cp.mig_mat[i][i] += mij -  pars.cp.mig_mat[i][j]  ;
		             pars.cp.mig_mat[i][j] = mij;
			    }
				break;
			case 'v' :  /* case added by Eric Anderson to allow specification of recombinational
							hotspots of different intensities  */
				arg++;
			        argcheck( arg, argc, argv);
				gNumHotSpots = atoi(argv[arg++]);
				gHotSpotStart = (int *)calloc((size_t)gNumHotSpots, sizeof(int));
				gHotSpotEnd = (int *)calloc((size_t)gNumHotSpots, sizeof(int));
				gHSRates = (double *)calloc((size_t)gNumHotSpots, sizeof(double));

				for (i = 0; i<gNumHotSpots; i++)
				  {
				    argcheck( arg, argc, argv);
				    gHotSpotStart[i] = atoi(argv[arg++]);
				    gHotSpotStart[i] = gHotSpotStart[i]-1;
				    argcheck( arg, argc, argv);
				    gHotSpotEnd[i] = atoi(argv[arg++]);
				    gHotSpotEnd[i] = gHotSpotEnd[i]-1;
				    argcheck( arg, argc, argv);
				    gHSRates[i] = atof(argv[arg++]);
				    //printf("\n\n%d\n\n",p.cp.nsites);
				    if ((gHotSpotStart[i] < 0) || (gHotSpotEnd[i] >= pars.cp.nsites))
			             {
				        fprintf(stderr,"\n\n At least one crossover hotspot is not contained within the sequence. Exiting....\n\n");
					usage();
				     }
				    if(i>0 && gHotSpotStart[i]<=gHotSpotEnd[i-1])  
				      {
					fprintf(stderr,"\n\nHot spots overlapping or not listed in order.  Abort!...\n\n");
					usage();
				      }
				    if(gHotSpotStart[i] >= gHotSpotEnd[i])
				      {
					fprintf(stderr,"\n\nHotspot locations entered incorrectly.\n\n");
				 	usage();
                                      }
				  }
				break;
			case 'V' :  /* case added by GRH to allow specification of a single gene conversion hotspot of specified intensity in specified area*/
				arg++;
			        argcheck( arg, argc, argv);
				gNumHotSpotsGC = atoi(argv[arg++]);
				gHotSpotStartGC = (int *)calloc((size_t)gNumHotSpotsGC, sizeof(int));
				gHotSpotEndGC = (int *)calloc((size_t)gNumHotSpotsGC, sizeof(int));
				gHSRatesGC = (double *)calloc((size_t)gNumHotSpotsGC, sizeof(double));

				for (i = 0; i<gNumHotSpotsGC; i++)
				  {
			            argcheck( arg, argc, argv);
				    gHotSpotStartGC[i] = atoi(argv[arg++]);
				    gHotSpotStartGC[i] = gHotSpotStartGC[i]-1;
			            argcheck( arg, argc, argv);
				    gHotSpotEndGC[i] = atoi(argv[arg++]);
				    gHotSpotEndGC[i] = gHotSpotEndGC[i]-1;
			            argcheck( arg, argc, argv);
				    gHSRatesGC[i] = atof(argv[arg++]);
                                    if ((gHotSpotStartGC[i] < 0) || (gHotSpotEndGC[i] >= pars.cp.nsites))
			             { 
                                       fprintf(stderr,"\n\n At least one gene conversion hotspot is not contained within the sequence. Exiting....\n\n");
  	                               usage();
                                     }
				    if(i>0 && gHotSpotStartGC[i]<=gHotSpotEndGC[i-1])  
				      {
					fprintf(stderr,"\n\nGene Conv Hot spots overlapping or not listed in order.  Abort!...\n\n");
					usage();
				      }
                                    if(gHotSpotStartGC[i] >= gHotSpotEndGC[i])
                                      {
                                        fprintf(stderr,"\n\nHotspot locations entered incorrectly.\n\n");
					usage();
                                      }
				  }
				break;
			case 'n' :
			     if( npop < 2 ) { fprintf(stderr,"Must use -I option first.\n"); usage();}
			    arg++;
			    argcheck( arg, argc, argv);
			    pop = atoi( argv[arg++] ) -1;
			    argcheck( arg, argc, argv);
			    psize = atof( argv[arg++] );
			    pars.cp.size[pop] = psize ;
			   break;
			case 'g' :
			     if( npop < 2 ) { fprintf(stderr,"Must use -I option first.\n"); usage();}
			    arg++;
			    argcheck( arg, argc, argv);
			    pop = atoi( argv[arg++] ) -1;
			    if( arg >= argc ) { fprintf(stderr,"Not enough arg's after -G.\n"); usage(); }
			    palpha = atof( argv[arg++] );
			    pars.cp.alphag[pop] = palpha ;
			   break;
			case 'G' :
			    arg++;
			    if( arg >= argc ) { fprintf(stderr,"Not enough arg's after -G.\n"); usage(); }
			    palpha = atof( argv[arg++] );
			    for( i=0; i<pars.cp.npop; i++) 
			       pars.cp.alphag[i] = palpha ;
			   break;
			case 'e' :
			    pt = (struct devent *)malloc( sizeof( struct devent) ) ;
			    pt->detype = argv[arg][2] ;
			    ch3 = argv[arg][3] ;
			    arg++;
			    argcheck( arg, argc, argv);
			    pt->time = atof( argv[arg++] ) ;
			    pt->nextde = NULL ;
			    if( pars.cp.deventlist == NULL ) 
				    pars.cp.deventlist = pt ;
			    else if ( pt->time < pars.cp.deventlist->time ) { 
				    ptemp = pars.cp.deventlist ;
				    pars.cp.deventlist = pt ;
				    pt->nextde = ptemp ;	
				}	
			    else
				   addtoelist( pt, pars.cp.deventlist ) ;
			    switch( pt->detype ) {
				case 'N' :
			          argcheck( arg, argc, argv);
				      pt->paramv = atof( argv[arg++] ) ;
				      break;
				case 'G' :
				  if( arg >= argc ) { fprintf(stderr,"Not enough arg's after -eG.\n"); usage(); }
				  pt->paramv = atof( argv[arg++] ) ;
				  break;
				case 'M' :
				    argcheck( arg, argc, argv);
				    pt->paramv = atof( argv[arg++] ) ;
				    break;
				case 'n' :
			          argcheck( arg, argc, argv);
				  pt->popi = atoi( argv[arg++] ) -1 ;
			          argcheck( arg, argc, argv);
				  pt->paramv = atof( argv[arg++] ) ;
				  break;
				case 'g' :
			          argcheck( arg, argc, argv);
				  pt->popi = atoi( argv[arg++] ) -1 ;
				  if( arg >= argc ) { fprintf(stderr,"Not enough arg's after -eg.\n"); usage(); }
				  pt->paramv = atof( argv[arg++] ) ;
				  break;
				case 's' :
			          argcheck( arg, argc, argv);
				  pt->popi = atoi( argv[arg++] ) -1 ;
			          argcheck( arg, argc, argv);
				  pt->paramv = atof( argv[arg++] ) ;
				  break;
				case 'm' :
				  if( ch3 == 'a' ) {
				     pt->detype = 'a' ;
					 argcheck( arg, argc, argv);
				     npop2 = atoi( argv[arg++] ) ;
				     pt->mat = (double **)malloc( (unsigned)npop2*sizeof( double *) ) ;
				     for( pop =0; pop <npop2; pop++){
					   (pt->mat)[pop] = (double *)malloc( (unsigned)npop2*sizeof( double) );
					   for( i=0; i<npop2; i++){
					     if( i == pop ) arg++;
					     else {
				           argcheck( arg, argc, argv); 
					       (pt->mat)[pop][i] = atof( argv[arg++] ) ;
					     }
					   }
				     }
				     for( pop = 0; pop < npop2; pop++) {
					    (pt->mat)[pop][pop] = 0.0 ;
					    for( pop2 = 0; pop2 < npop2; pop2++){
					       if( pop2 != pop ) (pt->mat)[pop][pop] += (pt->mat)[pop][pop2] ;
					    }
				     }	
				  }
				  else {
			            argcheck( arg, argc, argv);
				        pt->popi = atoi( argv[arg++] ) -1 ;
			            argcheck( arg, argc, argv);
				        pt->popj = atoi( argv[arg++] ) -1 ;
			            argcheck( arg, argc, argv);
				        pt->paramv = atof( argv[arg++] ) ;
				  }
				  break;
				case 'j' :
			          argcheck( arg, argc, argv);
				  pt->popi = atoi( argv[arg++] ) -1 ;
			          argcheck( arg, argc, argv);
				  pt->popj = atoi( argv[arg++] ) -1 ;
				  break;
				default: fprintf(stderr,"e event\n");  usage();
			    }
			 break;
			default: fprintf(stderr," option default\n");  usage() ;
			}
		}
		if( (pars.mp.theta == 0.0) && ( pars.mp.segsitesin == 0 ) && ( pars.mp.treeflag == 0 ) ) {
			fprintf(stderr," either -s or -t or -T option must be used. \n");
			usage();
			exit(1);
			}
		sum = 0 ;
		for( i=0; i< pars.cp.npop; i++) sum += (pars.cp.config)[i] ;
		if( sum != pars.cp.nsam ) {
			fprintf(stderr," sum sample sizes != nsam\n");
			usage();
			exit(1);
			}
}


	void
argcheck( int arg, int argc, char *argv[] )
{
	if( (arg >= argc ) || ( argv[arg][0] == '-') ) {
	   fprintf(stderr,"not enough arguments after %s\n", argv[arg-1] ) ;
	   fprintf(stderr,"For usage type: ms<return>\n");
	   exit(0);
	  }
}
	
	int
usage()
{
fprintf(stderr,"usage: ms nsam howmany \n");
fprintf(stderr,"  Options: \n"); 
fprintf(stderr,"\t -t theta   (this option and/or the next must be used. Theta = 4*N0*u )\n");
fprintf(stderr,"\t -s segsites   ( fixed number of segregating sites)\n");
fprintf(stderr,"\t -T          (Output gene tree.)\n");
fprintf(stderr,"\t -F minfreq     Output only sites with freq of minor allele >= minfreq.\n");
fprintf(stderr,"\t -r rho nsites     (rho here is 4Nc)\n");
fprintf(stderr,"\t\t -c f track_len   (f = ratio of conversion rate to rec rate. tracklen is mean length.) \n");
fprintf(stderr,"\t\t\t if rho = 0.,  f = 4*N0*g, with g the gene conversion rate.\n"); 
fprintf(stderr,"\t -G alpha  ( N(t) = N0*exp(-alpha*t) .  alpha = -log(Np/Nr)/t\n");      
fprintf(stderr,"\t -I npop n1 n2 ... [mig_rate] (all elements of mig matrix set to mig_rate/(npop-1) \n");    
fprintf(stderr,"\t\t -m i j m_ij    (i,j-th element of mig matrix set to m_ij.)\n"); 
fprintf(stderr,"\t\t -ma m_11 m_12 m_13 m_21 m_22 m_23 ...(Assign values to elements of migration matrix.)\n"); 
fprintf(stderr,"\t\t -n i size_i   (popi has size set to size_i*N0 \n");
fprintf(stderr,"\t\t -g i alpha_i  (If used must appear after -M option.)\n"); 
fprintf(stderr,"\t   The following options modify parameters at the time 't' specified as the first argument:\n");
fprintf(stderr,"\t -eG t alpha  (Modify growth rate of all pop's.)\n");     
fprintf(stderr,"\t -eg t i alpha_i  (Modify growth rate of pop i.) \n");    
fprintf(stderr,"\t -eM t mig_rate   (Modify the mig matrix so all elements are mig_rate/(npop-1)\n"); 
fprintf(stderr,"\t -em t i j m_ij    (i,j-th element of mig matrix set to m_ij at time t )\n"); 
fprintf(stderr,"\t -ema t npop  m_11 m_12 m_13 m_21 m_22 m_23 ...(Assign values to elements of migration matrix.)\n");  
fprintf(stderr,"\t -eN t size  (Modify pop sizes. New sizes = size*N0 ) \n");    
fprintf(stderr,"\t -en t i size_i  (Modify pop size of pop i.  New size of popi = size_i*N0 .)\n");
fprintf(stderr,"\t -es t i proportion  (Split: pop i -> pop-i + pop-npop, npop increases by 1.\n");    
fprintf(stderr,"\t\t proportion is probability that each lineage stays in pop-i. (p, 1-p are admixt. proport.\n");
fprintf(stderr,"\t\t Size of pop npop is set to N0 and alpha = 0.0 , size and alpha of pop i are unchanged.\n");
fprintf(stderr,"\t -ej t i j   ( Join lineages in pop i and pop j into pop j\n");
fprintf(stderr,"\t\t  size, alpha and M are unchanged.\n");  
fprintf(stderr,"\t -v J a_1 b_1 I_1 ... a_J b_J I_J  ( Incorporate J crossover hotspots, each of intensity I_j on [a_j,b_j] )\n");
fprintf(stderr,"\t -V K a_1 b_1 I_1 ... a_K b_K I_K  ( Incorporate K gene conversion hotspots, each of intensity I_k on [a_k,b_k] )\n");
fprintf(stderr,"\t  -f filename     ( Read command line arguments from file filename.)\n");  
fprintf(stderr," See msdoc.pdf for explanation of these parameters.\n");

exit(1);
}
	void
addtoelist( struct devent *pt, struct devent *elist ) 
{
	struct devent *plast, *pevent, *ptemp  ;

	pevent = elist ;
	while(  (pevent != NULL ) && ( pevent->time <= pt->time ) )  {
		plast = pevent ;
		pevent = pevent->nextde ;
		}
	ptemp = plast->nextde ;
	plast->nextde = pt ;
	pt->nextde = ptemp ;
}

	void 
free_eventlist( struct devent *pt, int npop )
{
   struct devent *next ;
   int pop ;
   
   while( pt != NULL){
	  next = pt->nextde ;
	  if( pt->detype == 'a' ) {
	     for( pop = 0; pop < npop; pop++) free( (pt->mat)[pop] );
		 free( pt->mat );
	  }
	  free(pt);
	  pt = next ;
   }
}

	
/************ make_gametes.c  *******************************************
*
*
*****************************************************************************/

#define STATE1 '1'
#define STATE2 '0'

	int
make_gametes(int nsam, int mfreq, struct node *ptree, double tt, int newsites, int ns, char **list )
{
	int  tip, j,  node ;
        int pickb(int nsam, struct node *ptree, double tt), 
            pickbmf(int nsam, int mfreq, struct node *ptree, double tt) ;

	for(  j=ns; j< ns+newsites ;  j++ ) {
		if( mfreq == 1 ) node = pickb(  nsam, ptree, tt);
		else node = pickbmf(  nsam, mfreq, ptree, tt);
		for( tip=0; tip < nsam ; tip++) {
		   if( tdesn(ptree, tip, node) ) list[tip][j] = STATE1 ;
		   else list[tip][j] = STATE2 ;
		   }
		}
}


/***  ttime.c : Returns the total time in the tree, *ptree, with nsam tips. **/

	double
ttime( ptree, nsam)
	struct node *ptree;
	int nsam;
{
	double t;
	int i;

	t = (ptree + 2*nsam-2) -> time ;
	for( i=nsam; i< 2*nsam-1 ; i++)
		t += (ptree + i)-> time ;
	return(t);
}


	double
ttimemf( ptree, nsam, mfreq)
	struct node *ptree;
	int nsam, mfreq;
{
	double t;
	int i;

	t = 0. ;
	for( i=0;  i< 2*nsam-2  ; i++)
	  if( ( (ptree+i)->ndes >= mfreq )  && ( (ptree+i)->ndes <= nsam-mfreq) )
		t += (ptree + (ptree+i)->abv )->time - (ptree+i)->time ;
	return(t);
}


	void
prtree( ptree, nsam)
	struct node *ptree;
	int nsam;
{
	double t;
	int i, *descl, *descr ;
	void parens( struct node *ptree, int *descl, int *descr, int noden );

	descl = (int *)malloc( (unsigned)(2*nsam-1)*sizeof( int) );
	descr = (int *)malloc( (unsigned)(2*nsam-1)*sizeof( int) );
	for( i=0; i<2*nsam-1; i++) descl[i] = descr[i] = -1 ;
	for( i = 0; i< 2*nsam-2; i++){
	  if( descl[ (ptree+i)->abv ] == -1 ) descl[(ptree+i)->abv] = i ;
	  else descr[ (ptree+i)->abv] = i ;
	 }
	parens( ptree, descl, descr, 2*nsam-2);
	free( descl ) ;
	free( descr ) ;
}

	void
parens( struct node *ptree, int *descl, int *descr,  int noden)
{
	double time ;

   if( descl[noden] == -1 ) {
	printf("%d:%5.3lf", noden+1, (ptree+ ((ptree+noden)->abv))->time );
	}
   else{
	printf("(");
	parens( ptree, descl,descr, descl[noden] ) ;
	printf(",");
	parens(ptree, descl, descr, descr[noden] ) ;
	if( (ptree+noden)->abv == 0 ) printf(");\n"); 
	else {
	  time = (ptree + (ptree+noden)->abv )->time - (ptree+noden)->time ;
	  printf("):%5.3lf", time );
	  }
        }
}

/***  pickb : returns a random branch from the tree. The probability of picking
              a particular branch is proportional to its duration. tt is total
	      time in tree.   ****/

	int
pickb(nsam, ptree, tt)
	int nsam;
	struct node *ptree;
	double tt;
{
	double x, y, ran1();
	int i;

	x = ran1()*tt;
	for( i=0, y=0; i < 2*nsam-2 ; i++) {
		y += (ptree + (ptree+i)->abv )->time - (ptree+i)->time ;
		if( y >= x ) return( i ) ;
		}
	return( i );
}

	int
pickbmf(nsam, mfreq, ptree, tt )
	int nsam, mfreq;
	struct node *ptree;
	double tt;
{
	double x, y, ran1();
	int i;

	x = ran1()*tt;
	for( i=0, y=0; i < 2*nsam-2 ; i++) {
	  if( ( (ptree+i)->ndes >= mfreq )  && ( (ptree+i)->ndes <= nsam-mfreq) )
		y += (ptree + (ptree+i)->abv )->time - (ptree+i)->time ;
	  if( y >= x ) return( i ) ;
	}
	return( i );
}

/****  tdesn : returns 1 if tip is a descendant of node in *ptree, otherwise 0. **/

	int
tdesn(ptree, tip, node )
	struct node *ptree;
	int tip, node;
{
	int k;

	for( k= tip ; k < node ; k = (ptree+k)->abv ) ;
	if( k==node ) return(1);
	else return(0);
}


/* pick2()  */

	int
pick2(n,i,j)
	int n, *i, *j;
{
	double ran1();

	*i = n * ran1() ;
	while( ( *j = n * ran1() ) == *i )
		;
	return(0) ;
}

/**** ordran.c  ***/

	int
ordran(n,pbuf)
	int n;
	double pbuf[];
{
	ranvec(n,pbuf);
	order(n,pbuf);
	return;
}


	int
mnmial(n,nclass,p,rv)
	int n, nclass, rv[];
	double p[];
{
	double ran1();
	double x, s;
	int i, j;

	for(i=0; i<nclass; i++) rv[i]=0;
	for(i=0; i<n ; i++) {
	   x = ran1();
	   j=0;
	   s = p[0];
	   while( (x > s) && ( j<(nclass-1) ) )  s += p[++j];
	   rv[j]++;
	   }
	return(j);
}

        int
order(n,pbuf)
        int n;
        double pbuf[];
{
        int gap, i, j;
        double temp;

        for( gap= n/2; gap>0; gap /= 2)
           for( i=gap; i<n; i++)
                for( j=i-gap; j>=0 && pbuf[j]>pbuf[j+gap]; j -=gap) {
                   temp = pbuf[j];
                   pbuf[j] = pbuf[j+gap];
                   pbuf[j+gap] = temp;
                   }
}


	int
ranvec(n,pbuf)
	int n;
	double pbuf[];
{
	int i;
	double ran1();

	for(i=0; i<n; i++)
		pbuf[i] = ran1();

	return;
}



	int
poisso(u)
	double u;
{
	double  cump, ru, ran1(), p, gasdev() ;
	int i=1;

	if( u > 30. ) return( (int)(0.5 + gasdev(u,u)) );
	ru = ran1();
	p = exp(-u);
	if( ru < p) return(0);
	cump = p;
	
	while( ru > ( cump += (p *= u/i ) ) )
		i++;
	return(i);
}


/* a slight modification of crecipes version */

double gasdev(m,v)
	double m, v;
{
	static int iset=0;
	static float gset;
	float fac,r,v1,v2;
	double ran1();

	if  (iset == 0) {
		do {
			v1=2.0*ran1()-1.0;
			v2=2.0*ran1()-1.0;
			r=v1*v1+v2*v2;
		} while (r >= 1.0);
		fac=sqrt(-2.0*log(r)/r);
		gset= v1*fac;
		iset=1;
		return( m + sqrt(v)*v2*fac);
	} else {
		iset=0;
		return( m + sqrt(v)*gset ) ;
	}
}

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